Patel Parul Natvar, Gobin Andrea S, West Jennifer L, Patrick Charles W
Department of Chemical Engineering, Rice University, Houston, Texas, USA.
Tissue Eng. 2005 Sep-Oct;11(9-10):1498-505. doi: 10.1089/ten.2005.11.1498.
The ultimate goal of this research is to develop an injectable cell-scaffold system capable of permitting adipogenesis to abrogate soft tissue deficiencies resulting from trauma, tumor resection, and congenital abnormalities. The present work compares the efficacy of photopolymerizable poly(ethylene glycol) and specific derivatives as a scaffold for preadipocyte (adipocyte precursor cell) viability, adhesion, and proliferation. Four variations of a poly(ethylene glycol) scaffold are prepared and examined. The first scaffold consists of poly(ethylene glycol) diacrylate, which is not susceptible to hydrolysis or enzymatic degradation. Preadipocyte death is observed over 1 week in this hydrogel configuration. Adhesion sites, specifically the laminin-binding peptide sequence YIGSR, were incorporated into the second scaffold to promote cellular adhesion as a prerequisite for preadipocyte proliferation. Preadipocytes remain viable in this scaffold system, but do not proliferate in this nondegradable hydrogel. The third scaffold system studied consists of poly(ethylene glycol) modified with the peptide sequence LGPA to permit polymer degradation by cell-secreted collagenase. No adhesion peptide is incorporated into this scaffold system. Cellular proliferation is initially observed, followed by cell death. The previous three scaffold configurations do not permit preadipocyte adhesion and proliferation. In contrast, the fourth system studied, poly(ethylene glycol) modified to incorporate both LGPA and YIGSR, permits preadipocyte adherence and proliferation subsequent to polymer degradation. Our results indicate that a scaffold system containing specific degradation sites and cell adhesion ligands permits cells to adhere and proliferate, thus providing a potential cell-scaffold system for adipogenesis.
本研究的最终目标是开发一种可注射的细胞支架系统，该系统能够促进脂肪生成，以消除因创伤、肿瘤切除和先天性异常导致的软组织缺陷。目前的工作比较了可光聚合的聚乙二醇及其特定衍生物作为前脂肪细胞（脂肪细胞前体细胞）活力、黏附及增殖支架的效果。制备并检测了聚乙二醇支架的四种变体。第一种支架由聚乙二醇二丙烯酸酯组成，它不易水解或被酶降解。在这种水凝胶结构中，观察到前脂肪细胞在1周内死亡。黏附位点，特别是层粘连蛋白结合肽序列YIGSR，被纳入第二种支架，以促进细胞黏附，这是前脂肪细胞增殖的先决条件。前脂肪细胞在该支架系统中保持存活，但在这种不可降解的水凝胶中不增殖。研究的第三种支架系统由用肽序列LGPA修饰的聚乙二醇组成，以允许聚合物被细胞分泌的胶原酶降解。该支架系统未纳入黏附肽。最初观察到细胞增殖，随后细胞死亡。前三种支架结构均不允许前脂肪细胞黏附与增殖。相比之下，研究的第四种系统，即同时掺入LGPA和YIGSR的聚乙二醇，在聚合物降解后允许前脂肪细胞黏附与增殖。我们的结果表明，含有特定降解位点和细胞黏附配体的支架系统能使细胞黏附与增殖，从而为脂肪生成提供了一种潜在的细胞支架系统。
