In vitro and in vivo degradation behavior of poly(trimethylene carbonate-co-d,l-lactic acid) copolymer.
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ABSTRACT:
SUBMITTER: Ma Z
PROVIDER: S-EPMC5544909 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
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Project description:Poly(lactic-co-glycolic acid) (PLGA) has been used in the field of tissue engineering as a scaffold due to its good biocompatibility, biodegradability and mechanical strength. With the aim to explore the degradability of PLGA electrospun nonwoven structures for oral mucosa tissue engineering applications, non-irradiated and gamma irradiated nonwovens were immersed in three different solutions, in which simulated body fluid (SBF) and artificial saliva are important for future oral mucosa tissue engineering. The nonwovens were immersed for 7, 15 and 30 days in SBF, culture media (DMEM) and artificial saliva at 37 °C. Before immersion in the solutions, the dosage of 15 kGy was applied for sterilization in one assay and compared with non-irradiated samples at the same timepoints. Samples were characterized using different techniques such as scanning electron microscopy (SEM), differential scanning calorimetric (DSC) and gel permeation chromatography (GPC) to evaluate the nonwoven degradation and Fourier-transform infrared spectroscopy (FTIR) to evaluate the chain scissions. Our results showed that PLGA nonwovens were constituted by semicrystalline fibers with moderate degradation properties up to thirty days. The non-irradiated samples exhibited slower kinetics of degradation than irradiated nonwovens. For immersion times longer than 7 days in the three different solutions, the mean diameter of irradiated fibers stayed in the same range, but significantly different from the control sample. On non-irradiated samples, the degradation kinetics was slower and the plateau in the diameter value was only attained after 30 days of immersion in the fluids. Plasticization (fluid absorption into the fiber structure) occurred in the bulk material, as confirmed by a decrease in Tg observed by DSC analyses of non-irradiated and irradiated nonwovens, in comparison with the respective controls. In addition, artificial saliva showed a higher capacity of influencing PLGA crystallization than SBF and DMEM. FTIR analyses showed typical PLGA chemical functional groups changes. These results will be important for future application of those PLGA electrospun nonwovens for oral mucosa regeneration.
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Project description:Biodegradable polymer/hydroxyapatite (HA) composites are desired for skeletal tissue engineering. When engineered with thermal-responsive shape memory properties, they may be delivered in a minimally invasive temporary shape and subsequently triggered to conform to a tissue defect. Here we report the shape memory properties of thermoplastic amphiphilic poly(D,L-lactic acid-co-ethylene glycol-co-D,L-lactic acid) (PELA, 120 kDa) and HA-PELA composites. These materials can be cold-deformed and stably fixed into temporary shapes at room temperature and undergo rapid shape recovery (< 3 s) at 50 °C. Stable fixation (>99% fixing ratio) of large deformations is achieved at -20 °C. While the shape recovery from tensile deformations slows with higher HA contents, all composites (up to 20 wt% HA) achieve high shape recovery (>90%) upon 10-min equilibration at 50 °C. The permanent shapes of HA-PELA can be reprogramed at 50 °C, and macroporous shape memory scaffolds can be fabricated by rapid prototyping.
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Project description:INTRODUCTION: Inflammation plays a key role in the progression of intervertebral disc degeneration, a condition strongly implicated as a cause of lower back pain. The objective of this study was to investigate the therapeutic potential of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with interleukin-1 receptor antagonist (IL-1ra) for sustained attenuation of interleukin-1 beta (IL-1?) mediated degradative changes in the nucleus pulposus (NP), using an in vitro model. METHODS: IL-1ra was encapsulated in PLGA microspheres and release kinetics were determined over 35 days. NP agarose constructs were cultured to functional maturity and treated with combinations of IL-1? and media conditioned with IL-1ra released from microspheres at intervals for up to 20 days. Construct mechanical properties, glycosaminoglycan content, nitrite production and mRNA expression of catabolic mediators were compared to properties for untreated constructs using unpaired Student's t-tests. RESULTS: IL-1ra release kinetics were characterized by an initial burst release reducing to a linear release over the first 10 days. IL-1ra released from microspheres attenuated the degradative effects of IL-1? as defined by mechanical properties, glycosaminoglycans (GAG) content, nitric oxide production and mRNA expression of inflammatory mediators for 7 days, and continued to limit functional degradation for up to 20 days. CONCLUSIONS: In this study, we successfully demonstrated that IL-1ra microspheres can attenuate the degradative effects of IL-1? on the NP for extended periods. This therapeutic strategy may be appropriate for treating early-stage, cytokine-mediated disc degeneration. Ongoing studies are focusing on testing IL-1ra microspheres in an in vivo model of disc degeneration, as a prelude to clinical translation.
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Project description:Bone substitute materials have witnessed tremendous development over the past decades and autogenous bone may still be considered the gold standard for many clinicians and clinical approaches in order to rebuild and restore bone defects. However, a plethora of novel xenogenic and synthetic bone substitute materials have been introduced in recent years in the field of bone regeneration. As the development of bone is actually a calcification process within a collagen fiber arrangement, the use of scaffolds in the formation of fibers may offer some advantages, along with additional handling characteristics. This review focuses on material characteristics and degradation behavior of electrospun biodegradable polyester scaffolds. Furthermore, we concentrated on the preclinical in vivo performance with regard to bone regeneration in preclinical studies. The major findings are as follows: Scaffold composition and architecture determine its biological behavior and degradation characteristics; The incorporation of inorganic substances and/or organic substances within composite scaffolds enhances new bone formation; L-poly(lactic acid) and poly(lactic-co-glycolic acid) composite scaffolds, especially when combined with basic substances like hydroxyapatite, tricalcium phosphate or demineralized bone powder, seem not to induce inflammatory tissue reactions in vivo.
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Project description:A mixed oxide of titania-silica oxides (TixSiy oxides) was successfully prepared via the sol-gel technique from our previous work. The use of TixSiy oxides to improve the mechanical properties, photocatalytic efficiency, antibacterial property, permeability tests, and biodegradability of polylactic acid (PLA) was demonstrated in this study. The influence of different types and contents of TixSiy oxides on crystallization behavior, mechanical properties, thermal properties, and morphological properties was presented. In addition, the effect of using TixSiy oxides as a filler in PLA composites on these properties was compared with the use of titanium dioxide (TiO2), silicon dioxide (SiO2), and TiO2SiO2. Among the prepared biocomposite films, the PLA/TixSiy films showed an improvement in the tensile strength and Young's modulus (up to 5% and 31%, respectively) in comparison to neat PLA films. Photocatalytic efficiency to degrade methylene blue (MB), hydrolytic degradation, and in vitro degradation of PLA are significantly improved with the addition of TixSiy oxides. Furthermore, PLA with the addition of TixSiy oxides exhibited an excellent antibacterial effect on Gram-negative bacteria (Escherichia coli or E. coli) and Gram-positive bacteria (Staphylococcus aureus or S. aureus), indicating the improved antimicrobial effectiveness of PLA composites. Importantly, up to 5% TixSiy loading could promote more PLA degradation via the water absorption ability of mixed oxides. According to the research results, the PLA composite films produced with TixSiy oxide were transparent, capable of screening UV radiation, and exhibited superior antibacterial efficacy, making them an excellent food packaging material.
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Project description:BackgroundPoly(trimethylene carbonate) (PTMC) has wide biomedical applications in the field of tissue engineering, due to its biocompatibility and biodegradability features. Its common manufacturing involves photofabrication, such as stereolithography (SLA), which allows the fabrication of complex and controlled structures. Despite the great potential of SLA-fabricated scaffolds, very few examples of PTMC-based drug delivery systems fabricated using photo-fabrication can be found ascribed to light-triggered therapeutics instability, degradation, side reaction, binding to the macromers, etc. These concerns severely restrict the development of SLA-fabricated PTMC structures for drug delivery purposes.MethodsIn this context, we propose here, as a proof of concept, to load a drug model (dexamethasone) into electrospun fibers of poly(lactic acid), and then to integrate these bioactive fibers into the photo-crosslinkable resin of PTMC to produce hybrid films. The hybrid films' properties and drug release profile were characterized; its biological activity was investigated via bone marrow mesenchymal stem cells culture and differentiation assays.ResultsThe polymer/polymer hybrids exhibit improved properties compared with PTMC-only films, in terms of mechanical performance and drug protection from UV denaturation. We further validated that the dexamethasone preserved its biological activity even after photoreaction within the PTMC/poly(lactic acid) hybrid structures by investigating bone marrow mesenchymal stem cells proliferation and osteogenic differentiation.ConclusionThis study demonstrates the potential of polymer-polymer scaffolds to simultaneously reinforce the mechanical properties of soft matrices and to load sensitive drugs in scaffolds that can be fabricated via additive manufacturing.
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