新型角膜支架材料的制备及生物相容性研究

首先合成了一种新型可降解的三乙烯基交联剂,并以偶氮二异丁氰(A IBN)为引发剂与乙烯基吡咯烷酮(NVP)通过自由基聚合制备了一种新型的交联NVP角膜支架材料。对材料的吸水率、接触角和降解性能进行了测定,通过体内埋植实验和细胞培养对材料进行了生物相容性评价。结果表明材料的吸水率达到104%,接触角为41,°降解速率较为恒定;体内埋植实验研究表明,3个月后,材料已大部分降解,材料内出现胶原和角膜基质细胞,周围组织无明显的炎症反应;细胞培养实验表明,角膜上皮细胞在材料上可以较好的生长,没有明显的细胞毒性,具有良好的生物相容性,这种合成的新型交联NVP角膜支架材料将在角膜组织工程中具有潜在的应用价值。     

戊二醛交联对壳聚糖／羟基磷灰石-庆大霉素缓释材料性能的影响CSCD

背景:交联是骨组织工程材料改性的一种常用方法,但目前仍缺乏交联剂对载药人工骨材料性能影响的相关研究与报道。目的:研究戊二醛交联对壳聚糖/羟基磷灰石-庆大霉素载药人工骨材料力学性能、降解性能及体外药物缓释行为的影响。方法:分别制备壳聚糖质量分数为10%,20%,30%的壳聚糖/羟基磷灰石-庆大霉素载药人工骨材料与戊二醛交联壳聚糖/羟基磷灰石-庆大霉素载药人工骨材料,检测各组材料的机械强度、吸水率、降解率及体外药物释放行为。结果与结论:壳聚糖含量为10%,20%,30%壳聚糖/羟基磷灰石-庆大霉素的抗压强度分别为(10.16±1.17),(28.40±0.64),(23.28±1.30)MPa,经戊二醛交联后材料的抗压强度分别增大至(36.30±1.20),(51.60±2.08),(36.90±3.22)MPa。壳聚糖含量为10%,20%,30%壳聚糖/羟基磷灰石-庆大霉素交联后的吸水率与降解率均低于交联前。在体外缓释的第1天,30%壳聚糖/羟基磷灰石-庆大霉素的药物释放量为42.2%,材料经戊二醛交联处理后药物释放量降至33.6%,在随后的9 d,交联壳聚糖/羟基磷灰石-庆大霉素的总释放量均低于壳聚糖/羟基磷灰石-庆大霉素。表明戊二醛交联赋予了材料更好的生物稳定性,减缓了材料降解速率,显著改善了药物突释现象。     

新型生物可降解交联N-乙烯基吡咯烷酮(NVP)材料的制备

用甘油和丙交酯在辛酸亚锡的催化下合成了可降解的三羟基中间体 ,在三乙胺存在的条件下 ,末端用丙烯酰氯进行功能化 ,合成了可降解的三乙烯基交联剂 ,并且对中间体和交联剂进行了FTIR ,1H—NMR ,GPC分析表征。这种交联剂与乙烯基吡咯烷酮 (NVP)用偶氮二异丁氰 (AIBN)为引发剂自由基引发聚合制备了组织工程支架材料 ,并且对材料的基本性能(吸水率和接触角 )进行了分析表征。     

戊二醛交联对壳聚糖/羟基磷灰石-庆大霉素缓释材料性能的影响

背景：交联是骨组织工程材料改性的一种常用方法,但目前仍缺乏交联剂对载药人工骨材料性能影响的相关研究与报道。 目的：研究戊二醛交联对壳聚糖/羟基磷灰石-庆大霉素载药人工骨材料力学性能、降解性能及体外药物缓释行为的影响。 方法：分别制备壳聚糖质量分数为10%,20%,30%的壳聚糖/羟基磷灰石-庆大霉素载药人工骨材料与戊二醛交联壳聚糖/羟基磷灰石-庆大霉素载药人工骨材料,检测各组材料的机械强度、吸水率、降解率及体外药物释放行为。 结果与结论：壳聚糖含量为10%,20%,30%壳聚糖/羟基磷灰石-庆大霉素的抗压强度分别为(10.16±1.17),(28.40±0.64),(23.28±1.30) MPa,经戊二醛交联后材料的抗压强度分别增大至(36.30±1.20),(51.60±2.08),(36.90±3.22) MPa。壳聚糖含量为10%,20%,30%壳聚糖/羟基磷灰石-庆大霉素交联后的吸水率与降解率均低于交联前。在体外缓释的第1天,30%壳聚糖/羟基磷灰石-庆大霉素的药物释放量为42.2%,材料经戊二醛交联处理后药物释放量降至33.6%,在随后的9 d,交联壳聚糖/羟基磷灰石-庆大霉素的总释放量均低于壳聚糖/羟基磷灰石-庆大霉素。表明戊二醛交联赋予了材料更好的生物稳定性,减缓了材料降解速率,显著改善了药物突释现象。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

新型生物可降解交联N—乙烯基吡咯烷酮（NVP）材料的制备

用甘油和丙交酯在辛酸亚锡的催化下合成了可降解的三羟基中间体，在三乙胺存在的条件下，末端用丙烯酰氯进行功能化，合成了可降解的三乙烯基交联剂，并且对中间体和交联剂进行了FTIR，^1H-NMR,GPC分析表征。这种交联剂与乙烯基吡咯烷酮（NVP）用偶氮二异丁氰（AIBN）为引发剂自由基引发聚合制备了组织工程支架材料，并且对材料的基本性能（吸水率和接触角）进行了分析表征。     

京尼平交联明胶特性随时间变化的研究

研究了京尼平交联明胶材料的交联度、细胞毒性、溶胀度、降解率等特性随交联时间的变化.用1%京尼平交联明胶,按交联时间分为7组:10 min组、30 min组、1 h组、2 h组、12 h组、24 h组、72 h组.结果显示京尼平可有效交联明胶,随着交联时间延长,交联度增加,溶胀度和降解率降低.交联10 min的材料,交联度低(26.7%),溶胀度高(265%),不到一周就完全降解,说明材料很不稳定,易降解;交联30min的材料,交联度(45.7%)、溶胀度(207%)、降解率与10 min材料比都有明显变化,4周未完全降解,8周完全降解,说明京尼平可以在30 min内显著改变明胶性能;30 min后的材料,随交联时间延长,交联度逐渐增加,溶胀度和降解率逐渐降低.交联72 h的材料,交联度73.1%,溶胀度153%,12周仅降解15.6%.MTT法测各组材料细胞增殖率在87.9%～105.4%之间,说明京尼平交联明胶材料细胞毒性均很低.     

交联对胶原降解速率的影响

目的:研究交联反应对胶原降解速率的影响.方法:以热交联(DHT)、1-乙基-3-(3-二甲基氨丙基)-碳化二亚胺(EDC)化学交联以及EDC/DHT交联三种方法对胶原海绵材料进行处理,并测定材料在处理前后的降解速率.结果:各种交联反应均不同程度地提高了胶原的生物稳定性,降低了胶原的降解速率.     

可生物降解PLA/PCL、PELA/PECL高分子共混体系的早期降解行为——相结构与降解性能的关系

本文以吸水率,GPC、SEM等考察了聚d,1—乳酸(PLA)/聚ε—己内酯(PCL)、聚d,1—乳酸—聚乙二醇(PEG)/聚ε—己内酯—聚乙二醇(PEG)可生物降解共混多相体系的体外降解行为,研究了PH值、共混组成及相容性对降解性能的影响,并就共混物形态结构与降解性能的关系作了讨论。PLA/PCL共混体系,随PLA含量增大,吸水性增强,降解速率加快。PLA/PCL(75/25)共混物表现出较PLA更高的吸水宰,经65天降解,分子量显著下降。由于聚乙二醇链段的亲水性和内增容作用,PELA/PECL(50/50)共混物的吸水率较PLA/PCL(50/50)共混物大为提高。     

氧化海藻酸钠交联改性脱细胞基质材料及其细胞相容性研究

运用高碘酸钠氧化法制备新型的生物交联剂—氧化海藻酸钠(ADA)并将之用于交联改性脱细胞基质材料,通过检测一些交联指标及交联后材料的性能特征来研究ADA交联改性脱细胞基质材料的特点。实验中采用了目前典型的两类交联剂(戊二醛(GA)和京尼平(GP))作为实验对照组。用三种交联剂处理血管组织15min～72h,测定交联过程中的交联指数,并对彻底交联后材料的力学性能以及细胞相容性进行研究。结果表明,ADA交联脱细胞基质材料的交联速率、交联程度不亚于GA,明显优于GP;交联后的材料也具有更适宜的力学性能;在细胞相容性方面,ADA交联的材料也具有明显优于GA、与GP相当的这样非常理想的效果。综上所述,ADA是一种具有很大发展前景的生物组织交联剂。     

新型胶原支架材料改性的研究

针对脱细胞真皮基质作为复合移植用真皮支架所存在的渗透性较差、降解速率慢、生物活性低等缺点,采用新工艺技术制备了天然三维网络结构的新型胶原支架材料,探讨交联、复合及其顺序和打孔对其理化性能的影响,并通过成纤维细胞培养试验研究其生物相容性.理化性能检测结果显示:复合提高交联试样的孔隙率和延长降解时间;交联明显提高试样的孔隙率和拉伸强度并延长其降解时间;先复合后交联可以提高孔隙率和降解时间;打孔可以明显提高材料的透水汽性和孔隙率.成纤维细胞培养试验表明:成纤维细胞能在改性支架材料上黏附、增殖.新型胶原支架经复合、交联、打孔改性后,其透水汽性明显提高,达到(3372±83)g/(m2·d);孔隙率显著提高,达(94.20±2.5)%;拉伸强度较好,为(10.65±0.32)MPa;体外降解时间为(38.3±1.0)h,通过适当改变交联剂的用量在比较宽的范围,可以满足不同支架材料降解速率的要求;细胞相容性良好.新型胶原支架经复合、交联、打孔改性后有望作为复合移植用的真皮支架.     

胶原蛋白海绵交联工艺的优化

背景：胶原蛋白材料具有良好的生物相容性和生物可降解性,但在临床应用过程中也暴露出了机械强度低、耐降解性能差等问题。大量研究报道,通过适当的交联可以改善胶原蛋白材料的缺陷,调控其多孔网络结构、溶胀性和降解性。 目的：优化胶原蛋白海绵的碳化二亚胺交联工艺,探讨其最佳工艺条件。 方法：利用碳化二亚胺对胶原蛋白海绵进行交联改性,得到具有疏松、多孔网络结构的胶原蛋白海绵,同时采用正交实验对交联工艺进行优化,单因素中选择碳化二亚胺浓度(5,10,20,30,40,50,60,70,80,90,100 mmol/L)、交联时间(2,4,6,8,12,16,20,24 h)及交联温度(5,10,15,20,25,30,35 ℃)为实验因子,以孔径、孔隙率、吸水性、降解率来筛选胶原蛋白海绵交联的最佳工艺。 结果与结论：当碳化二亚胺浓度为50 mmol/L、交联温度为20 ℃、交联时间为6 h时,胶原蛋白海绵的各项性能最为优越,为最优工艺条件,其中平均孔径大小为105 μm,孔隙率为79.45%,吸水率为287.14%,降解率最优为15.04%(2 d)。表明通过对胶原蛋白海绵的交联改性,极大提高了海绵的吸水性能和耐降解性能。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

Suppression of cell attachment and protein adsorption onto amphiphilic polylactide-grafted dextran films

To develop novel biodegradable biomedical materials, polylactide-grafted dextrans (Dex-g-PLA)s having various lengths, numbers of graft chains and sugar units were synthesized using the trimethylsilyl (TMS) protection method. To explore the possibility of using Dex-g-PLA as a biomedical soft-material, the contact angle, cell attachment and protein adsorption properties of the films prepared from these biodegradable and amphiphilic graft co-polymers were investigated. The poly-L-lactide (PLLA) film did not absorb water at all because of its high hydrophobicity, while the graft co-polymer films started immediately to swell after immersion in PBS. The percentage of water absorption at equilibrium increased with increasing sugar unit content. The receding contact angle of the Dex-g-PLA films against water was smaller than that of the PLLA film. The receding contact angle of Dex-g-PLA films against water decreased with increasing the sugar unit content. The top surface of the Dex-g-PLA film was suggested to be covered with hydrophilic Dex segments by means of annealing in water and to afford the wettable surface. Such a wettable surface led to the suppression of cell attachment and protein adsorption onto the film.     

Evaluation and biological characterization of bilayer gelatin/chondroitin-6-sulphate/hyaluronic acid membrane

A biodegradable polymer scaffold was developed using gelatin, chondroitin-6-sulphate, and hyaluronic acid in the form of bilayer network. The bilayer porous structure of gelatin-chondroitin-6-sulphate-hyaluronic acid (G-C6S-HA) membrane was fabricated using different freezing temperatures followed by lyophilization. 1-Ethyl-3(3-dimethylaminopropyl) carbodiimide was used as crosslinking agent to improve the biological stability of the scaffold. The morphology, physical-chemical properties, and biocompatibility of bilayer G-C6S-HA membrane were evaluated in this study. The functional groups change in crosslinked G-C6S-HA scaffold was characterized by fourier transform infrared spectroscopy. The retention of glycosaminoglycan contents and matrix degradation rate were also examined by p-dimethylamino benzaldehyde and 2,4,6-trinitrobenzene sulphonic acid, respectively. Water absorption capacity was carried out to study G-C6S-HA membrane water containing characteristics. The morphology of the bilayer G-C6S-HA membrane was investigated under scanning electron microscope and light microscopy. In vitro biocompatibility was conducted with MTT test, LDH assay, as well as histological analysis. The results showed that the morphology of bilayer G-C6S-HA membrane was well reserved. The physical-chemical properties were also adequate. With good biocompatibility, this bilayer G-C6S-HA membrane would be suitable as a matrix in the application of tissue engineering.     

Preparation and Properties of a Novel Biodegradable Polyester Elastomer with Functional Groups

A novel biodegradable poly(sebacate-glycerol-citrate) (PGSC) elastomer with functional groups was prepared in this study. First, moldable mixtures were obtained by mixing citric acid with the poly(glycerol-sebacate) (PGS) pre-polymers synthesized in our lab. The PGSC elastomers were obtained from moldable mixtures that were thermally cured in the moulds. Then, the structures, compositions and properties of the elastomers were studied by Fourier transformation infrared spectroscopy (FT-IR), swelling test, differential scanning calorimeter (DSC), tensile test, water contact angle measurement, water absorption experiments and a in vitro degradation test. It showed that the hydroxyl groups remained in the elastomers which would endow the polymer chains with functionality such as good surface modification. By controlling the thermal curing time, the compositions of the PGSC elastomers were adjusted for different mechanical and biodegradable properties. Therefore, PGSC elastomers might be used as anti-conglutination films in surgery, guided tissue regeneration membranes and drug-delivery matrices.     

Synthesis, characterization, and osteocompatibility evaluation of novel alanine-based polyphosphazenes

This study deals with the synthesis and in vitro osteocompatibility evaluation of two novel alanine-containing biodegradable ester polyphosphazenes as candidates to form self-setting composites with hydroxyapatite (HAp) precursors. The two novel biodegradable polyphosphazenes synthesized were poly[(ethyl alanato)1.0(ethyl oxybenzoate)1.0 phosphazene] (PN-EA/EOB) and poly[(ethyl alanato)1.0(propyl oxybenzoate)1.0 phosphazene] (PN-EA/POB). The polymers were characterized by multinuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), and gel permeation chromatography (GPC). Biodegradability and percentage water absorption of the polymers were evaluated by following the mass change in phosphate buffer (pH 7.4) at 37 degrees C. PN-EA/POB underwent faster degradation and showed higher water absorption compared to PN-EA/EOB. Both polymers became insoluble in common organic solvents following hydrolysis presumably due to crosslinking reactions accompanying the degradation process. Osteoblast cell adhesion and proliferation on PN-EA/EOB and PN-EA/POB was followed by scanning electron microscopy (SEM) and by using a biochemical assay. Both PN-EA/EOB and PN-EA/POB supported the adhesion and proliferation of primary rat osteoblast cells in vitro. Furthermore, the enzymatic activity of the osteoblast cells cultured on the polymers was confirmed by the alkaline phosphatase activity. Thus, these biodegradable amino-acid-based polyphosphazenes are promising new materials for forming self-setting bone cements.     

Novel micro-crosslinked poly(organophosphazenes) with improved mechanical properties and controllable degradation rate as potential biodegradable matrix

As biodegradable materials, linear polyphosphazenes undergo rapid hydrolysis degradation but exhibit poor mechanical properties. Blending with biodegradable polyesters or inorganic particles strengthen their mechanical properties but give rise to slower degradation rate. To balance the mechanical properties and the degradation rate, micro-crosslinked polyphosphazenes were synthesized in this study. Their glass transition temperatures, mechanical properties, and in vitro degradation behavior were investigated. 2-hydroxyethyl methacrylate (HEMA) was firstly attached to the side chain along with glycine ethyl ester to prepare co-substituted poly(organophosphazene) with pendant ethenyl substituents. The co-substituted poly(organophosphazene) was blended with HEMA or acrylic acid (AA) followed by a free radical polymerization to prepare micro-crosslinked poly(organophosphazenes). The resulting crosslinked polymers showed two separate glass transition temperatures depending on the HEMA or AA feed. Incorporation of crosslinking affected the mechanical properties positively. Crosslinked poly(organophosphazenes) showed an approximately 11-17 fold increase in terms of modulus of elasticity when compared to the linear counterpart. In vitro degradation tests indicated that HEMA-crosslinked polymers hydrolyzed at a retarded rate while AA-crosslinked polymers hydrolyzed at a moderate rate compared to linear polymers.     

Fabrication and characterization of hydrophilic electrospun membranes made from the block copolymer of poly(ethylene glycol-co-lactide)

To improve the hydrophilicity, pliability, and egradability of some biodegradable polymers such as polylactide (PLA), a triblock copolymer, and poly(ethylene glycol-co-lactide) (PELA) has been electrospun into fibrous membranes in the fiber sizes of 7.5 microm to 250 nm. The relationship between electrospinning parameters (such as voltage, concentration, and feeding rate) and the fiber diameters has been investigated. The characterizations for the structure and morphology of electrospun membranes were carried out using differential scanning calorimetry (DSC), (1)H NMR, and scanning electron microscopy (SEM). The hydrophilicity of the membrane was determined by contact angle measurements in bi-distilled water, and it was shown that the hydrophilicity of the copolymer could be adjusted by the content of the poly (ethylene glycol) (PEG) segment in the copolymer. The results of in vitro degradation study showed that the submicrostructure of the fibrous membrane and the incorporation of hydrophilic PEG into PLA block could accelerate the degradation of the membrane in regards to the changes of inherent viscosity, tensile strength, and weight loss.     

Genipin-crosslinked gelatin microspheres as a drug carrier for intramuscular administration: in vitro and in vivo studies

Gelatin microspheres have been widely evaluated as a drug carrier. Nevertheless, gelatin dissolves rather rapidly in aqueous environments, making the use of the polymer difficult for the production of long-term delivery systems. This adverse aspect requires the use of a crosslinking agent in forming nonsoluble networks in microspheres. However, the use of crosslinking agents such as formaldehyde and glutaraldehyde can lead to toxic side effects owing to residual crosslinkers. In an attempt to overcome this problem, a naturally occurring crosslinking agent (genipin) was used to crosslink gelatin microspheres as a biodegradable drug-delivery system for intramuscular administration. Glutaraldehyde was used as a control. In the in vitro study, the morphology, dynamic swelling, and antienzymatic degradation of test microspheres were evaluated. In the in vivo study, the biocompatibility and degradability of test microspheres were implanted in the skeletal muscle of a rat model via intramuscular injection. The results obtained in the study suggested that crosslinking of gelatin microspheres with glutaraldehyde or genipin may produce distinct crosslinking structures. The water transport mechanism in both the glutaraldehyde- and genipin-crosslinked gelatin microspheres exhibit anomalous behavior ranging from Fickian to Case-II extremes. The increase of the swelling diameter for the genipin-crosslinked microspheres was significantly less than that observed for the glutaraldehyde-crosslinked microspheres. In the animal study, it was found that the degree in inflammatory reaction for tissues implanted with the genipin-crosslinked microspheres was significantly less than that implanted with the glutaraldehyde-crosslinked microspheres. Additionally, the degradation rate of the genipin-crosslinked microspheres was significantly slower than their glutaraldehyde-crosslinked counterparts. These results indicated that the genipin-crosslinked gelatin microspheres may be used as a long-acting drug carrier for intramuscular administration.