3D Bioplotter Research Papers

Displaying all papers about PCL (84 results)

Additive manufacturing and tissue engineering to improve outcomes in breast reconstructive surgery

Workshop on Metrology for Industry 4.0 and IoT (MetroInd4.0&IoT) 2019 Pages 38 - 42

Many women with early breast cancer undergo mastectomy as a consequence of an unfavorable tumor/breast ratio or because they prefer this option to breast conservation. As reported, breast reconstruction offers significant psychological advantages. Several techniques are currently available for the breast oncoplastic surgeon and offer interesting results in terms of aesthetic and patient-reported outcomes, using both breast implants and autologous tissues. On the other hand, advanced methodologies and technologies, such as reverse engineering and additive manufacturing, allow the development of customized porous scaffolds with tailored architectures, biological, mechanical and mass transport properties. Accordingly, the current research dealt with challenges, design…

Suturable regenerated silk fibroin scaffold reinforced with 3D-printed polycaprolactone mesh: biomechanical performance and subcutaneous implantation

Journal of Materials Science: Materials in Medicine 2019 Volume 30, Article 63

The menisci have crucial roles in the knee, chondroprotection being the primary. Meniscus repair or substitution is favored in the clinical management of the meniscus lesions with given indications. The outstanding challenges with the meniscal scaffolds include the required biomechanical behavior and features. Suturability is one of the prerequisites for both implantation and implant survival. Therefore, we proposed herein a novel highly interconnected suturable porous scaffolds from regenerated silk fibroin that is reinforced with 3D-printed polycaprolactone (PCL) mesh in the middle, on the transverse plane to enhance the suture-holding capacity. Results showed that the reinforcement of the silk fibroin scaffolds…

3D Printing of Tissue Engineering Scaffolds with Horizontal Pore and Composition Gradients

Tissue Engineering Part C: Methods 2019

This work investigated a new 3D-printing methodology to prepare porous scaffolds containing horizontal pore and composition gradients. To achieve that, a multimaterial printing technology developed in our laboratory was adapted to incorporate pore gradients. Fibers were printed by welding segments with unique material compositions and fiber diameters. Particularly, we focused on the preparation of model composite poly(ε-caprolactone)-based scaffolds with radial gradients of particulate hydroxyapatite (HA) content (higher concentrations in the outer region of the scaffold) and porosity (higher in the inner region). The morphology of the scaffolds revealed that the methodology allowed the fabrication of discrete regions with compressive mechanical…

Osteostatin potentiates the bioactivity of mesoporous glass scaffolds containing Zn2+ ions in human mesenchymal stem cells

Acta Biomaterialia 2019

There is an urgent need of biosynthetic bone grafts with enhanced osteogenic capacity. In this study, we describe the design of hierarchical meso-macroporous 3D-scaffolds based on mesoporous bioactive glasses (MBGs), enriched with the peptide osteostatin and Zn2+ ions, and their osteogenic effect on human mesenchymal stem cells (hMSCs) as a preclinical strategy in bone regeneration. The MBG compositions investigated were 80%SiO2–15%CaO–5%P2O5 (in mol-%) Blank (BL), and two analogous glasses containing 4% ZnO (4ZN) and 5% ZnO (5ZN). By using additive fabrication techniques, scaffolds exhibiting hierarchical porosity: mesopores (around 4 nm), macropores (1–600 μm) and big channels (∼1000 μm), were prepared. These MBG scaffolds…

3D Bioprinted Scaffolds Containing Viable Macrophages and Antibiotics Promote Clearance of Staphylococcus aureus Craniotomy-Associated Biofilm Infection

ACS Apllied Materials & Interfaces 2019 Volume 11, Issue 13, Pages 12298-12307

Craniotomy involves the removal of a skull fragment to access the brain, such as during tumor or epilepsy surgery, which is immediately replaced intraoperatively. The infection incidence after craniotomy ranges from 0.8 to 3%, with approximately half caused by Staphylococcus aureus (S. aureus). To mitigate infectious complications following craniotomy, we engineered a three-dimensional (3D) bioprinted bone scaffold to harness the potent antibacterial activity of macrophages (MΦs) together with antibiotics using a mouse S. aureus craniotomy-associated biofilm model that establishes a persistent infection on the bone flap, subcutaneous galea, and brain. The 3D scaffold contained rifampin and daptomycin printed in a…

Fabrication and mechanical characterization of 3D printed vertical uniform and gradient scaffolds for bone and osteochondral tissue engineering

Acta Biomaterialia 2019

Recent developments in 3D printing (3DP) research have led to a variety of scaffold designs and techniques for osteochondral tissue engineering; however, the simultaneous incorporation of multiple types of gradients within the same construct remains a challenge. Herein, we describe the fabrication and mechanical characterization of porous poly(ε-caprolactone) (PCL) and PCL-hydroxyapatite (HA) scaffolds with incorporated vertical porosity and ceramic content gradients via a multimaterial extrusion 3DP system. Scaffolds of 0 wt% HA (PCL), 15 wt% HA (HA15), or 30 wt% HA (HA30) were fabricated with uniform composition and porosity (using 0.2 mm, 0.5 mm, or 0.9 mm on-center fiber spacing), uniform composition and gradient porosity, and…

A method to deliver patterned electrical impulses to Schwann cells cultured on an artificial axon

Neural Regeneration Research 2019 Volume 14, Issue 6, Pages 1052-1059

Information from the brain travels back and forth along peripheral nerves in the form of electrical impulses generated by neurons and these impulses have repetitive patterns. Schwann cells in peripheral nerves receive molecular signals from axons to coordinate the process of myelination. There is evidence, however, that non-molecular signals play an important role in myelination in the form of patterned electrical impulses generated by neuronal activity. The role of patterned electrical impulses has been investigated in the literature using co-cultures of neurons and myelinating cells. The co-culturing method, however, prevents the uncoupling of the direct effect of patterned electrical impulses…

Homogeneous hydroxyapatite/alginate composite hydrogel promotes calcified cartilage matrix deposition with potential for three-dimensional bioprinting

Biofabrication 2019 Volume 11, Issue 1, Article 015015

Calcified cartilage regeneration plays an important role in successful osteochondral repair, since it provides a biological and mechanical transition from the unmineralized cartilage at the articulating surface to the underlying mineralized bone. To biomimic native calcified cartilage in engineered constructs, here we test the hypothesis that hydroxyapatite (HAP) stimulates chondrocytes to secrete the characteristic matrix of calcified cartilage. Sodium citrate (SC) was added as a dispersant of HAP within alginate (ALG), and homogeneous dispersal of HAP within ALG hydrogel was confirmed using sedimentation tests, electron microscopy, and energy dispersive spectroscopy. To examine the biological performance of ALG/HAP composites, chondrocyte survival…

Multimaterial Segmented Fiber Printing for Gradient Tissue Engineering

Tissue Engineering Part C: Methods 2019

In this work, we present a printing method to fabricate scaffolds consisting of multimaterial segmented fibers. Particularly, we developed a reproducible printing process to create single fibers with multiple discrete compositions and control over the distribution of particulate ceramics—namely hydroxyapatite (HA) and β-tricalcium phosphate (TCP)—within poly(ɛ-caprolactone)-based composite scaffolds. Tensile testing revealed that the mechanical integrity of individual segmented fibers was preserved compared with nonsegmented fibers, and microcomputed tomography and thermal analysis confirmed the homogeneous distribution of ceramics incorporated in the fiber compositions. Moreover, we printed and characterized composite scaffolds containing model inverse radial gradients of HA and TCP that could…

Coating 3D Printed Polycaprolactone Scaffolds with Nanocellulose Promotes Growth and Differentiation of Mesenchymal Stem Cells

Biomacromolecules 2018 Voluem 19, Issue 11, Pages 4307-4319

3D printed polycaprolactone (PCL) has potential as a scaffold for bone tissue engineering, but the hydrophobic surface may hinder optimal cell responses. The surface properties can be improved by coating the scaffold with cellulose nanofibrils material (CNF), a multiscale hydrophilic biocompatible biomaterial derived from wood. In this study, human bone marrow-derived mesenchymal stem cells were cultured on tissue culture plates (TCP) and 3D printed PCL scaffolds coated with CNF. Cellular responses to the surfaces (viability, attachment, proliferation, and osteogenic differentiation) were documented. CNF significantly enhanced the hydrophilic properties of PCL scaffolds and promoted protein adsorption. Live/dead staining and lactate dehydrogenase…

Zein regulating apatite mineralization, degradability, in vitro cells responses and in vivo osteogenesis of 3D-printed scaffold of n-MS/ZN/PCL ternary composite

RSC Advances 2018 Volume 8, Pages 18745-18756

Bioactive and degradable scaffolds of nano magnesium silicate (n-MS)/zein (ZN)/poly(caprolactone) (PCL) ternary composites were prepared by 3D-printing method. The results showed that the 3D-printed scaffolds possessed controllable pore structure, and pore morphology, pore size, porosity and pore interconnectivity of the scaffolds can be efficiently adjusted. In addition, the apatite-mineralization ability of the scaffolds in simulated body fluids was obviously improved with the increase of ZN content, in which the scaffold with 20 w% ZN (C20) possessed excellent apatite-mineralization ability. Moreover, the degradability of the scaffolds was significantly enhanced with the increase of ZN content in the scaffolds. The degradation of…

Response of hPDLSCs on 3D printed PCL/PLGA composite scaffolds in vitro

Molecular Medicine Reports 2018 Volume 18 Issue 2, Pages 1335-1344

Three‑dimensional printed (3DP) scaffolds have become an excellent resource in alveolar bone regeneration. However, selecting suitable printable materials remains a challenge. In the present study, 3DP scaffolds were fabricated using three different ratios of poly (ε‑caprolactone) (PCL) and poly‑lactic‑co‑glycolic acid (PLGA), which were 0.1PCL/0.9PLGA, 0.5PCL/0.5PLGA and 0.9PCL/0.1PLGA. The surface characteristics and degradative properties of the scaffolds, and the response of human periodontal ligament stem cells (hPDLSCs) on the scaffolds, were assessed to examine the preferable ratio of PCL and PLGA for alveolar bone regeneration. The results demonstrated that the increased proportion of PLGA markedly accelerated the degradation, smoothed the surface…

3D printed mesoporous bioactive glass/metal-organic framework scaffolds with antitubercular drug delivery

Microporous and Mesoporous Materials 2018 Volume 272, Pages 24-30

Three-dimensional (3D) porous scaffolds with sustained drug delivery are pursued for osteoarticular tuberculosis therapy after surgery. In this study, mesoporous bioactive glass/metal-organic framework (MBG/MOF) scaffolds with sustained antitubercular drug release have been fabricated by 3D printing. The results showed that the MBG/MOF scaffolds possess macropores of ca. 400 μm and enhanced compressive strength of 3–7 MPa, also exhibited good biocompatibility and apatite forming ability in vitro. Furthermore, the drug release rate and pH microenvironment of the MBG/MOF scaffolds could be controlled due to the MOF degradation. These results indicated that the 3D printed MBG/MOF scaffolds are promising for treating osteoarticular tuberculosis.

3D Printed, PVA–PAA Hydrogel Loaded-Polycaprolactone Scaffold for the Delivery of Hydrophilic In-Situ Formed Sodium Indomethacin

Materials 2018 Voule 11, Issue 6, Article 1006

3D printed polycaprolactone (PCL)-blended scaffolds have been designed, prepared, and evaluated in vitro in this study prior to the incorporation of a polyvinyl alcohol–polyacrylic acid (PVA–PAA) hydrogel for the delivery of in situ-formed sodium indomethacin. The prepared PCL–PVA–PAA scaffold is proposed as a potential structural support system for load-bearing tissue damage where inflammation is prevalent. Uniaxial strain testing of the PCL-blended scaffolds were undertaken to determine the scaffold’s resistance to strain in addition to its thermal, structural, and porosimetric properties. The viscoelastic properties of the incorporated PVA–PAA hydrogel has also been determined, as well as the drug release profile of…

A novel surgical technique for a rat subcutaneous implantation of a tissue engineered scaffold

Acta Histochemica 2018 Volume 120, Issue 3, Pages 282-291

Objectives Subcutaneous implantations in small animal models are currently required for preclinical studies of acellular tissue to evaluate biocompatibility, including host recellularization and immunogenic reactivity. Methods Three rat subcutaneous implantation methods were evaluated in six Sprague Dawley rats. An acellular xenograft made from porcine pericardium was used as the tissue-scaffold. Three implantation methods were performed; 1) Suture method is where a tissue-scaffold was implanted by suturing its border to the external oblique muscle, 2) Control method is where a tissue-scaffold was implanted without any suturing or support, 3) Frame method is where a tissue-scaffold was attached to a circular frame…

3D printing of hybrid biomaterials for bone tissue engineering: Calcium-polyphosphate microparticles encapsulated by polycaprolactone

Acta Biomaterialia 2017 Volume 64, Pages 377-388

Here we describe the formulation of a morphogenetically active bio-ink consisting of amorphous microparticles (MP) prepared from Ca2+ and the physiological inorganic polymer, polyphosphate (polyP). Those MP had been fortified by mixing with poly-ε-caprolactone (PCL) to allow 3D-bioprinting. The resulting granular PCL/Ca-polyP-MP hybrid material, liquefied by short-time heating to 100 °C, was used for the 3D-printing of tissue-like scaffolds formed by strands with a thickness of 400 µm and a stacked architecture leaving ≈0.5 mm2-sized open holes enabling cell migration. The printed composite scaffold turned out to combine suitable biomechanical properties (Young’s modulus of 1.60 ± 0.1 GPa; Martens hardness of 153 ± 28 MPa), matching those of cortical…

Prevascularization of 3D printed bone scaffolds by bioactive hydrogels and cell co-culture

Journal of Biomedical Materials Research Part B: Applied Biomaterials 2017 Volume 106B, Pages 1788–1798

Vascularization is a fundamental prerequisite for large bone construct development and remains one of the main challenges of bone tissue engineering. Our current study presents the combination of 3D printing technique with a hydrogel-based prevascularization strategy to generate prevascularized bone constructs. Human adipose derived mesenchymal stem cells (ADMSC) and human umbilical vein endothelial cells (HUVEC) were encapsulated within our bioactive hydrogels, and the effects of culture conditions on in vitro vascularization were determined. We further generated composite constructs by forming 3D printed polycaprolactone/hydroxyapatite scaffolds coated with cell-laden hydrogels and determined how the co-culture affected vascularization and osteogenesis. It was demonstrated…

Biomimetic 3D printed scaffolds for meniscus tissue engineering

Bioprinting 2017 Volume 8, Pages 1-7

The menisci distribute loads to protect the articular cartilage of the knee joint from excessive stress. Injuries to their avascular inner regions do not heal, disrupt function, and increase the risk for knee osteoarthritis. Meniscus tissue engineering aims to restore normal meniscus function by use of regenerated tissue on bioengineered scaffolds. The primary purpose of this study was to design and 3D print polycaprolactone scaffolds that recapitulate the shape and structural components of the meniscus extracellular matrix to provide a template and structural support for complete cell-based meniscus regeneration. A secondary aim was to characterize 3D printed polycaprolactone scaffold fibre…

Molecularly imprinted polymers immobilized on 3D printed scaffolds as novel solid phase extraction sorbent for metergoline

Analytica Chimica Acta 2017 Volume 986, Pages 57-70

In the present work, a novel solid phase extraction (SPE) sorbent was developed based on molecularly imprinted polymers (MIPs) immobilized on 3D-printed scaffolds using polymer networks as MIP-immobilizing layer. MIPs were produced by precipitation polymerization in acetonitrile (ACN) using methacrylic acid (MAA) as functional monomer, trimethylolpropane trimethacrylate (TRIM) as crosslinker and metergoline as model template which allows final recognition of ergot alkaloid mycotoxins. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) analyses showed an average MIP particle size of 457 ± 145 nm. Functional MIP analysis revealed dissociation constants (KD) of 0.29 and 38.90 μM for high and low…

Evaluation of 3D-Printed Polycaprolactone Scaffolds Coated with Freeze-Dried Platelet-Rich Plasma for Bone Regeneration

Materials 2017 Volume 10, Issue 7, Article 831

Three-dimensional printing is one of the most promising techniques for the manufacturing of scaffolds for bone tissue engineering. However, a pure scaffold is limited by its biological properties. Platelet-rich plasma (PRP) has been shown to have the potential to improve the osteogenic effect. In this study, we improved the biological properties of scaffolds by coating 3D-printed polycaprolactone (PCL) scaffolds with freeze-dried and traditionally prepared PRP, and we evaluated these scaffolds through in vitro and in vivo experiments. In vitro, we evaluated the interaction between dental pulp stem cells (DPSCs) and the scaffolds by measuring cell proliferation, alkaline phosphatase (ALP) activity,…

Short-term hypoxic preconditioning promotes prevascularization in 3D bioprinted bone constructs with stromal vascular fraction derived cells

RSC Advances 2017 Volume 7, Pages 29312-29320

Reconstruction of complex, craniofacial bone defects often requires autogenous vascularized bone grafts, and still remains a challenge today. In order to address this issue, we isolated the stromal vascular fraction (SVF) from adipose tissues and maintained the phenotypes and the growth of endothelial lineage cells within SVF derived cells (SVFC) by incorporating an endothelial cell medium. We 3D bioprinted SVFC within our hydrogel bioinks and conditioned the constructs in either normoxia or hypoxia. We found that short-term hypoxic conditioning promoted vascularization-related gene expression, whereas long-term hypoxia impaired cell viability and vascularization. 3D bioprinted bone constructs composed of polycaprolactone/hydroxyapatite (PCL/HAp) and…

Fabrication and Evaluation of Electrospun, 3D-Bioplotted, and Combination of Electrospun/3D-Bioplotted Scaffolds for Tissue Engineering Applications

BioMed Research International 2017 Volume 2017, Article ID 6956794

Electrospun scaffolds provide a dense framework of nanofibers with pore sizes and fiber diameters that closely resemble the architecture of native extracellular matrix. However, it generates limited three-dimensional structures of relevant physiological thicknesses. 3D printing allows digitally controlled fabrication of three-dimensional single/multimaterial constructs with precisely ordered fiber and pore architecture in a single build. However, this approach generally lacks the ability to achieve submicron resolution features to mimic native tissue. The goal of this study was to fabricate and evaluate 3D printed, electrospun, and combination of 3D printed/electrospun scaffolds to mimic the native architecture of heterogeneous tissue. We assessed their…

Extraction and characterization of collagen from Antarctic and Sub-Antarctic squid and its potential application in hybrid scaffolds for tissue engineering

Materials Science and Engineering: C 2017 Volume 78, 1 September 2017, Pages 787–795

Collagen is the most abundant protein found in mammals and it exhibits a low immunogenicity, high biocompatibility and biodegradability when compared with others natural polymers. For this reason, it has been explored for the development of biologically instructive biomaterials with applications for tissue substitution and regeneration. Marine origin collagen has been pursued as an alternative to the more common bovine and porcine origins. This study focused on squid (Teuthoidea: Cephalopoda), particularly the Antarctic squid Kondakovia longimana and the Sub-Antarctic squid Illex argentinus as potential collagen sources. In this study, collagen has been isolated from the skins of the squids using…

Integrated 3D printed scaffolds and electrical stimulation for enhancing primary human cardiomyocyte cultures

Bioprinting 2017 Volume 6, Pages 18-24

3D printing technology is driving innovation in a wide variety of disciplines, and is beginning to make inroads into the fields of medicine and biology. In particular, 3D printing is being increasingly utilized for the design and fabrication of three-dimensional cell culture scaffolds. This technology allows for scaffolds to be produced rapidly while maintaining a great deal of control over the matrix architecture. This paper presents an effective technique for rapidly designing and fabricating scaffolds from silicone rubber and polycaprolactone (PCL), appropriate for primary human cardiomyocyte cell cultures. Additionally, a stimulation device is developed and presented which can provide 6…

Polycaprolactone-and polycaprolactone/ceramic-based 3D-bioplotted porous scaffolds for bone regeneration: A comparative study

Materials Science and Engineering: C 2017 Volume 79, Issue 1, Pages 326–335

One of the critical challenges that scaffolding faces in the organ and tissue regeneration field lies in mimicking the structure, and the chemical and biological properties of natural tissue. A high-level control over the architecture, mechanical properties and composition of the materials in contact with cells is essential to overcome such challenge. Therefore, definition of the method, materials and parameters for the production of scaffolds during the fabrication stage is critical. With the recent emergence of rapid prototyping (RP), it is now possible to create three-dimensional (3D) scaffolds with the essential characteristics for the proliferation and regeneration of tissues, such…

Effects of 3D-bioplotted polycaprolactone scaffold geometry on human adipose-derived stem cells viability and proliferation

Rapid Prototyping Journal 2017 Volume 23, Issue 3, Pages 534-542

Purpose This study investigates the effect of 3D-bioplotted polycaprolactone (PCL) scaffold geometry on the biological and mechanical characteristics of human adipose-derived stem cell (hASC) seeded constructs. Design/methodology/approach Four 3D-bioplotted scaffold disc designs (Ø14.5 x 2 mm) with two levels of strand-pore feature sizes and two strand laydown patterns (0°/90° or 0°/120°/240°) were evaluated for hASC viability, proliferation, and construct compressive stiffness after 14 days of in vitro cell culture. Findings Scaffolds with the highest porosity (smaller strand-pore size in 0°/120°/240°) yielded the highest hASC proliferation and viability. Further testing of this design in a 6 mm thick configuration showed that…

3D segmentation of intervertebral discs: from concept to the fabrication of patient-specific scaffolds

Journal of 3D Printing in Medicine 2017 Volume 1, Issue 2, Pages 91-101

Aim: To develop a methodology for producing patient-specific scaffolds that mimic the annulus fibrosus (AF) of the human intervertebral disc by means of combining MRI and 3D bioprinting. Methods: In order to obtain the AF 3D model from patient’s volumetric MRI dataset, the RheumaSCORE segmentation software was used. Polycaprolactone scaffolds with three different internal architectures were fabricated by 3D bioprinting, and characterized by microcomputed tomography. Results: The demonstrated methodology of a geometry reconstruction pipeline enabled us to successfully obtain an accurate AF model and 3D print patient-specific scaffolds with different internal architectures. Conclusion: The results guide us toward patient-specific intervertebral…

Three dimensional printing of calcium sulfate and mesoporous bioactive glass scaffolds for improving bone regeneration in vitro and in vivo

Scientific Reports 2017 Volume 7, Article number: 42556

In the clinic, bone defects resulting from infections, trauma, surgical resection and genetic malformations remain a significant challenge. In the field of bone tissue engineering, three-dimensional (3D) scaffolds are promising for the treatment of bone defects. In this study, calcium sulfate hydrate (CSH)/mesoporous bioactive glass (MBG) scaffolds were successfully fabricated using a 3D printing technique, which had a regular and uniform square macroporous structure, high porosity and excellent apatite mineralization ability. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured on scaffolds to evaluate hBMSC attachment, proliferation and osteogenesis-related gene expression. Critical-sized rat calvarial defects were applied to investigate the…

Remote Determination of Time-Dependent Stiffness of Surface-Degrading-Polymer Scaffolds Via Synchrotron-Based Imaging

Journal of Biomechanical Engineering 2017 Volume 139, Issue 4, Article 041004

Surface-degrading polymers have been widely used to fabricate scaffolds with the mechanical properties appropriate for tissue regeneration/repair. During their surface degradation, the material properties of polymers remain approximately unchanged, but the scaffold geometry and thus mechanical properties vary with time. This paper presents a novel method to determine the time-dependent mechanical properties, particularly stiffness, of scaffolds from the geometric changes captured by synchrotron-based imaging, with the help of finite element analysis (FEA). Three-dimensional (3D) tissue scaffolds were fabricated from surface-degrading polymers, and during their degradation, the tissue scaffolds were imaged via the synchrotron-based imaging to characterize their changing geometry. On…

PCL Imaging

Traditional invasive and synchrotron-based non-invasive assessments of 3D-printed hybrid cartilage constructs

Tissue Engineering Part C: Methods 2017 Volume 23, Issue 3, Pages 156-168

Three-dimensional (3D)-printed constructs made of polycaprolactone (PCL) and chondrocyte-impregnated alginate hydrogel (hybrid cartilage constructs) mimic the biphasic nature of articular cartilage, offering promise for cartilage tissue engineering (CTE) applications. However, the regulatory pathway for medical device development requires validation of such constructs through in vitro bench tests and in vivo preclinical examinations premarket approval. Furthermore, non-invasive imaging techniques are required for effective evaluation of the progress of these cartilage constructs, especially when implanted in animal models or human subjects. However, characterization of the individual components of the hybrid cartilage constructs and their associated time-dependent structural changes by currently available non-invasive…

Pyrintegrin Induces Soft Tissue Formation by Transplanted or Endogenous Cells

Scientific Reports 2017 Issue 7, Article number: 36402

Focal adipose deficiency, such as lipoatrophy, lumpectomy or facial trauma, is a formidable challenge in reconstructive medicine, and yet scarcely investigated in experimental studies. Here, we report that Pyrintegrin (Ptn), a 2,4-disubstituted pyrimidine known to promote embryonic stem cells survival, is robustly adipogenic and induces postnatal adipose tissue formation in vivo of transplanted adipose stem/progenitor cells (ASCs) and recruited endogenous cells. In vitro, Ptn stimulated human adipose tissue derived ASCs to differentiate into lipid-laden adipocytes by upregulating peroxisome proliferator-activated receptor (PPARγ) and CCAAT/enhancer-binding protein-α (C/EBPα), with differentiated cells increasingly secreting adiponectin, leptin, glycerol and total triglycerides. Ptn-primed human ASCs seeded…

3D printing of pearl/CaSO4 composite scaffolds for bone regeneration

Journal of Materials Chemistry B 2017 Volume 6, Issue 3, Pages 499-509

The development of biomaterials with high osteogenic ability for fast osteointegration with a host bone is of great interest. In this study, pearl/CaSO4 composite scaffolds were fabricated using three-dimensional (3D) printing, followed by a hydration process. The pearl/CaSO4 scaffolds showed uniform interconnected macropores (∼400 μm), high porosity (∼60%), and enhanced compressive strength. With CaSO4 scaffolds as a control, the biological properties of the pearl/CaSO4 scaffolds were evaluated in vitro and in vivo. The results showed that the pearl/CaSO4 scaffolds possessed a good apatite-forming ability and stimulated the proliferation and differentiation of rat bone mesenchymal stem cells (rBMSCs), as well as…

Low-dose phase-based X-ray imaging techniques for in situ soft tissue engineering assessments

Biomaterials 2016 Volume 82, Pages 151–167

In tissue engineering, non-invasive imaging of biomaterial scaffolds and tissues in living systems is essential to longitudinal animal studies for assessments without interrupting the repair process. Conventional X-ray imaging is inadequate for use in soft tissue engineering due to the limited absorption difference between the soft tissue and biomaterial scaffolds. X-ray phase-based imaging techniques that derive contrast from refraction or phase effects rather than absorption can provide the necessary contrast to see low-density biomaterial scaffolds and tissues in large living systems. This paper explores and compares three synchrotron phase-based X-ray imaging techniques—computed tomography (CT)-diffraction enhanced imaging (DEI), -analyzer based imaging…

Three-dimensional printing of cerium-incorporated mesoporous calcium-silicate scaffolds for bone repair

Journal of Materials Science 2016 Volume 51, Issue 2, Pages 836-844

In the study, we developed hierarchical composite scaffolds by 3D printing technique with mesoporous CaSiO3 containing controlled amounts of Ce substitution in Ca–Si system. The scaffolds were porous with 3D interconnected large pores (size ~400 μm) and an overall porosity above 70 %, combined with a relative high compressive strength (~7 MPa). These properties are essential for enhancing bone ingrowth in tissue engineering. The in vitro biological properties of apatite formation, cell proliferation, and differentiation were characterized on CeO2-MCS scaffolds and MCS scaffolds. Results indicated that CeO2-MCS scaffolds induced similar apatite deposition and cell attachment of human bone marrow stromal…

Hyperelastic “bone”: A highly versatile, growth factor–free, osteoregenerative, scalable, and surgically friendly biomaterial

Science Translational Medicine 2016 Volume 8, Issue 358, Pages 358ra127

Despite substantial attention given to the development of osteoregenerative biomaterials, severe deficiencies remain in current products. These limitations include an inability to adequately, rapidly, and reproducibly regenerate new bone; high costs and limited manufacturing capacity; and lack of surgical ease of handling. To address these shortcomings, we generated a new, synthetic osteoregenerative biomaterial, hyperelastic “bone” (HB). HB, which is composed of 90 weight % (wt %) hydroxyapatite and 10 wt % polycaprolactone or poly(lactic-co-glycolic acid), could be rapidly three-dimensionally (3D) printed (up to 275 cm3/hour) from room temperature extruded liquid inks. The resulting 3D-printed HB exhibited elastic mechanical properties (~32…

Synchrotron-Based in Situ Characterization of the Scaffold Mass Loss from Erosion Degradation

Journal of Functional Biomaterials 2016 Volume 7, Issue 3, 17

The mass loss behavior of degradable tissue scaffolds is critical to their lifespan and other degradation-related properties including mechanical strength and mass transport characteristics. This paper presents a novel method based on synchrotron imaging to characterize the scaffold mass loss from erosion degradation in situ, or without the need of extracting scaffolds once implanted. Specifically, the surface-eroding degradation of scaffolds in a degrading medium was monitored in situ by synchrotron-based imaging; and the time-dependent geometry of scaffolds captured by images was then employed to estimate their mass loss with time, based on the mathematical model that was adopted from the…

PCL Imaging

Building the basis for patient-specific meniscal scaffolds: From human knee MRI to fabrication of 3D printed scaffolds

Bioprinting 2016 Volumes 1–2, Pages 1–10

The current strategies for the transplantation of meniscus should be strengthened to tackle the faced limitations of current methods in the clinics. One of the limitations is that current implants are not patient-specific. There is, therefore, a pressing need in the clinics to develop patient-specific implants. The aim of this study was to demonstrate a semi-automatic way of segmenting meniscus tissues from patients’ volumetric knee magnetic resonance imaging (MRI) datasets in order to obtain patient-specific 3D models for 3D printing of patient-specific constructs. High-quality MRI volumetric images were acquired from five healthy male human subjects. The advanced segmentation software, RheumaSCORE,…

In vitro characterization of design and compressive properties of 3D-biofabricated/decellularized hybrid grafts for tracheal tissue engineering

Journal of the Mechanical Behavior of Biomedical Materials 2016 Volume 59, Pages 572–585

Infection or damage to the trachea, a thin walled and cartilage reinforced conduit that connects the pharynx and larynx to the lungs, leads to serious respiratory medical conditions which can often prove fatal. Current clinical strategies for complex tracheal reconstruction are of limited availability and efficacy, but tissue engineering and regenerative medicine approaches may provide viable alternatives. In this study, we have developed a new “hybrid graft” approach that utilizes decellularized tracheal tissue along with a resorbable polymer scaffold, and holds promise for potential clinical applications. First, we evaluated the effect of our decellularization process on the compression properties of…

Using synchrotron radiation inline phase-contrast imaging computed tomography to visualize three-dimensional printed hybrid constructs for cartilage tissue engineering

Journal of Synchrotron Radiation 2016 Volume 23, Issue 3, Pages 802-812

Synchrotron radiation inline phase-contrast imaging combined with computed tomography (SR-inline-PCI-CT) offers great potential for non-invasive characterization and three-dimensional visualization of fine features in weakly absorbing materials and tissues. For cartilage tissue engineering, the biomaterials and any associated cartilage extracellular matrix (ECM) that is secreted over time are difficult to image using conventional absorption-based imaging techniques. For example, three-dimensional printed polycaprolactone (PCL)/alginate/cell hybrid constructs have low, but different, refractive indices and thicknesses. This paper presents a study on the optimization and utilization of inline-PCI-CT for visualizing the components of three-dimensional printed PCL/alginate/cell hybrid constructs for cartilage tissue engineering. First, histological analysis…

The effect of calcium sulfate incorporation on physiochemical and biological properties of 3D-printed mesoporous calcium silicate cement scaffolds

Microporous and Mesoporous Materials 2016 Volume 241, Issue 15, Pages 11–20

Development of 3D porous scaffolds with proper mechanical strength is crucial in bone tissue engineering. In this study, calcium sulfate hemihydrate (CSH) cement was functionally incorporated into mesoporous calcium silicate (MCS) through a 3D printing technique in order to improve the scaffold strength. Compared to printed MCS scaffolds, the characterizations revealed that 20% CSH incorporation had enhanced their compressive strength by 2 times via 4 weeks’ hydration. Furthermore, CSH incorporation prevented the fast pH value rise and achieved a balanced degradation rate. SEM observations showed a good apatite formation on the surfaces of both MCS and MCS/CSH scaffolds. Cellular experiments…

Three-dimensional printing of tricalcium silicate/mesoporous bioactive glass cement scaffolds for bone regeneration

Journal of Materials Chemistry B 2016 Volume 4, Pages 7452-7463

Bone defects, particularly large bone defects resulting from infections, trauma, surgical resection or genetic malformations, maintain a significant challenge for clinicians. In this study, the tricalcium silicate/mesoporous bioactive glass (C3S/MBG) cement scaffolds were successfully fabricated for the first time by 3D printing with a curing process, which combined the hydraulicity of C3S with the excellent biological property of MBG together. The C3S/MBG scaffolds exhibited 3D interconnected macropores (~400μm), high porosity (~70%), enhanced mechanical strength (>12MPa) and excellent apatite mineralization ability. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured on the scaffolds to evaluate their cell responses, and the results…

In vitro colonization of stratified bioactive scaffolds by pre-osteoblast cells

Acta Biomaterialia 2016 Volume 44, Issue 15, Pages 73–84

Mesoporous bioactive glass-polycaprolactone (MBG-PCL) scaffolds have been prepared by robocasting, a layer by layer rapid prototyping method, by stacking of individual strati. Each stratus was independently analyzed during the cell culture tests with MC3T3-E1 preosteblast-like cells. The presence of MBG stimulates the colonization of the scaffolds by increasing the cell proliferation and differentiation. MBG-PCL composites not only enhanced pre-osteoblast functions but also allowed cell movement along its surface, reaching the upper stratus faster than in pure PCL scaffolds. The cells behavior on each individual stratus revealed that the scaffolds colonization depends on the chemical stimuli supplied by the MBG dissolution…

Periodontal ligament stem/progenitor cells with protein-releasing scaffolds for cementum formation and integration on dentin surface

Connective Tissue Research 2016 Volume 57, Issue 6, Pages 488-495

Purpose/Aim: Cementogenesis is a critical step in periodontal tissue regeneration given the essential role of cementum in anchoring teeth to the alveolar bone. This study is designed to achieve integrated cementum formation on the root surfaces of human teeth using growth factor–releasing scaffolds with periodontal ligament stem/progenitor cells (PDLSCs). Materials and methods: Human PDLSCs were sorted by CD146 expression, and characterized using CFU-F assay and induced multi-lineage differentiation. Polycaprolactone scaffolds were fabricated using 3D printing, embedded with poly(lactic-co-glycolic acids) (PLGA) microspheres encapsulating connective tissue growth factor (CTGF), bone morphogenetic protein-2 (BMP-2), or bone morphogenetic protein-7 (BMP-7). After removing cementum on…

Micro-precise spatiotemporal delivery system embedded in 3D printing for complex tissue regeneration

Biofabrication 2016 Volume 8, Number 2, 025003

Three dimensional (3D) printing has emerged as an efficient tool for tissue engineering and regenerative medicine, given its advantages for constructing custom-designed scaffolds with tunable microstructure/physical properties. Here we developed a micro-precise spatiotemporal delivery system embedded in 3D printed scaffolds. PLGA microspheres (μS) were encapsulated with growth factors (GFs) and then embedded inside PCL microfibers that constitute custom-designed 3D scaffolds. Given the substantial difference in the melting points between PLGA and PCL and their low heat conductivity, μS were able to maintain its original structure while protecting GF’s bioactivities. Micro-precise spatial control of multiple GFs was achieved by interchanging dispensing…

Analyzing biological performance of 3D-printed, cell-impregnated hybrid constructs for cartilage tissue engineering

Tissue Engineering Part C: Methods 2016 Volume 22, Issue 3, Pages 173-188

Three-dimensional (3D) bioprinting of hybrid constructs is a promising biofabrication method for cartilage tissue engineering because a synthetic polymer framework and cell-impregnated hydrogel provide structural and biological features of cartilage, respectively. During bioprinting, impregnated cells may be subjected to high temperatures (caused by the adjacent melted polymer) and process-induced mechanical forces, potentially compromising cell function. This study addresses these biofabrication issues, evaluating the heat distribution of printed polycaprolactone (PCL) strands and the rheological property and structural stability of alginate hydrogels at various temperatures and concentrations. The biocompatibility of parameters from these studies was tested by culturing 3D hybrid constructs bioprinted…

3D fibre deposition and stereolithography techniques for the design of multifunctional nanocomposite magnetic scaffolds

Journal of Materials Science: Materials in Medicine 2015 Volume 26, Issue 250, Pages 250ff

Magnetic nanocomposite scaffolds based on poly(ε-caprolactone) and poly(ethylene glycol) were fabricated by 3D fibre deposition modelling (FDM) and stereolithography techniques. In addition, hybrid coaxial and bilayer magnetic scaffolds were produced by combining such techniques. The aim of the current research was to analyse some structural and functional features of 3D magnetic scaffolds obtained by the 3D fibre deposition technique and by stereolithography as well as features of multimaterial scaffolds in the form of coaxial and bilayer structures obtained by the proper integration of such methods. The compressive mechanical behaviour of these scaffolds was investigated in a wet environment at 37…

Characterization of Material–Process–Structure Interactions in the 3D Bioplotting of Polycaprolactone

3D Printing and Additive Manufacturing 2015 Volume 2, Issue 1, Pages 20-31

Three-dimensional (3D) bioplotting is a melt-extrusion-based additive manufacturing process used to fabricate 3D scaffolds for tissue engineering applications. This study investigates the relationship between material rheology, process parameters, and scaffold characteristics during 3D bioplotting of polycaprolactone (PCL). The effects of two process parameters, extrusion temperature and nozzle diameter, on resultant scaffold structure and compression strength were studied using design of experiments. PCL scaffolds designed for a 24-well culture plate (Ø 14 mm × 2 mm) were bioplotted in a 0°/90° laydown pattern at three levels of extrusion temperature (80°C, 90°C, and 100°C) and two levels of nozzle inner diameter (0.3 and 0.4 mm) at…

PCL

Glasses in bone regeneration: A multiscale issue

Journal of Non-Crystalline Solids 2015 Volume 432, Part A, Pages 9–14

3D scaffolds based in mesoporous bioactive glasses (MBGs) are being widely investigated to use in bone tissue engineering (TE) applications. These scaffolds are often obtained by rapid prototyping (RP) and exhibit an array of interconnected pores in a hierarchy of sizes. The ordered mesopore network (around 4 nm in diameter) is optimal for the adsorption and release of bone inductor biomolecules, and the arrangement of macropores over 100 μm facilitates the bone cell ingrowths and angiogenesis. Nevertheless MBG composition can be varied almost infinitely at the atomic scale by including in the glass network oxides of inorganic elements with a…

A bio-friendly, green route to processable, biocompatible graphene/polymer composites

RSC Advances 2015 Volume 5, Issue 56, 45284-45290

Graphene-based polymer composites are a very promising class of compounds for tissue engineering scaffolds. However, in general the methods of synthesis are environmentally hazardous and residual toxic materials can affect the biocompatibility significantly. In this paper a simple, scalable, environmentally-friendly, microwave-assisted synthesis is described that results in conducting graphene/polycaprolactone composites that retain the processability and biocompatibility of the pristine polymer without introducing possibly hazardous reducing agents. Composites of polycaprolactone and graphene oxide were synthesised in a single step by the ring-opening polymerisation of ε-caprolactone in the presence of dispersed graphene oxide nanosheets under microwave irradiation. The graphene oxide provides a…

The Application of Three-Dimensional Printing in Animal Model of Augmentation Rhinoplasty

Annals of Biomedical Engineering 2015 Volume 43, Issue 9, Pages 2153-2162

The role of three-dimensional (3D) printing has expanded in diverse areas in medicine. As plastic surgery needs to fulfill the different demands from diverse individuals, the applications of tailored 3D printing will become indispensable. In this study, we evaluated the feasibility of using 3D-printed polycaprolactone (PCL) scaffold seeded with fibrin/chondrocytes as a new dorsal augmentation material for rhinoplasty. The construct was surgically implanted on the nasal dorsum in the subperiosteal plane of six rabbits. The implants were harvested 4 and 12 weeks after implantation and evaluated by gross morphological assessment, radiographic imaging, and histologic examination. The initial shape of the…

Alginate Microspheroid Encapsulation and Delivery of MG-63 Cells Into Polycaprolactone Scaffolds: A New Biofabrication Approach for Tissue Engineering Constructs

Journal of Nanotechnology in Engineering and Medicine 2015 Volume 6, Issue 2, 021003

Scaffolds play an important role in tissue engineering by providing structural framework and a surface for cells to attach, proliferate, and secrete extracellular matrix (ECM). In order to enable efficient tissue formation, delivering sufficient cells into the scaffold three-dimensional (3D) matrix using traditional static and dynamic seeding methods continues to be a critical challenge. In this study, we investigate a new cell delivery approach utilizing deposition of hydrogel-cell encapsulated microspheroids into polycaprolactone (PCL) scaffolds to improve the seeding efficiency. Three-dimensional-bioplotted PCL constructs (0 deg/90 deg lay down, 284 ± 6 μm strand width, and 555 ± 8 μm strand separation) inoculated with MG-63 model bone cells encapsulated within…

Hyperthermia Induced in Magnetic Scaffolds for Bone Tissue Engineering

IEEE Transactions on Magnetics 2014 Volume 50, Issue 11, Pages 1-7

The design and fabrication of advanced biocompatible and bioresorbable materials able to mimic the natural tissues present in the human body constitutes an important challenge in regenerative medicine. The size-dependent properties that materials exhibit at the nanoscale as a consequence of their higher surface-to-volume ratio have opened a wide range of opportunities for applications in almost every imaginable field. In this regard, the incorporation of magnetic nanoparticles (MNPs) into biocompatible scaffold formulations provides final materials with additional multifunctionality and reinforced mechanical properties for bone tissue engineering applications. In addition to the biological implications due to their magnetic character (i.e., magnetic…

Computed Tomography Diffraction-Enhanced Imaging for In Situ Visualization of Tissue Scaffolds Implanted in Cartilage

Tissue Engineering Part C: Methods 2014 Volume 20, Issue 2, Pages 140-148

Long-term in vivo studies on animal models and advances from animal to human studies should rely on noninvasive monitoring methods. Synchrotron radiation (SR)-diffraction enhanced imaging (DEI) has shown great promise as a noninvasive method for visualizing native and/or engineered tissues and bio-microstructures with appreciable details in situ. The objective of this study was to investigate SR-DEI for in situ visualization and characterization of tissue-engineered scaffolds implanted in cartilage. A piglet stifle joint implanted with an engineered scaffold made from poly-ɛ-caprolactone was imaged using SR computed tomography (CT)-DEI at an X-ray energy of 40 keV. For comparison, in situ visualization was also…

3D-Printed Magnetic Fe3O4/MBG/PCL Composite Scaffolds with Multifunctionality of Bone Regeneration, Local Anticancer Drug Delivery and Hyperthermia

Journal of Materials Chemistry B 2014 Volume 2, Issue 43, Pages 7583-7595

In this study, three-dimensional (3D) magnetic Fe3O4 nanoparticles containing mesoporous bioactive glass/polycaprolactone (Fe3O4/MBG/PCL) composite scaffolds have been fabricated by the 3D-printing technique. The physiochemical properties, in vitro bioactivity, anticancer drug delivery, mechanical strength, magnetic heating ability and cell response of Fe3O4/MBG/PCL scaffolds were systematically investigated. The results showed that Fe3O4/MBG/PCL scaffolds had uniform macropores of 400 μm, high porosity of 60% and excellent compressive strength of 13–16 MPa. The incorporation of magnetic Fe3O4 nanoparticles into MBG/PCL scaffolds did not influence their apatite mineralization ability but endowed excellent magnetic heating ability and significantly stimulated proliferation, alkaline phosphatase (ALP) activity, osteogenesis-related gene…

Protein-releasing polymeric scaffolds induce fibrochondrocytic differentiation of endogenous cells for knee meniscus regeneration in sheep

Science Translational Medicine 2014 Volume 6, Issue 266, Pages 266ra171

Regeneration of complex tissues, such as kidney, liver, and cartilage, continues to be a scientific and translational challenge. Survival of ex vivo cultured, transplanted cells in tissue grafts is among one of the key barriers. Meniscus is a complex tissue consisting of collagen fibers and proteoglycans with gradient phenotypes of fibrocartilage and functions to provide congruence of the knee joint, without which the patient is likely to develop arthritis. Endogenous stem/progenitor cells regenerated the knee meniscus upon spatially released human connective tissue growth factor (CTGF) and transforming growth factor–β3 (TGFβ3) from a three-dimensional (3D)–printed biomaterial, enabling functional knee recovery. Sequentially…

Tissue‐Engineered Tracheal Reconstruction Using Three‐Dimensionally Printed Artificial Tracheal Graft: Preliminary Report

Artificial Organs 2014 Volume 38, Issue 6, pages E95–E105

Three-dimensional printing has come into the spotlight in the realm of tissue engineering. We intended to evaluate the plausibility of 3D-printed (3DP) scaffold coated with mesenchymal stem cells (MSCs) seeded in fibrin for the repair of partial tracheal defects. MSCs from rabbit bone marrow were expanded and cultured. A half-pipe-shaped 3DP polycaprolactone scaffold was coated with the MSCs seeded in fibrin. The half-pipe tracheal graft was implanted on a 10 × 10-mm artificial tracheal defect in four rabbits. Four and eight weeks after the operation, the reconstructed sites were evaluated bronchoscopically, radiologically, histologically, and functionally. None of the four rabbits showed any…

Three-Dimensional Printed Multiphase Scaffolds for Regeneration of Periodontium Complex

Tissue Engineering Part A 2014 Volume 20, Issue 7-8, Pages 1342-1351

Tooth-supporting periodontium forms a complex with multiple tissues, including cementum, periodontal ligament (PDL), and alveolar bone. In this study, we developed multiphase region-specific microscaffolds with spatiotemporal delivery of bioactive cues for integrated periodontium regeneration. Polycarprolactione-hydroxylapatite (90:10 wt%) scaffolds were fabricated using three-dimensional printing seamlessly in three phases: 100-μm microchannels in Phase A designed for cementum/dentin interface, 600-μm microchannels in Phase B designed for the PDL, and 300-μm microchannels in Phase C designed for alveolar bone. Recombinant human amelogenin, connective tissue growth factor, and bone morphogenetic protein-2 were spatially delivered and time-released in Phases A, B, and C, respectively. Upon 4-week in…

Advanced composites for hard-tissue engineering based on PCL/organic–inorganic hybrid fillers: From the design of 2D substrates to 3D rapid prototyped scaffolds

Polymer Composites 2013 Volume 34, Issue 9, Pages 1413–1417

The bioactivity of sol–gel synthesized poly(ε-caprolactone) (PCL)/TiO2 or poly(ε-caprolactone)/ZrO2 particles was already known. In designing innovative 2D composite substrates for hard-tissue engineering, the possibility to embed PCL/TiO2 or PCL/ZrO2 hybrid fillers into a PCL matrix was previously proposed. In the present study, the potential of 3D fiber-deposition technique to design morphologically controlled scaffolds consisting of PCL reinforced with PCL/TiO2 or PCL/ZrO2 hybrid fillers was demonstrated. Finite element analysis was initially carried out on 2D substrates to find a correlation between the previously obtained results from the small punch test and the Young’s modulus of the materials, whilst mechanical and biological…

Physiologic load-bearing characteristics of autografts, allografts, and polymer-based scaffolds in a critical sized segmental defect of long bone: an experimental study

International Journal of Nanomedicine 2013 Volume 8, Pages 1637-1643

Background To address the challenge of treating critical sized intercalary defects, we hypothesized that under physiologic cyclic loading, autografts, allografts, and scaffolds loaded with and without human mesenchymal stem cells (hMSCs) would have different biomechanical characteristics. Methods Using a rat femoral defect model, 46 rats were assigned to four groups, ie, autograft (n = 12), allograft (n = 10), scaffold (n = 13), and scaffold with hMSCs (n = 11). The scaffold groups used a 5 mm segment of scaffold composed of 80% poly-ε-caprolactone and 20% hydroxyapatite. Rats were sacrificed 4 months postoperatively, and the repairs were assessed radiographically and…

Systematic analysis of injectable materials and 3D rapid prototyped magnetic scaffolds: from CNS applications to soft and hard tissue repair/regeneration

Procedia Engineering 2013 Volume 59, Pages 233–239

Over the past years, polymer-based materials have attracted research interest in the field of tissue repair and regeneration. As reported in literature, different injectable systems have been proposed, trying to reduce surgical invasiveness. In a first step of the current research, the rheological and functional features of injecatble hydrogel-based materials for central nervous system applications or soft tissue regeneration (collagen/PEG semi-IPNs) as well as for hard tissue engineering (alginate/iron-doped hydroxyapatite) were evaluated. Then, the study was also devoted to the development of 3D nanocomposite poly(ɛ- caprolactone)/iron-doped hydroxyapatite scaffolds for bone tissue engineering, providing a preliminary approach to assess magnetic attraction…

Layered Gradient Nonwovens of In Situ Crosslinked Electrospun Collagenous Nanofibers Used as Modular Scaffold Systems for Soft Tissue Regeneration

Advanced Functional Materials 2013 Volume 23, Issue 26, Pages 3277-3285

In a versatile modular scaffold system, gradient nonwovens of in situ crosslinked gelatin nanofibers (CGN), fabricated by reactive electrospinning, are laminated with perforated layers and nonwovens of thermoplastic non-crosslinked biodegradable polyesters. The addition of glyoxal to a gelatin solution in a non-toxic solvent mixture consisting of acetic acid, ethyl acetate, and water (5:3:2 w/w/w) enables the in situ crosslinking of gelatin nanofibers during electrospinning. The use of this fluorine-free crosslinking system eliminates the need of post-treatment crosslinking and purification steps typical for conventional CGN scaffolds. The slowly progressing crosslinking of the dissolved gelatin in the presence of glyoxal increases the…

Hierarchical Fibrillar Scaffolds Obtained by Non-conventional Layer-By-Layer Electrostatic Self-Assembly

Advanced Healthcare Materials 2013 Volume 2, Issue 3, pages 422–427

A new application of layer-by-layer assembly is presented, able to create nano/micro fibrils or nanocoatings inside 3D scaffolds using non-fibrillar polyelectrolytes for tissue-engineering applications. This approach shows promise for developing advanced scaffolds with controlled nano/micro environments, and nature and architectures similar to the natural extracellular matrix, leading to improved biological performance.

Design and preparation of biocompatible zwitterionic hydroxyapatite

Journal of Materials Chemistry B 2013 Volume 11, Issue 1, Pages 1595-1606

This study reports the design and preparation of zwitterionic nanocrystalline hydroxyapatite (HA) capable of inhibiting bacterial adhesion while allowing osteoblast cell colonization. The surface functionalization of HA powders was carried out by post-synthesis grafting of 3-aminopropyltriethoxysilane (APTES) and carboxyethylsilanetriol sodium salt (CES) as amine and carboxylate precursors, respectively. The successful functionalization of HA surfaces was assessed by elemental chemical analysis, FTIR, 29Si, 31P and 13C solid state CP/MAS NMR and ζ-potential measurements, and the zwitterionic nature of the synthesized HA was proved through the presence of –NH3+/–COO− pairs on the material surfaces. With the aim of evaluating the feasibility of…

Mesoporous bioactive scaffolds prepared with cerium-, gallium- and zinc-containing glasses

Acta Biomaterialia 2013 Volume 9, Issue 1, Pages 4836–4844

Mesoporous bioactive glass scaffolds (MBG_Scs), based on 80% SiO2–15% CaO–5% P2O5 (in mol.%) mesoporous sol–gel glasses substituted with Ce2O3, Ga2O3 (both 0.2% or 1.0%) and ZnO (0.4% or 2.0%), were synthesized by combination of evaporation-induced self-assembly and rapid prototyping techniques. Cerium, gallium and zinc trace elements were selected because of their inherent beneficial biological properties. Fabricated scaffolds were characterized and compared with unsubstituted scaffold (B_Sc). All of them contained well interconnected ultralarge pores (pores >400 μm) ideal for vascular ingrowth and proliferation of cells. Macropores of size 100–400 μm were present inside the scaffolds. In addition, low-angle X-ray diffraction showed…

An in vivo study on the effect of scaffold geometry and growth factor release on the healing of bone defects

Journal of Tissue Engineering and Regenerative Medicine 2013 Volume 7, Issue 9, Pages 687–696

The hypothesis of this study was that the extent of bone regeneration could be enhanced by using scaffolds with appropriate geometry, and that such an effect could be further increased by mimicking the natural timing of appearance of bone morphogenetic proteins BMP-2 and BMP-7 after fracture. Bioplotted poly(ε-caprolactone) (PCL) disks with four different fibre organizations were used to study the effect of 3D scaffold architecture on the healing of bone defects in a rat pelvis model. Moreover, one PCL construct was further modified by introducing a nanoparticulate sequential BMP-2/BMP-7 delivery system into this scaffold. Scaffolds and functionalized construct along with…

In‐vivo behavior of Si‐hydroxyapatite/polycaprolactone/DMB scaffolds fabricated by 3D printing

Journal of Biomedical Materials Research Part A 2013 Volume 101A, Issue 7, Pages 2038–2048

Scaffolds made of polycaprolactone and nanocrystalline silicon-substituted hydroxyapatite have been fabricated by 3D printing rapid prototyping technique. To asses that the scaffolds fulfill the requirements to be considered for bone grafting applications, they were implanted in New Zealand rabbits. Histological and radiological studies have demonstrated that the scaffolds implanted in bone exhibited an excellent osteointegration without the interposition of fibrous tissue between bone and implants and without immune response after 4 months of implantation. In addition, we have evaluated the possibility of improving the scaffolds efficiency by incorporating demineralized bone matrix during the preparation by 3D printing. When demineralized bone…

A biomimetic growth factor delivery strategy for enhanced regeneration of iliac crest defects

Biomedical Materials 2013 Volume 8, Number 4, 045009

The importance of provision of growth factors in the engineering of tissues has long been shown to control the behavior of the cells within the construct and several approaches were applied toward this end. In nature, more than one type of growth factor is known to be effective during the healing of tissue defects and their peak concentrations are not always simultaneous. One of the most recent strategies includes the delivery of a combination of growth factors with the dose and timing to mimic the natural regeneration cascade. The sequential delivery of bone morphogenetic proteins BMP-2 and BMP-7 which are…

Three-Dimensional Poly(ε-caprolactone) Bioactive Scaffolds with Controlled Structural and Surface Properties

Biomacromolecules 2012 Volume 13, Issue 11, Pages 3510-3521

The requirement of a multifunctional scaffold for tissue engineering capable to offer at the same time tunable structural properties and bioactive interface is still unpaired. Here we present three-dimensional (3D) biodegradable polymeric (PCL) scaffolds with controlled morphology, macro-, micro-, and nano-mechanical performances endowed with bioactive moieties (RGD peptides) at the surface. Such result was obtained by a combination of rapid prototyping (e.g., 3D fiber deposition) and surface treatment approach (aminolysis followed by peptide coupling). By properly designing process conditions, a control over the mechanical and biological performances of the structure was achieved with a capability to tune the value of…

A route toward the development of 3D magnetic scaffolds with tailored mechanical and morphological properties for hard tissue regeneration: Preliminary study

Virtual and Physical Prototyping 2011 Volume 6, Issue 4, Pages 189-195

A basic approach toward the design of three-dimensional (3D) rapid prototyped magnetic scaffolds for hard-tissue regeneration has been proposed. In particular, 3D scaffolds consisting of a poly(ε-caprolactone) (PCL) matrix and iron oxide (Fe3O4) or iron-doped hydroxyapatite (FeHA) nanoparticles were fabricated through a 3D fibre deposition technique. As a first approach, a polymer to nanoparticle weight ratio of 90/10 (wt/wt) was used. The effect of the inclusion of both kinds of nanoparticles on the mechanical, magnetic, and biological performances of the scaffolds was studied. The inclusion of Fe3O4 and FeHA nanoparticles generally improves the modulus and the yield stress of the…

A basic approach toward the development of nanocomposite magnetic scaffolds for advanced bone tissue engineering

Jounal of Applied Polymer Science 2011 Volume 122, Issue 6, Pages 3599-3605

Magnetic scaffolds for bone tissue engineering based on a poly(ε-caprolactone) (PCL) matrix and iron oxide (Fe3O4) magnetic nanoparticles were designed and developed through a three-dimensional (3D) fiber-deposition technique. PCL/Fe3O4 scaffolds were characterized by a 90/10 w/w composition. Tensile and magnetic measurements were carried out, and nondestructive 3D imaging was performed through microcomputed tomography (Micro-CT). Furthermore, confocal analysis was undertaken to investigate human mesenchymal stem cell adhesion and spreading on the PCL/Fe3O4 nanocomposite fibers. The results suggest that nanoparticles mechanically reinforced the PCL matrix; the elastic modulus and the maximum stress increased about 10 and 30%, respectively. However, the maximum strain…

Valproate release from polycaprolactone implants prepared by 3D-bioplotting

Die Pharmazie - An International Journal of Pharmaceutical Sciences 2011 Volume 66, Number 7, Pages 511-516

In this study we examined the release kinetics of valproate from polycaprolactone (PCL) implants constructed for local antiepileptic therapy. The PCL implants were produced with a novel 3D-Bioplotting technology. Release kinetics were determined by superfusion of these implants. Valproate was measured in the superfusate fractions with high pressure liquid chromatography (HPLC). The HPLC measurements were linear over a concentration range of 10-500 g/mL for valproate and the limit of quantification was found to be 9 g/mL. The HPLC method used is simple, accurate and sensitive. Within the first day, valproate (10%w/w)-PCL implants released already 77% of the maximum possible liberated…

Poly (caprolactone) based magnetic scaffolds for bone tissue engineering

Journal of Applied Physics 2011 Volume 109, Issue 7, 07B313

Synthetic scaffolds for tissue engineering coupled to stem cells represent a promising approach aiming to promote the regeneration of large defects of damaged tissues or organs. Magnetic nanocomposites formed by a biodegradable poly(caprolactone) (PCL) matrix and superparamagneticiron doped hydroxyapatite (FeHA) nanoparticles at different PCL/FeHA compositions have been successfully prototyped, layer on layer, through 3D bioplotting. Magnetic measurements, mechanical testing, and imaging were carried out to calibrate both model and technological processing in the magnetized scaffold prototyping. An amount of 10% w/w of magnetic FeHA nanoparticles represents a reinforcement for PCL matrix, however, a reduction of strain at failure is also…

An approach in developing 3D fiber‐deposited magnetic scaffolds for tissue engineering

AIP Conference Proceedings 2010 1255, 420

Scaffolds should possess suitable properties to play their specific role. In this work, the potential of 3D fiber deposition technique to develop multifunctional and well‐defined magnetic poly(ε‐caprolactone)/iron oxide scaffolds has been highlighted, and the effect of iron oxide nanoparticles on the biological and mechanical performances has been assessed.

Effect of scaffold architecture and BMP-2/BMP-7 delivery on in vitro bone regeneration

Journal of Materials Science: Materials in Medicine 2010 Volume 21, Issue 11, Pages 2999-3008

The aim of this study was to develop 3-D tissue engineered constructs that mimic the in vivo conditions through a self-contained growth factor delivery system. A set of nanoparticles providing the release of BMP-2 initially followed by the release of BMP-7 were incorporated in poly(ε-caprolactone) scaffolds with different 3-D architectures produced by 3-D plotting and wet spinning. The release patterns were: each growth factor alone, simultaneous, and sequential. The orientation of the fibers did not have a significant effect on the kinetics of release of the model protein BSA; but affected proliferation of bone marrow mesenchymal stem cells. Cell proliferation…

Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study

The Lancet 2010 Volume 376, Issue 9739, Pages 440-448

Background A common approach for tissue regeneration is cell delivery, for example by direct transplantation of stem or progenitor cells. An alternative, by recruitment of endogenous cells, needs experimental evidence. We tested the hypothesis that the articular surface of the synovial joint can regenerate with a biological cue spatially embedded in an anatomically correct bioscaffold. Methods In this proof of concept study, the surface morphology of a rabbit proximal humeral joint was captured with laser scanning and reconstructed by computer-aided design. We fabricated an anatomically correct bioscaffold using a composite of poly-ɛ-caprolactone and hydroxyapatite. The entire articular surface of unilateral…

Anatomically shaped tooth and periodontal regeneration by cell homing

Journal of Dental Research 2010 Volume 89, Issue 8, Pages 842-847

Tooth regeneration by cell delivery encounters translational hurdles. We hypothesized that anatomically correct teeth can regenerate in scaffolds without cell transplantation. Novel, anatomically shaped human molar scaffolds and rat incisor scaffolds were fabricated by 3D bioprinting from a hybrid of poly-ε-caprolactone and hydroxyapatite with 200-µm-diameter interconnecting microchannels. In each of 22 rats, an incisor scaffold was implanted orthotopically following mandibular incisor extraction, whereas a human molar scaffold was implanted ectopically into the dorsum. Stromal-derived factor-1 (SDF1) and bone morphogenetic protein-7 (BMP7) were delivered in scaffold microchannels. After 9 weeks, a putative periodontal ligament and new bone regenerated at the interface…

A micro-scale surface-structured PCL scaffold fabricated by a 3D plotter and a chemical blowing agent

Journal of Biomaterials Science, Polymer Edition 2010 Volume 21, Issue 2, Pages 159-170

To study cell responses, polymeric scaffolds with a controllable pore size and porosity have been fabricated using rapid-prototyping methods. However, the scaffolds fabricated by rapid prototyping have very smooth surfaces, which tend to discourage initial cell attachment. Initial cell attachment, migration, differentiation and proliferation are strongly dependent on the chemical and physical characteristics of the scaffold surface. In this study, we propose a three-dimensional (3D) plotting method supplemented with a chemical blowing agent to produce a surface-modified 3D scaffold in which the surface is inscribed with nano- and micro-sized pores. The chemically-blown 3D polymeric scaffold exhibited positive qualities, including the…

Fabrication and characterization of 3D scaffold using 3D plotting system

Chinese Science Bulletin 2010 Volume 55, Issue 1, Pages 94-98

In this paper, we design and fabricate a 3D scaffold using rapid prototyping (RP) technology for tissue engineering. The scaffold should have a three-dimensional interconnected pore network. We fabricate a polycaprolactone (PCL) scaffold with interconnecting pores and uniform porosity for cell ingrowth using a 3D plotting system. In order to keep the three dimensional shape under mechanical loading while implanted, we design an oscillating nozzle system to increase elastic modulus and yield strength of PCL strand. We characterize the influence of pore geometry, compressive modulus of the scaffold, elastic modulus and yield strength of the strand using SEM, dynamical mechanical…

Tissue Formation and Vascularization in Anatomically Shaped Human Joint Condyle Ectopically in Vivo

Tissue Engineering Part A 2009 Volume 15, Issue 12, Pages 3923-3930

Scale-up of bioengineered grafts toward clinical applications is a challenge in regenerative medicine. Here, we report tissue formation and vascularization of anatomically shaped human tibial condyles ectopically with a dimension of 20 × 15 × 15 mm3. A composite of poly-ɛ-caprolactone and hydroxyapatite was fabricated using layer deposition of three-dimensional interlaid strands with interconnecting microchannels (400 μm) and seeded with human bone marrow stem cells (hMSCs) with or without osteogenic differentiation. An overlaying layer (1 mm deep) of poly(ethylene glycol)-based hydrogel encapsulating hMSCs or hMSC-derived chondrocytes was molded into anatomic shape and anchored into microchannels by gel infusion. After 6 weeks of subcutaneous implantation in athymic rats,…

3D polycaprolactone scaffolds with controlled pore structure using a rapid prototyping system

Journal of Materials Science: Materials in Medicine 2009 Volume 20, Issue 1, Pages 229-234

Designing a three-dimensional (3-D) ideal scaffold has been one of the main goals in biomaterials and tissue engineering, and various mechanical techniques have been applied to fabricate biomedical scaffolds used for soft and hard tissue regeneration. Scaffolds should be biodegradable and biocompatible, provide temporary support for cell growth to allow cell adhesion, and consist of a defined structure that can be formed into customized shapes by a computer-aided design system. This versatility in preparing scaffolds gives us the opportunity to use rapid prototyping devices to fabricate polymeric scaffolds. In this study, we fabricated polycaprolactone scaffolds with interconnecting pores using a…

Three-Dimensional Plotter Technology for Fabricating Polymeric Scaffolds with Micro-grooved Surfaces

Journal of Biomaterials Science, Polymer Edition 2009 Volume 20, Issue 14, Pages 2089-2101
J. Son G. H. Kim

Various mechanical techniques have been used to fabricate biomedical scaffolds, including rapid prototyping (RP) devices that operate from CAD files of the target feature information. The three-dimensional (3-D) bio-plotter is one RP system that can produce design-based scaffolds with good mechanical properties for mimicking cartilage and bones. However, the scaffolds fabricated by RP have very smooth surfaces, which tend to discourage initial cell attachment. Initial cell attachment, migration, differentiation and proliferation are strongly dependent on the chemical and physical characteristics of the scaffold surface. In this study, we propose a new 3-D plotting method supplemented with a piezoelectric system for…

Hybrid Process for Fabricating 3D Hierarchical Scaffolds Combining Rapid Prototyping and Electrospinning

Macromolecular Rapid Communications 2008 Volume29, Issue19, Pages 1577-1581

An ideal scaffold should have good mechanical properties and provide a biologically functional implant site. A rapid prototyping system has been introduced as a good method of fabricating 3D scaffolds that mimic the structure in the human body. However, the scaffolds have strands that are too smooth and a pore size that is too large relative to the seeded cells and present unfavorable conditions for initial cell attachment. To overcome these problems, we propose a hybrid technology combining a 3D rapid prototyping system and an electrospinning process to produce a hierarchical 3D biomedical scaffold. The resulting structure consists of alternating…

3D Plotted PCL Scaffolds for Stem Cell Based Bone Tissue Engineering

Macromolecular Symposia 2008 Volume 269, Issue 1, Pages 92-99

The ability to control the architecture and strength of a bone tissue engineering scaffold is critical to achieve a harmony between the scaffold and the host tissue. Rapid prototyping (RP) technique is applied to tissue engineering to satisfy this need and to create a scaffold directly from the scanned and digitized image of the defect site. Design and construction of complex structures with different shapes and sizes, at micro and macro scale, with fully interconnected pore structure and appropriate mechanical properties are possible by using RP techniques. In this study, RP was used for the production of poly(ε-caprolactone) (PCL) scaffolds….

Dynamic Co-Seeding of Osteoblast and Endothelial Cells on 3D Polycaprolactone Scaffolds for Enhanced Bone Tissue Engineering

Journal of Bioactive and Compatible Polymers 2008 Volume 23, No. 3, Pages 227-243

Tissue engineered scaffolds must have an organized and repeatable microstructure which enables cells to assemble in an ordered matrix that allows adequate nutriental perfusion. In this work, to evaluate the reciprocal cell interactions of endothelial and osteoblast-like cells, human osteoblast-like cells (MG63) and Human Umbilical Vein Endothelial Cells (HUVEC) were co-seeded onto 3D geometrically controlled porous poly(ε-caprolactone) (PCL) and cultured by means of a rotary cell culture system (RCCS-4DQ). In our dynamic co-culture system, the lack of significant enhancement of osteoblast ALP activity and ECM production indicated that the microgravity conditions of the rotary system affected the cells by favoring…