Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Pharm Res. 2011 Jun;28(6):1282-93. doi: 10.1007/s11095-011-0391-z. Epub 2011 Feb 23.
Biodegradable elastomers, which can possess favorable mechanical properties and degradation rates for soft tissue engineering applications, are more recently being explored as depots for biomolecule delivery. The objective of this study was to synthesize and process biodegradable, elastomeric poly(ester urethane)urea (PEUU) scaffolds and to characterize their ability to incorporate and release bioactive insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF).
Porous PEUU scaffolds made from either 5 or 8 wt% PEUU were prepared with direct growth-factor incorporation. Long-term in vitro IGF-1 release kinetics were investigated in saline or saline with 100 units/ml lipase to simulate in vivo degradation. Cellular assays were used to confirm released IGF-1 and HGF bioactivity.
IGF-1 release into saline occurred in a complex multi-phasic manner for up to 440 days. Scaffolds generated from 5 wt% PEUU delivered protein faster than 8 wt% scaffolds. Lipase-accelerated scaffold degradation led to delivery of >90% protein over 9 weeks for both polymer concentrations. IGF-1 and HGF bioactivity in the first 3 weeks was confirmed.
The capacity of a biodegradable elastomeric scaffold to provide long-term growth-factor delivery was demonstrated. Such a system might provide functional benefit in cardiovascular and other soft tissue engineering applications.
可生物降解的弹性体具有用于软组织工程应用的有利机械性能和降解速率，最近作为生物分子递药的储库得到了更多的探索。本研究的目的是合成和加工可生物降解的弹性体聚（酯-氨酯）脲（PEUU）支架，并表征其包封和释放生物活性胰岛素样生长因子-1（IGF-1）和肝细胞生长因子（HGF）的能力。
通过直接生长因子掺入制备由 5 或 8wt%PEUU 制成的多孔 PEUU 支架。在盐水中或模拟体内降解的含 100 单位/ml 脂肪酶的盐水中研究了长期 IGF-1 释放动力学。细胞测定用于确认释放的 IGF-1 和 HGF 的生物活性。
IGF-1 释放到盐水中的过程在长达 440 天内呈现复杂的多相方式。5wt%PEUU 生成的支架比 8wt%支架更快地输送蛋白质。对于两种聚合物浓度，脂肪酶加速的支架降解在 9 周内导致超过 90%的蛋白质释放。在最初的 3 周内证实了 IGF-1 和 HGF 的生物活性。
证明了可生物降解弹性体支架提供长期生长因子输送的能力。这样的系统可能在心血管和其他软组织工程应用中提供功能益处。
