【 文献重点摘要 】
 

Particle size, stiffness and surface functionality are important in determining the injection site, safety and efficacy of injectable soft-tissue fillers. Methods to produce soft injectable biomaterials with controlled particle characteristics are therefore desirable. Here we report a method based on suspension photopolymerization and semi-interpenetrating network (semi-IPN) to synthesize soft, functionalizable, spherical hydrogel microparticles (MP) of independently tunable size and stiffness. MP were prepared using acrylated forms of polyethylene glycol (PEG), gelatin and hyaluronic acid. Semi-IPN MP of PEG-diacrylate and PEG were used to study the effect of process parameters on particle characteristics. The process parameters were systematically varied to produce MP with size ranging from 115 to 515 μm and stiffness ranging from 190 to 1600 Pa. In vitro studies showed that the MP thus prepared were cytocompatible. The ratio and identity of the polymers used to make the semi-IPN MP were varied to control their stiffness and to introduce amine groups for potential functionalization. Slow-release polymeric particles loaded with Rhodamine or dexamethasone were incorporated in the MP as a proof-of-principle of drug incorporation and release from the MP. This work has implications in preparing injectable biomaterials of natural or synthetic polymers for applications as soft-tissue fillers.

Keywords

Soft-tissue filler; Hydrogel; Microparticles; Suspension photopolymerization

颗粒大小、硬度和表面功能是决定可注射软组织填充物注射部位、安全性和有效性的重要因素。因此，制备具有受控颗粒特性的软注射生物材料的方法是可取的。本文报道了一种基于悬浮光聚合和半互穿网络(Semi-IPN)合成尺寸和硬度独立可调的软的、可功能化的球形水凝胶微粒(MP)的方法。采用聚乙二醇(PEG)、明胶和透明质酸的丙烯酸酯形式制备MP。采用半互穿网络聚乙二醇(PEG)-双丙烯酸酯共聚物(MP)和聚乙二醇(PEG)研究了工艺参数对颗粒特性的影响。系统地改变工艺参数，制得粒度为115~515μm、刚度为190~1600Pa的MP。体外实验表明，所制备的微球具有细胞相容性。用来制备半IPN MP的聚合物的比例和特性是不同的，以控制它们的刚性，并引入胺基进行潜在的官能化。将载有罗丹明或地塞米松的缓释聚合物颗粒加入到MP中，作为药物从MP并入和释放的原则证明。这项工作对制备天然或合成聚合物的可注射生物材料作为软组织填充物具有重要意义。

关键词

软组织填充剂；水凝胶；微粒；悬浮光聚合