PLGA/PEG-hydrogel composite scaffolds with controllable mechanical properties (original) (raw)
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Reinforcement of Mono- and Bi-layer Poly(Ethylene Glycol) Hydrogels with a Fibrous Collagen Scaffold
Annals of Biomedical Engineering, 2015
Biomaterial-based tissue engineering strategies hold great promise for osteochondral tissue repair. Yet significant challenges remain in joining highly dissimilar materials to achieve a biomimetic, mechanically robust design for repairing interfaces between soft tissue and bone. This study sought to improve interfacial properties and function in a bilayer, multi-phase hydrogel interpenetrated with a fibrous collagen scaffold. 'Soft' 10% (w/w) and 'stiff' 30% (w/w) PEGDM was formed into mono-or bilayer hydrogels possessing a sharp diffusional interface. Hydrogels were evaluated as single-(hydrogel only) or multi-phase (hydrogel+fibrous scaffold penetrating throughout the stiff layer and extending >500μm into the soft layer). Including a fibrous scaffold into both soft and stiff single-phase hydrogels significantly increased tangent modulus and toughness and decreased lateral expansion under compressive loading. In multi-phase hydrogels, finite element simulations predict substantially reduced stress and strain gradients across the soft-stiff hydrogel interface. When combining two low moduli constituent material, composites theory poorly predicts the observed, large modulus increases. These results suggest material structure associated with the fibrous scaffold penetrating within the PEG hydrogel as the major contributor to improved properties and function-the hydrogel bore compressive loads and the 3D fibrous scaffold was loaded in tension thus resisting lateral expansion.
An in situ forming collagen–PEG hydrogel for tissue regeneration
Acta Biomaterialia, 2012
There are limited options for surgeons to repair simple or complex tissue defects due to injury, illness or disease. Consequently, there are few treatments for many serious ailments, including neural-related injuries, myocardial infarction and focal hyaline cartilage defects. Tissue-engineered scaffolds offer great promise for addressing these wide-ranging indications; however, there are many considerations that need to be made when conceptualizing a product. For many applications, an in situ forming scaffold that could completely fill defects with complex geometries, adhere to adjacent tissues and foster cell proliferation would be ideal. Additionally, the scaffold would preferably have tailored mechanical properties similar to native tissues and highly controllable gelation kinetics, and would not require an external trigger, such as ultraviolet light, for gelation. We have developed a unique injectable hydrogel system composed of collagen and multi-armed poly(ethylene glycol) (PEG) that meets all of these criteria. The collagen component enables cellular adhesion and permits enzymatic degradation, while the multiarmed PEG component has amine-reactive chemistry that also binds proteins/tissue and is hydrolytically degradable. We have characterized the mechanical properties, swelling, degradation rates and cytocompatibility of these novel hydrogels. The hydrogels demonstrated tunable mechanics, variable swelling and suitable degradation profiles. Cells adhered and proliferated to near confluence on the hydrogels over 7 days. These data suggest that these collagen and PEG hydrogels exhibit the mechanical, physical and biological properties suitable for use as an injectable tissue scaffold for the treatment of a variety of simple and complex tissue defects.
Journal of Biomaterials Science, Polymer Edition
The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (DL-lactic-co-glycolic acid), (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. 29 There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37°C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p < 0.05). The formulation also sintered at 37°C following injection through a needle, demonstrating its injectable potential. The scaffolds demonstrated cytocompatibility, with increased cell numbers observed over an 8-35 day study period. Von Kossa and immunostaining of the hMSC-scaffolds confirmed their 36 osteogenic potential with the ability to sinter at 37°C in situ.
Polymers
The aim of this study was to report the fabrication of porous scaffolds with pre-designed internal pores using a fused deposition modeling (FDM) method. Polycaprolactone (PCL) is a suitable material for the FDM method due to the fact it can be melted and has adequate flexural modulus and strength to be formed into a filament. In our study, the filaments of methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) having terminal groups of carboxylic acid were deposited layer by layer. Raw materials having a weight ratio of hydroxyapatite (HAp) to polymer of 1:2 was used for FDM. To promote cell adhesion, amino groups of the Arg-Gly-Asp(RGD) peptide were condensed with the carboxylic groups on the surface of the fabricated scaffold. Then the scaffold was infiltrated with hydrogel of glycidyl methacrylate hyaluronic acid loading with 10 ng/mL of TGF-β1 and photo cross-linked on the top of the scaffolds. Serious tests of mechanical and biological properties were performed in vitro. HAp was found to significantly increase the compressive strength of the porous scaffolds. Among three orientations of the filaments, the lay down pattern 0 • /90 • scaffolds exhibited the highest compressive strength. Fluorescent staining of the cytoskeleton found that the osteoblast-like cells and stem cells well spread on RGD-modified PEG-PCL film indicating a favorable surface for the proliferation of cells. An in vivo test was performed on rabbit knee. The histological sections indicated that the bone and cartilage defects produced in the knees were fully healed 12 weeks after the implantation of the TGF-β1 loaded hydrogel and scaffolds, and regenerated cartilage was hyaline cartilage as indicated by alcian blue and periodic acid-schiff double staining.
Polymer, 2009
Aligned nanofibrous blends of poly (D, L-lactide-co-glycolide) (PLGA) and collagen with various PLGA/ collagen compositions (80/20, 65/35 and 50/50) were fabricated by electrospinning and characterized for bone tissue engineering. Morphological characterization showed that the addition of collagen to PLGA resulted in narrowing of the diameter distribution and a reduction in average diameter. Differential scanning calorimetric (DSC) studies showed that the triple helix structure of the native collagen was not destroyed during the fabrication process. However, the blending had a marked effect on the overall enthalpy of the blends, whereby the total enthalpy decreased as the collagen content decreased. Thermogravimetric analysis showed the addition of collagen increased the hydrophilicity of the scaffolds. The crosslinking of collagen to increase the biostability was done using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) in ethanol and an overall w25% degree of crosslinking was achieved. The EDC crosslinking had little effect on the nanofibrous morphology of the 80/20 blend system; however, the nanofibrous features were compromised to some extent at higher collagen concentrations. The mechanical characterization under dry and wet conditions showed that increasing collagen content resulted in a tremendous decrease in the mechanical properties. However, crosslinking resulted in the increase in elastic modulus from 47 MPa to 83 MPa for the wet PLGA/Collagen 80/20 blend system, with little effect on the tensile strength. In conclusion, the aligned nanofibrous scaffold used in this study constitutes a promising material for bone tissue engineering.
Biomedical Materials, 2014
Thermosensitive hydrogels are renowned carriers that are used to deliver a variety of drugs with the aim of combating diseases. In this study, the injectability of thermosensitive hydrogels comprised of poly(ethylene glycol)-poly(lactic acid-co-glycolic acid)-poly(ethylene glycol) (PEG-PLGA-PEG, PELGE) and hydroxyapatite (HA) were examined for their ability to deliver bone morphological protein 2 (BMP-2). The physicochemical characteristics of PELGE, HA, and PELGE/HA hydrogel composites were investigated by 1 H NMR, GPC, FTIR, XRD, SEM, and TEM. The rheological properties, injectability, in vitro degradation, and in vivo biocompatibility were investigated. The hydrogel with a weight ratio of 4:6 of polymer to HA was found to be resistant to auto-catalyzed degradation of acidic monomers (LA, GA) for a period of 70 days owing to the presence of alkaline HA. Injectability was quantitatively determined by the ejected weight of the hydrogel composite at room temperature and was a close match to the weight amount predetermined by the syringe pump. The results not only revealed that the PELGE/HA hydrogel composite presented a minor tissue response in the subcutis of ICR mice at eight weeks, but they also indicated an acceptable tolerance of the hydrogel composite in animals. Thus, PELGE/HA hydrogel composite is expected to be a promising injectable orthopedic substitute because of its desirable thermosensitivity and injectability.