Chen Shixuan, Shi Junbin, Xu Xiaolin, Ding Jianyang, Zhong Wen, Zhang Lu, Xing Malcolm, Zhang Lin
Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Departments of Mechanical Engineering, Biochemistry and Medical Genetics, University of Manitoba, and Manitoba Institute of Child Health, Winnipeg, MB R3T 2N2, Canada.
Departments of Mechanical Engineering, Biochemistry and Medical Genetics, University of Manitoba, and Manitoba Institute of Child Health, Winnipeg, MB R3T 2N2, Canada.
Colloids Surf B Biointerfaces. 2016 Apr 1;140:574-582. doi: 10.1016/j.colsurfb.2015.08.041. Epub 2015 Aug 28.
The mechanical miss-match between the host and an implanted foreign body is one of the primary causes for implantation failure. To enhance the efficacy in wound repair, we developed stiffness-tunable temperature-sensitive hydrogels composed of poly(amidoamine) (PAA)-based poly(n-isopropyl acrylamide) (PNIPAM). PNIPAM-PAA hydrogels with three different stiffness fabricated by varying the concentrations of poly(amidoamine) were chosen for morphology and rheology tests. The degradation rate and cell compatibility of gels were also characterized. The PAA-PNIPAM hydrogels were then tested in a wound healing model of mice with full-thickness skin loss. We found that the stiffness of hydrogels has an impact on the wound healing process mainly by regulating the cell activities in the proliferation phase. PNIPAM-PAA hydrogels with appropriate stiffness reduce scar formation and improve wound healing by promoting myofibroblast transformation, keratinocytes proliferation, extracellular matrix synthesis and remodeling. Moreover, the stiffness of hydrogels impact on the secretion of TGF-β1 and bFGF, which play an important role in skin wound healing. These results suggest that the therapeutic effects of hydrogels in skin wound healing can by regulated by hydrogels' stiffness.
宿主与植入异物之间的机械不匹配是植入失败的主要原因之一。为提高伤口修复效果，我们研发了由基于聚（酰胺胺）（PAA）的聚（N-异丙基丙烯酰胺）（PNIPAM）组成的刚度可调温度敏感水凝胶。通过改变聚（酰胺胺）的浓度制备了三种不同刚度的PNIPAM-PAA水凝胶，用于形态学和流变学测试。还对凝胶的降解速率和细胞相容性进行了表征。然后在全层皮肤缺损的小鼠伤口愈合模型中测试了PAA-PNIPAM水凝胶。我们发现水凝胶的刚度主要通过调节增殖期的细胞活性来影响伤口愈合过程。具有适当刚度的PNIPAM-PAA水凝胶通过促进肌成纤维细胞转化、角质形成细胞增殖、细胞外基质合成和重塑，减少瘢痕形成并改善伤口愈合。此外，水凝胶的刚度影响TGF-β1和bFGF的分泌，这在皮肤伤口愈合中起重要作用。这些结果表明，水凝胶在皮肤伤口愈合中的治疗效果可通过水凝胶的刚度来调节。
