Fabrication of novel PLA/CDHA bionanocomposite fibers for tissue engineering applications via electrospinning

The main theme here is to fabricate PLA (poly lactic-acid)/CDHA (carbonated calcium deficient hydroxyapatite) bionanocomposites, where both the constituents are biocompatible and biodegradable with one dimension in nanometer scale. Such materials are important in tissue engineering applications. The bionanocomposite fibers were fabricated via electrospinning. There are two important signatures of this paper. First, CDHA, rather than HA, is added to PLA as the second phase. As opposed to HA, CDHA mimics the bone mineral composition better and is biodegradable. Therefore, PLA/CDHA fibers should have better biodegradability while maintaining a physiological pH during degradation. To the best of our knowledge, this is the first attempt of electrospinning of such a composite. Second, the CDHA nanoparticles were synthesized using the benign low temperature biomimetic technique, the only route available for the retention of carbonate ions in the HA lattice. The structural properties, degradation behavior, bioactivity, cell adhesion, and growth capability of as-fabricated PLA/CDHA bionanocomposites were investigated. The results show that the incorporation of CDHA decreased PLA fiber diameters, accelerated PLA degradation, buffered pH decrease caused by PLA degradation, improved the bioactivity and biocompatibility of the scaffold. These results prove that PLA/CDHA bionanocomposites have the potential in tissue regeneration applications.     

多孔Nano-dHA/PLA/BCP复合支架的制备及性能研究

为改善常规的多孔聚乳酸/双相钙磷陶瓷(PLA/BCP)支架表面亲水性不佳及降解时呈酸性等不足,采用马弗炉烧结制备的BCP多孔支架浸入纳米缺钙羟基磷灰石/聚乳酸(nano-dHA/PLA)混悬液后,真空干燥得到多孔纳米缺钙羟基磷灰石/聚乳酸/双相钙磷陶瓷(nano-dHA/PLA/BCP)复合支架,利用万能测试机测试支架抗压强度,阿基米德法测定支架孔隙率,扫描电子显微镜(SEM)观察支架表面形貌,并对其保水率和体外降解过程中pH值的变化情况等进行了研究. 结果表明：多孔nano dHA/PLA/BCP复合支架表面粗糙,保水率和强度均有较大提高,在磷酸盐缓冲液（PBS）浸泡过程中pH值下降较慢,在模拟体液（SBF）中浸泡1个月后发现有较多的类骨磷灰石形成.     

Biodegradation of a silkworm silk/PLA composite

Animal silks and poly(lactic acid) (PLA) are potential materials for biomedical and bioengineering applications. Biodegradability of these materials thus is important to minimize any extra pain of patients with bone defects due to second operations for removing those non-biodegradable implants. However, the control of their biodegradability and mechanical properties is essential to ensure a smooth load transfer from a depredating implant to neo-tissue. In this study, a biodegradation test on silk/PLA biocomposites was performed. Physical and mechanical properties, pH condition of the surrounding fluid and the morphology of fractured samples were studied at specific time points. It was found that there were no significant differences between the pH values of the solution and weight loss for both pure PLA samples and silk/PLA biocomposites. Moreover, with the reinforcement of silk fiber, stiffness and ductility of PLA were enhanced and a faster biodegradation rate was observed within the 4-month biodegradation period. It can be concluded that the biodegradation rate of implants can be altered and their mechanical properties can be enhanced by incorporation of silk fiber. This is a potential solution to match with the degradation rate of PLA to the regeneration rate of neo-tissues.     

Use of DSC to Study the Degradation Behavior of PLA and PLGA Microparticles

Abstract

Poly (D, L-lactide) (PLA) and poly (D, L-lactide-co-glycolide) (PLGA) microparticles were evaluated for their in vitro degradation behavior in 0.1 M phosphate buffer pH 7.4 at 37°C. The influence of polymer characteristics, particle size, and preparation technique was investigated. Differential scanning calorimetry (DSC) was used to follow the time-dependent physical and morphological changes within the hydrated and dried microparticles, to determine the physical state of the absorbed water, and to detect penetration of buffer ions into the particle bulk. Results were compared with degradation kinetics obtained by gel permeation chromatography (GPC) and gravimetry. The latter revealed triphasic degradation profiles for R 202 and RG 755 microparticles with a mean particle size of 55 μm and 60 μm, respectively. An induction period was followed by a period of accelerated ester cleavage pre-onset of erosion and a final period of slow ester cleavage post-onset of erosion. According to DSC data the induction period is characterized by a glassy hydrated polymer matrix with a T_gH > 37°C. The induction period (t_i) correlated well with the lag-time of T_gH to reach 37°C (t_{lag 37°C}), thus confirming the importance of chain mobility for the degradation kinetic. The final decrease in the rate of ester chain cleavage post-onset of erosion turned out to be the result of an increase in matrix permeability for buffer ions inducing sodium salt formation and phase separation of the water-soluble degradation products within the particle bulk. Particle size effects depended on the preparation technique. A decrease in the degradation rate with a decrease in mean particle size was only observed when the molecular weight distribution of the polymer was not affected by the prepa ration procedure used to reduce the particle size. According to DSC data, the effect is due to a faster and more continuous release of the water-soluble degradation products from the smaller particles, thus reducing their plasticizing and autocata-lytic effects within the particle bulk.     

镁-羟基磷灰石/聚乳酸复合材料的制备及表征

为改善羟基磷灰石(HA)/聚乳酸(PLA)复合材料降解后产生的局部酸性环境,提出Mg-HA/PLA复合材料的新体系,采用溶液共混法结合注塑工艺获得Mg-HA/PLA复合材料。采用扫描电镜、X射线衍射仪分析复合材料的显微相貌及物相组成,电子拉伸试验机测试复合材料的力学性能,模拟体液浸泡分析其降解特性。结果表明,采用溶液共混结合注塑工艺可以制备该复合材料;HA与Mg在PLA基体中未出现明显的团聚;HA、Mg与PLA三者保持各自物相;与5%(质量分数)HA/PLA复合材料相比,1.5%(质量分数)Mg添加对5%(质量分数)HA/PLA复合材料的力学性能影响不明显;Mg-HA/PLA复合材料浸泡4周后的pH值为7.41,而HA/PLA复合材料则为6.95。     

镁/聚乳酸复合材料的制备与表征

为有效中和聚乳酸降解过程后的酸性,提出镁颗粒与聚乳酸的复合材料新体系。采用造粒-注塑工艺制备了3%Mg/聚乳酸(PLA)复合材料,通过扫描电镜(SEM)、X射线衍射(XRD)等手段表征了产物的微观形貌与物相组成;测试了力学性能;采用模拟体液浸泡手段研究了复合材料的降解行为。结果表明,采用造粒、注塑工艺可以制备这类复合材料,少量镁颗粒的加入对聚乳酸的力学性能影响不明显,其中拉伸强度和延伸率分别下降了6%和12.5%,但弯曲强度有所增加。聚乳酸降解后的酸性得到了有效的中和,聚乳酸浸泡30 d后的pH值为6.28,而3%Mg/PLA复合材料浸泡30 d后的pH值仅为6.85。     

In vivo biocompatibility of radiation induced acrylamide and acrylamide/maleic acid hydrogels

In vitro swelling and in vivo biocompatibility of radiation induced acrylamide (AAm) and acrylamide/maleic acid (AAm/MA) hydrogels were investigated. The swelling kinetics of AAm and AAm/MA hydrogels of are investigated in distilled water, human serum and some simulated physiological fluids such as phosphate buffer at pH 7.4, glycine-HCl buffer at pH 1.1, physiological saline solution and, some swelling and diffusion parameters have been calculated. AAm and AAm/MA hydrogels were subcutaneously implanted in rats for up to 10 weeks and the tissue response to these implants was studied. Histological analysis indicated that tissue reaction at the implant site progressed from an initial acute inflammatory response characterized. No necrosis, tumorigenesis or infection was observed at the implant site up to 10 week. In vivo studies indicated that the radiation induced acrylamide and acrylamide/maleic acid hydrogels were found to be well-tolerated, non-toxic and highly biocompatible.     

纳米纤维素/聚乳酸复合材料的降解性能

目的研究纳米纤维素/聚乳酸(NCC/PLA)复合薄膜在不同降解条件下的降解情况。方法在p H值为3,7,11的溶液及紫外光照射条件下,降解自制的复合薄膜,通过测失重率、扫描电子显微镜观察、X射线光电子能谱分析等手段,分析p H值、光照和NCC的添加与复合材料降解能力间的关系,研究其降解机理,并与纯PLA薄膜对比。结果 NCC/PLA复合薄膜在碱性条件下质量损失最快,酸性稍慢,中性更慢,紫外光照射下最慢,复合薄膜质量损失均比纯PLA薄膜多。在p H值为3和7的溶液及紫外光照射降解后,NCC/PLA复合薄膜氧碳原子数量的比值均比未降解时增大,分别提高了35.16%,36.66%,38.65%。结论 NCC的添加提高了NCC/PLA复合薄膜的降解性能,在不同降解过程中,薄膜表面C原子所占比例减少,相对地O原子所占比例增加,氧碳原子数量的比值增大。     

淀粉接枝共聚物在淀粉/聚乳酸共混体系中的作用

研究了淀粉／聚乳酸共混体系的相容性，考察了淀粉－聚醋酸乙烯酯和淀粉－聚乳酸接枝共聚物对淀粉／聚乳酸共混体系相容性的影响。发现上述两种接枝共聚物均可有效地增加淀粉与聚乳酸的相容性，从而提高共混体系的耐水性的力学性能。     

C/PLA复合材料的体外降解特性研究

对C／PLA复合材料的体外降解特性进行了研究。考察了该复合材料在降解过程中吸水率,质量损失和宏观力学性能的变化,并与PLA进行了对比。结果表明,与PLA相比,C／PLA复合材料的吸水率增加,质量损失下降,弯曲强度和剪切强度的下降速度减小。在体外降解过程中,C／PLA复合材料的界面发生降解,界面弱化是造成复合材料力学性能下降的主要因素。     

Hydrolytic degradation of PCL/PEO copolymers in alkaline media

PCL/PEO copolymers with different compositions were obtained from ring opening polymerization of -caprolactone in the presence of ethylene oxide and characterized by various analytical techniques. Data collected from DSC and X-ray diffractometry suggested that the copolymer chains possess a blocky structure, leading to both PCL and PEO-type crystalline structures. Hydrolytic degradation of these copolymers was carried out in a pH=10.6 carbonate buffer solution at 37 °C. Comparison was made with a PCL homopolymer and a PCL/PEG blend which had the same gross composition as one of the copolymers. The results showed that the presence of PEO sequences considerably enhanced the hydrophilicity of the copolymers as compared with PCL homopolymer. Nevertheless, the degradability of PCL chains was not enhanced due to the phase separation between the two components. These materials should be of great interest for biomedical uses such as matrices for sustained drug delivery because of the presence of both hydrophilic and hydrophobic microdomains. ©2000 Kluwer Academic Publishers     

Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 5: Hydrolytically degradable materials

Macroporous hydrogels based on 2-hydroxyethyl methacrylate, 2-ethoxyethyl methacrylate and N-(2-hydroxypropyl)methacrylamide, methacrylic acid and [2-(methacryloyloxy)ethyl]trimethylammonium chloride crosslinked with N,O-dimethacryloylhydroxylamine were prepared. Hydrogels were degraded in a buffer of pH 7.4. Completely water-soluble polymers were obtained over time periods ranging from 2 to 40 days. The process of degradation was followed gravimetrically and by optical and electron microscopy. In vivo biological tests with hydrogels based on copolymers of 2-ethoxyethyl methacrylate/N-(2-hydroxypropyl)methacrylamide were performed.     

Study of impregnation of poly(l-lactide-ran-ε-caprolactone) copolymers with useful compounds in supercritical carbon dioxide

Outstanding controlled release materials were developed using statistically random copolymers of l-lactide (l-LA) with ε-caprolactone (CL) using Sn(oct)₂ as a catalyst at 150 °C for 24 h without solvent. Preparation of novel controlled release materials was carried out using useful organic compounds with low boiling points and synthetic random copolymers composed of l-LA and CL as base materials under supercritical carbon dioxide (scCO₂). Low-boiling-point compounds such as d-limonene, hinokitiol, and trans-2-hexenal were used. In impregnation experiments using scCO₂, the amounts of low-boiling-point compounds increased with an increase in l-LA content. When enzymatic degradation of poly(l-LA-ran-CL) was performed using lipase PS, copolymers with higher CL contents degraded more rapidly than did copolymers with higher l-LA content. In contrast, enzymatic degradation of copolymers occurred to a higher degree with increased l-LA content in enzymatic degradation by proteinase K. In a controlled release experiment with poly(l-LA-ran-CL) (=73/27), after 400 h of degradation by proteinase K, the remaining weight of the copolymer pellet was 6% and the amount of d-limonene remaining in the pellet was 15%.     

PLA的酸性降解及其机理分析

目的研究PLA在酸性条件下降解及其机理。方法通过在酸性水溶液中降解不同时间,得到一系列不同相对分子质量的PLA,利用黏度法、凝胶色谱以及红外光谱对PLA的降解机理进行研究。结果 PLA的数均分子量随降解时间的增加逐渐减小,失重率和降解率逐渐升高,在降解23 d后,产物的数均分子量从4050降至2490,失重率从9.9%升至75.1%,降解率从98.3%提高至99.0%。降解过程中,PLA的相对分子质量分布系数基本保持不变,一直维持在1.25左右。结论在降解过程中,酯键的断裂是PLA初步降解的主要方式,H+浓度的升高有利于催化酯键的断裂,加剧PLA降解。     

碳纳米管/PLA复合材料制备及性能

采用溶液共混法制备纯化和酸化碳纳米管(CNTs)/PLA(聚乳酸)复合膜, 并对CNTs的分散性以及材料的结晶形态、 电性能和降解性能进行了研究。结果表明, 通过SEM观察到经过酸化处理的CNTs能较好地分散在PLA基体中; 在偏光显微镜下能观察到CNTs起到成核剂的作用, 明显细化了晶粒; 加入少量的酸化CNTs能够提高CNTs/PLA复合材料导电性, 体积电阻率下降了7个数量级; 同时, 酸化CNTs能够提高CNTs/PLA复合材料的降解性。     

碳纤维增强聚乳酸复合材料体外降解特性

制备了碳纤维增强聚乳酸(C/ PLA) 骨折内固定复合材料, 研究了体外降解过程中其力学性能的变化。结果表明: 在体外降解过程中, C/ PLA 复合材料的各项力学性能均有不同程度的下降, 但经过硝酸处理后的C/PLA 复合材料降解速度缓慢, 表明界面结合强度的提高对降解过程起抑制作用。      

Structure-property relationships in the case of the degradation of massive poly(α-hydroxy acids) in aqueous media

Degradation of two lactic-glycolic copolymers, namely PLA37.5GA25 (75%dl-lactide and 25% glycolide in the feed) and PLA75GA25 (75%l-lactide and 25% glycolide) was investigatedin vitro using aqueous media to model physiological conditions. Various techniques were used to monitor the effects due to hydrolytic degradation including weighing, SEC (size-exclusion chromatography), potentiometry, cryometry, enzymatic assay, X-ray scattering,¹H-nuclear magnetic resonance and differential scanning calorimetry. It was found that degradation proceeded faster in the centre than at the surface of standard parallelepipedic specimens. This feature had already been found for PLA50 (poly(dl-lactic acid)). The degradation rates of PLA37.5GA25 and PLA75GA25 were compared and it was found that intrinsically amorphous PLA75GA25 crystallized as degradation proceeded, in contrast to PLA37.5GA25. The crystallization of PLA75GA25 was related to the preferential degradation at glycolic units, which led tol-lactic-enriched fragments susceptible to crystallize. No major differences were observed between ageing in iso-osmolar saline and pH 7.4 phosphate buffer. In contrast, in the case of PLA37.5GA25, distilled water favoured surface-centre differentiation, probably because of osmotic exchange related to the absence of ionic strength.     

Characterization of thermoplastic polyurethane/polylactic acid (TPU/PLA) tissue engineering scaffolds fabricated by microcellular injection molding

Polylactic acid (PLA) and thermoplastic polyurethane (TPU) are two kinds of biocompatible and biodegradable polymers that can be used in biomedical applications. PLA has rigid mechanical properties while TPU possesses flexible mechanical properties. Blended TPU/PLA tissue engineering scaffolds at different ratios for tunable properties were fabricated via twin screw extrusion and microcellular injection molding techniques for the first time. Multiple test methods were used to characterize these materials. Fourier transform infrared spectroscopy (FTIR) confirmed the existence of the two components in the blends; differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) confirmed the immiscibility between the TPU and PLA. Scanning electron microscopy (SEM) images verified that, at the composition ratios studied, PLA was dispersed as spheres or islands inside the TPU matrix and that this phase morphology further influenced the scaffold's microstructure and surface roughness. The blends exhibited a large range of mechanical properties that covered several human tissue requirements. 3T3 fibroblast cell culture showed that the scaffolds supported cell proliferation and migration properly. Most importantly, this study demonstrated the feasibility of mass producing biocompatible PLA/TPU scaffolds with tunable microstructures, surface roughnesses, and mechanical properties that have the potential to be used as artificial scaffolds in multiple tissue engineering applications.     

The effect of salts and pH buffered solutions on the phase transition temperature and swelling of thermoresponsive pseudogels based on <Emphasis Type="Italic">N-</Emphasis>isopropylacrylamide

The temperature sensitive nature of poly(N-isopropylacrylamide) makes it an attractive candidate for controlled drug delivery devices. A series of temperature responsive poly (N-isopropylacrylamide)-polyvinyl pyrrolidinone random copolymers were produced by free radical polymerisation using 1-hydroxycyclohexylphenyketone as a UV-light sensitive initiator. The chemical structure of the xerogels was characterised by means of Fourier transform infrared spectroscopy (FTIR). The copolymers possess a lower critical solution temperature (LCST) in pure water, but the transition temperature may be affected by the addition of various cosolutes. The LCST of the pseudogels (physically crosslinked gels) was investigated in distilled water and a variety of salt and pH buffer solutions, using modulated differential scanning calorimetry (MDSC) and rheological analysis. The pH buffer solutions prepared mimic the variety of conditions encountered by drug delivery systems administered orally. The pH effects on the LCSTs of the temperature sensitive gels appear not obvious; while the salts used to prepare the pH buffer solutions have a more notable effect (‘salting out effect’) on the phase transition temperature. All swelling studies were carried out on the hydrogels at 37°C in distilled water, pH buffer 1.2 and pH buffer 6.8. The swelling/dissociation behaviour of the gels is found to be highly dependent on the pH buffer solution used, as the salts incorporated in preparing the pH buffer solutions lowers the phase transition of the copolymers to below the test temperature of 37°C, thus making them less soluble.     

苎麻纤维/聚乳酸复合材料在不同pH环境下的水解行为

以生物基树脂聚乳酸为基体,以植物纤维苎麻为补强剂,利用熔融共混法制备了苎麻纤维/聚乳酸(RF/PLA)复合材料,考查了RF/PLA复合材料在不同pH环境下的水解行为,并以力学性能测试、SEM、DSC和维卡软化温度检测为手段对其降解行为进行了评估。结果表明:RF/PLA复合材料在碱性(pH=12.0)环境中的降解比在酸性(pH=2.0)和中性(pH=7.0)环境中的更快,界面侵蚀空化是其性能劣化的主要原因。RF的加入提高了PLA的结晶度和维卡软化温度,同时也加快了PLA的降解速度,降解导致材料的力学强度下降。随着降解过程的加剧,RF/PLA复合材料的结晶度和维卡软化温度因材料内部产生缺陷而有所降低;而纯PLA树脂的结晶度却随碱液处理时间的延长而增加,但其维卡软化温度没有发生明显的变化。