Li Bing, Davidson Jeffrey M, Guelcher Scott A
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN 3723, USA.
Biomaterials. 2009 Jul;30(20):3486-94. doi: 10.1016/j.biomaterials.2009.03.008. Epub 2009 Mar 28.
A key tenet of tissue engineering is the principle that the scaffold can perform the dual roles of biomechanical and biochemical support through presentation of the appropriate mediators to surrounding tissue. While growth factors have been incorporated into scaffolds to achieve sustained release, there are a limited number of studies investigating release of biologically active molecules from reactive two-component polymers, which have potential application as injectable delivery systems. In this study, we report the sustained release of platelet-derived growth factor (PDGF) from a reactive two-component polyurethane. The release of PDGF was bi-phasic, characterized by an initial burst followed by a period of sustained release for up to 21 days. Despite the potential for amine and hydroxyl groups in the protein to react with the isocyanate groups in the reactive polyurethane, the in vitro bioactivity of the released PDGF was largely preserved when added as a lyophilized powder. PUR/PDGF scaffolds implanted in rat skin excisional wounds accelerated wound healing relative to the blank PUR control, resulting in almost complete healing with reepithelization at day 14. The presence of PDGF attracted both fibroblasts and mononuclear cells, significantly accelerating degradation of the polymer and enhancing formation of new granulation tissue as early as day 3. The ability of reactive two-component PUR scaffolds to promote new tissue formation in vivo through local delivery of PDGF may present compelling opportunities for the development of novel injectable therapeutics.
组织工程学的一个关键原则是,支架能够通过向周围组织呈现适当的介质来发挥生物力学和生化支持的双重作用。虽然生长因子已被纳入支架以实现持续释放,但研究从具有潜在用作可注射递送系统的反应性双组分聚合物中释放生物活性分子的研究数量有限。在本研究中,我们报道了血小板衍生生长因子(PDGF)从一种反应性双组分聚氨酯中的持续释放。PDGF的释放是双相的,其特征是初始爆发,随后是长达21天的持续释放期。尽管蛋白质中的胺基和羟基有可能与反应性聚氨酯中的异氰酸酯基发生反应,但当以冻干粉末形式添加时,释放的PDGF的体外生物活性在很大程度上得以保留。植入大鼠皮肤切除伤口的PUR/PDGF支架相对于空白PUR对照加速了伤口愈合,在第14天实现了几乎完全愈合并重新上皮化。PDGF的存在吸引了成纤维细胞和单核细胞,早在第3天就显著加速了聚合物的降解并增强了新肉芽组织的形成。反应性双组分PUR支架通过局部递送PDGF促进体内新组织形成的能力可能为新型可注射治疗剂的开发提供引人注目的机会。