3D Bioplotter Research Papers

Displaying all papers about Drug Release (29 results)

3D Bioprinting of the Sustained Drug Release Wound Dressing with Double-Crosslinked Hyaluronic-Acid-Based Hydrogels

Polymers 2019 Volume 11, Issue 10, Article 1584

Hyaluronic acid (HA)-based hydrogels are widely used in biomedical applications due to their excellent biocompatibility. HA can be Ultraviolet (UV)-crosslinked by modification with methacrylic anhydride (HA-MA) and crosslinked by modification with 3,3′-dithiobis(propionylhydrazide) (DTP) (HA-SH) via click reaction. In the study presented in this paper, a 3D-bioprinted, double-crosslinked, hyaluronic-acid-based hydrogel for wound dressing was proposed. The hydrogel was produced by mixing HA-MA and HA-SH at different weight ratios. The rheological test showed that the storage modulus (G’) of the HA-SH/HA-MA hydrogel increased with the increase in the HA-MA content. The hydrogel had a high swelling ratio and a high controlled degradation…

3D printing of layered mesoporous bioactive glass/sodium alginate-sodium alginate scaffolds with controllable dual-drug release behaviors

Biomedical Materials 2019 Volume 14, Article 065011

Scaffolds with controlled drug release are valuable for bone tissue engineering, but constructing the scaffolds with controllable dual-drug release behaviors is still a challenge. In this study, layered mesoporous bioactive glass/sodium alginate-sodium alginate (MBG/SA–SA) scaffolds with controllable dual-drug release behaviors were fabricated by 3D printing. The porosity and compressive strength of three-dimensional (3D) printed MBG/SA–SA scaffolds by cross-linking are about 78% and 4.2 MPa, respectively. As two model drugs, bovine serum albumin (BSA) and ibuprofen (IBU) were separately loaded in SA layer and MBG/SA layer, resulting in a relatively fast release of BSA and a sustained release of IBU. Furthermore,…

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…

3D-printed scaffolds of biomineralized hydroxyapatite nanocomposite on silk fibroin for improving bone regeneration

Applied Surface Science 2019 Volumes 467–468, Pages 345-353

In an attempt to fabricate biomimetic bone repair scaffolds and improve bone regeneration point of view, we have three dimensionally printed porous scaffolds with biomineralized hydroxyapatite/silk fibroin nanocomposites. SF/HA composite particles were firstly produced via an in-situ mineral precipitation process when SF molecules were served as templates.. Microscopy observations of SF/HA showed homogeneous morphology and narrowly distributed size. By using sodium alginate (SA) as paste binder, scaffolds with different contents of SF/HA were subsequently 3D-printed under proper conditions. All the scaffolds were porous with 3D interconnected large pores (size ~400 μm) and an overall porosity about 70%, combined with a relative…

Extrudability analysis of drug loaded pastes for 3D printing of modified release tablets

International Journal of Pharmaceutics 2019 Volume 554, Pages 292-301

The rheological characteristics of pastes for 3D printing of tablets may not be described fully by the traditional rheological tests generally used for other pastes. In the present study, extrudability testing of carbopol based 3D printing pastes was performed to establish a constitutive rheological model for micro-extrusion. This model was developed for pastes that exhibit a non-linear plasto-viscoelastic behavior and follow the generalized Herschel–Bulkley flow rule. An analytical model was applied to extrudability data obtained by micro-extrusion through nozzles of 0.4 and 0.6 mm diameters. For this purpose, nineteen pastes were prepared per a fractional factorial design using various concentrations of…

Development of mechanistic models to identify critical formulation and process variables of pastes for 3D printing of modified release tablets

International Journal of Pharmaceutics 2019 Volume 555, Pages 109-123

The future of pharmaceutical manufacturing may be significantly transformed by 3-dimensional (3D) printing. As an emerging technology, the indicators of quality for materials and processes used in 3D printing have not been fully established. The objective of this study was to identify the critical material attributes of semisolid paste formulations filled into cartridges for 3D printing of personalized medicine. Nineteen semisolid formulations were prepared per a fractional factorial design with three replicates of the center point. The variables investigated included percent loading of API and various soluble and insoluble excipients. Pastes were characterized for viscoelastic characteristics during the 3D printing…

Effect of Dexamethasone on Room Temperature Three-Dimensional Printing, Rheology, and Degradation of a Low Modulus Polyester for Soft Tissue Engineering

ACS Biomaterials Science & Engineering 2019 Volume 5, Issue 2, Pages 846–858

Three-dimensional (3D) printing has enabled benchtop fabrication of customized bioengineered constructs with intricate architectures. Various approaches are being explored to enable optimum integration of such constructs into the physiological environment including addition of bioactive fillers. In this work, we incorporated a corticosteroid drug, dexamethasone (Dex), in a low modulus polyester (SC5050) and examined the effect of Dex incorporation on solvent-, initiator-, and monomer-free pneumatic extrusion-based 3D printing of the polymer. Dex–SC5050 interactions were characterized by plotting thermodynamic binary phase diagrams based on the Flory–Huggins theory. The effect of Dex composition on the 3D printability of the SC5050 polyester was examined…

On-demand manufacturing of immediate release levetiracetam tablets using pressure-assisted microsyringe printing

European Journal of Pharmaceutics and Biopharmaceutics 2019 Volume 134, Pages 29-36

Fast and accurate manufacturing of individually tailored solid dosage forms is one of the main challenges for personalized medicine. The use of 3D printers has recently been studied to determine their suitability for personalized drug manufacturing. In the current work, formulations free of organic solvents were developed for a pressure-assisted microsyringe printing method (PAM). The water soluble polymer polyvinyl alcohol-polyethylene glycol graft copolymer (PVA-PEG) was used as matrix, while levetiracetam (LEV) was used as model drug. Furthermore, the influence of a second polymer, polyvinylpyrrolidone-vinyl acetate copolymer (PVP-PVAc) on the properties of the printed tablets was investigated. Tablets were printed using…

3D Printing Bioactive PLGA Scaffolds Using DMSO as a Removable Solvent

Bioprinting 2018 Volume 10, June 2018, Article e00038

Present bioprinting techniques lack the methodology to print with bioactive materials that retain their biological functionalities. This constraint is due to the fact that extrusion-based printing of synthetic polymers is commonly performed at very high temperatures in order to achieve desired mechanical properties and printing resolutions. Consequently, current methodology prevents printing scaffolds embedded with bioactive molecules, such as growth factors. With the wide use of mesenchymal stem cells (MSCs) in regenerative medicine research, the integration of growth factors into 3D printed scaffolds is critical because it can allow for inducible MSC differentiation. We have successfully incorporated growth factors into extrusion…

Heparin/Poly-L-lysine-coated 3D-printed PLGA scaffolds as drug carriers for local immune modulation in bone regeneration

Society for Biomaterials Annual Meeting and Exposition 2018 Presentation 584

Immune responses after injury play a critical role in bone regeneration. Initiation of inflammation at early stages of repair triggers tissue formation and remodeling; however, uncontrolled inflammation underlies a catabolic effect on tissues as commonly seen in arthritis where inflammation breaks down tissues and hinders regeneration. Our ultimate goal is to design a novel approach on bone scaffolds for which biodegradable scaffolds are loaded with inflammatory cytokines for local immunomodulation as well as bone regeneration. We employed nanoparticles (NPs) composed of heparin (Hep) and poly-L-lysine (PLL) as cytokine drug carriers adhered on 3D-printed poly(lactic-co-glycolic acid) (PLGA) scaffolds. The entire drug…

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.

Comparison of the degradation behavior of PLGA scaffolds in micro-channel, shaking, and static conditions

Biomicrofluidics 2018 Volume 12, Article 034106

Degradation of scaffolds is an important problem in tissue regeneration management. This paper reports a comparative study on degradation of the printed 3D poly (lactic-co-glycolic acid) scaffold under three conditions, namely, micro-channel, incubator static, and incubator shaking in the phosphate buffer saline (PBS) solution. In the case of the micro-channel condition, the solution was circulated. The following attributes of the scaffold and the solution were measured, including the mass or weight loss, water uptake, morphological and structural changes, and porosity change of the scaffold and the pH value of the PBS solution. In addition, shear stress in the scaffold under…

PLGA Drug Release

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…

3D printed, controlled release, tritherapeutic tablet matrix for advanced anti-HIV-1 drug delivery

European Journal of Pharmaceutics and Biopharmaceutics 2018 In Press, Corrected Proof

Purpose A 3D-Bioplotter® was employed to 3D print (3DP) a humic acid-polyquaternium 10 (HA-PQ10) controlled release fixed dose combination (FDC) tablet comprising of the anti-HIV-1 drugs, efavirenz (EFV), tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Methods Chemical interactions, surface morphology and mechanical strength of the FDC were ascertained. In vitro drug release studies were conducted in biorelevant media followed by in vivo study in the large white pigs, in comparison with a market formulation, Atripla®. In vitro-in vivo correlation of results was undertaken. Results EFV, TDF and FTC were successfully entrapped in the 24-layered rectangular prism-shaped 3DP FDC with a…

3D-printed IFN-γ-loading calcium silicate-β-tricalcium phosphate scaffold sequentially activates M1 and M2 polarization of macrophages to promote vascularization of tissue engineering bone

Acta Biomaterialia 2018 Volume 71, Pages 96-107

To promote vascularization of tissue-engineered bone, IFN-γ polarizing macrophages to M1 was loaded on 5% calcium silicate/β-tricalcium phosphate (CaSiO3-β-TCP) scaffolds. IFN-γ and Si released from the scaffold were designed to polarize M1 and M2 macrophages, respectively. β-TCP, CaSiO3-β-TCP, and IFN-γ@CaSiO3-β-TCP were fabricated and biocompatibilities were evaluated. Polarizations of macrophages were detected by flow cytometry. Human umbilical vein endothelial cells with GFP were cultured and induced on Matrigel with conditioned culture medium extracted from culture of macrophages loaded on scaffolds for evaluating angiogenesis. Four weeks after the scaffolds were subcutaneously implanted into C57B1/6, vascularization was evaluated by visual observation, hematoxylin and…

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…

3D scaffold with effective multidrug sequential release against bacteria biofilm

Acta Biomaterialia 2016 Volume 49, Pages 113–126

Bone infection is a feared complication following surgery or trauma that remains as an extremely difficult disease to deal with. So far, the outcome of therapy could be improved with the design of 3D implants, which combine the merits of osseous regeneration and local multidrug therapy so as to avoid bacterial growth, drug resistance and the feared side effects. Herein, hierarchical 3D multidrug scaffolds based on nanocomposite bioceramic and polyvinyl alcohol (PVA) prepared by rapid prototyping with an external coating of gelatin-glutaraldehyde (Gel-Glu) have been fabricated. These 3D scaffolds contain three antimicrobial agents (rifampin, levofloxacin and vancomycin), which have been…

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…

3D-printed hierarchical scaffold for localized isoniazid/rifampin drug delivery and osteoarticular tuberculosis therapy

Acta Biomaterialia 2015 Volume 16, Pages 145–155

After surgical treatment of osteoarticular tuberculosis (TB), it is necessary to fill the surgical defect with an implant, which combines the merits of osseous regeneration and local multi-drug therapy so as to avoid drug resistance and side effects. In this study, a 3D-printed macro/meso-porous composite scaffold is fabricated. High dosages of isoniazid (INH)/rifampin (RFP) anti-TB drugs are loaded into chemically modified mesoporous bioactive ceramics in advance, which are then bound with poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) through a 3D printing procedure. The composite scaffolds show greatly prolonged drug release time compared to commercial calcium phosphate scaffolds either in vitro or in vivo….

The preliminary performance study of the 3D printing of a tricalcium phosphate scaffold for the loading of sustained release anti-tuberculosis drugs

Journal of Materials Science 2015 Volume 50, Issue 5, Pages 2138-2147

In the surgical treatment of tuberculosis of the bones, excision of the lesion site leaves defects in the bone structure. Recent research has shown benefits for bone tissue support, such as tricalcium phosphate, as regrowth materials. These biocompatible engineering materials have good bone inductivity and biologic mechanical performance. The goal of this study was to evaluate the use of 3D printing, a new technology, to design and build 3-dimensional support structures for use in grafting at lesion sites and for use in embedding the sustained release anti-tuberculosis drugs Rifampin and Isoniazid and determine the in vivo performance of these structures….

Use of the polycation polyethyleneimine to improve the physical properties of alginate-hyaluronic acid hydrogel during fabrication of tissue repair scaffolds

Journal of Biomaterials Science, Polymer Edition 2015 Volume 26, Issue 7, Pages 433-445

Recently alginate-based tissue repair scaffolds fabricated using 3D printing techniques have been extensively examined for use in tissue engineering applications. However, their physical and mechanical properties are unfavorable for many tissue engineering applications because these properties are poorly controlled during the fabrication process. Some improvement of alginate gel properties can be realized by addition of hyaluronic acid (HA), and this may also improve the ability of cells to interact with the gel. Here, we report improvement of the physical properties of alginate–HA gel scaffolds by the addition of the polycation polyethyleneimine (PEI) during the fabrication process in order to stabilize…

Fabrication of novel Si-doped Hydroxyapatite/Gelatine scaffolds by rapid prototyping for drug delivery and bone regeneration

Acta Biomaterialia 2015 Volume 15, Pages 200–209

Porous 3-D scaffolds consisting of gelatine and Si-doped hydroxyapatite were fabricated at room temperature by rapid prototyping. Microscopic characterization revealed a highly homogeneous structure, showing the pre-designed porosity (macroporosity) and a lesser in-rod porosity (microporosity). The mechanical properties of such scaffolds are close to those of trabecular bone of the same density. The biological behavior of these hybrid scaffolds is greater than that of pure ceramic scaffolds without gelatine, increasing pre-osteoblastic MC3T3-E1 cell differentiation (matrix mineralization and gene expression). Since the fabrication process of these structures was carried out at mild conditions, an antibiotic (vancomycin) was incorporated in the slurry…

3D-printed dimethyloxallyl glycine delivery scaffolds to improve angiogenesis and osteogenesis

Biomaterials Science 2015 Voulme 3, Issue 8, Pages 1236-1244

Angiogenesis–osteogenesis coupling processes are vital in bone tissue engineering. Normal biomaterials implanted in bone defects have issues in the sufficient formation of blood vessels, especially in the central part. Single delivery of vascular endothelial growth factors (VEGF) to foci in previous studies did not show satisfactory results due to low loading doses, a short protein half-life and low efficiency. Development of a hypoxia-mimicking microenvironment for cells by local prolyl-4-hydroxylase inhibitor release, which can stabilize hypoxia-inducible factor 1α (HIF-1α) expression, is an alternative method. The aim of this study was to design a dimethyloxallyl glycine (DMOG) delivering scaffold composed of mesoporous…

Three-dimensionally plotted MBG/PHBHHx composite scaffold for antitubercular drug delivery and tissue regeneration

Journal of Materials Science: Materials in Medicine 2015 Volume 26, Issue 102, 102ff

A suitable drug-loaded scaffold that can postoperatively release an antituberculosis drug efficiently in a lesion area and help repair a bone defect is very important in the clinical treatment of bone tuberculosis (TB). In this study, a composite drug-loaded cylindrical scaffold was prepared by using three-dimensional printing technology in combination with the mesoporous confinement range, surface chemical groups, and gradual degradation of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate). This achieves the slow release of a drug for as long as possible. We implanted the drug-loaded compound scaffold into New Zealand rabbits’ femur defect model to study the in vivo drug release performance and osteogenic ability….

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…

Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration

Acta Biomaterialia 2014 Volume 10, Issue 5, Pages 2269–2281

In this study, we fabricated strontium-containing mesoporous bioactive glass (Sr-MBG) scaffolds with controlled architecture and enhanced mechanical strength using a three-dimensional (3-D) printing technique. The study showed that Sr-MBG scaffolds had uniform interconnected macropores and high porosity, and their compressive strength was ∼170 times that of polyurethane foam templated MBG scaffolds. The physicochemical and biological properties of Sr-MBG scaffolds were evaluated by ion dissolution, apatite-forming ability and proliferation, alkaline phosphatase activity, osteogenic expression and extracelluar matrix mineralization of osteoblast-like cells MC3T3-E1. The results showed that Sr-MBG scaffolds exhibited a slower ion dissolution rate and more significant potential to stabilize the…

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…

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…