Ghanaati Shahram, Webber Matthew J, Unger Ronald E, Orth Carina, Hulvat James F, Kiehna Sarah E, Barbeck Mike, Rasic Angela, Stupp Samuel I, Kirkpatrick C James
Institute of Pathology, Langenbeckstr. 1, Johannes Gutenberg University, 55101 Mainz, Germany.
Biomaterials. 2009 Oct;30(31):6202-12. doi: 10.1016/j.biomaterials.2009.07.063. Epub 2009 Aug 15.
Biomaterials that promote angiogenesis have great potential in regenerative medicine for rapid revascularization of damaged tissue, survival of transplanted cells, and healing of chronic wounds. Supramolecular nanofibers formed by self-assembly of a heparin-binding peptide amphiphile and heparan sulfate-like glycosaminoglycans were evaluated here using a dorsal skinfold chamber model to dynamically monitor the interaction between the nanofiber gel and the microcirculation, representing a novel application of this model. We paired this model with a conventional subcutaneous implantation model for static histological assessment of the interactions between the gel and host tissue. In the static analysis, the heparan sulfate-containing nanofiber gels were found to persist in the tissue for up to 30 days and revealed excellent biocompatibility. Strikingly, as the nanofiber gel biodegraded, we observed the formation of a de novo vascularized connective tissue. In the dynamic experiments using the dorsal skinfold chamber, the material again demonstrated good biocompatibility, with minimal dilation of the microcirculation and only a few adherent leukocytes, monitored through intravital fluorescence microscopy. The new application of the dorsal skinfold model corroborated our findings from the traditional static histology, demonstrating the potential use of this technique to dynamically evaluate the biocompatibility of materials. The observed biocompatibility and development of new vascularized tissue using both techniques demonstrates the potential of these angiogenesis-promoting materials for a host of regenerative strategies.
促进血管生成的生物材料在再生医学中具有巨大潜力，可实现受损组织的快速血管重建、移植细胞的存活以及慢性伤口的愈合。本文使用背侧皮褶腔室模型评估了由肝素结合肽两亲物和硫酸乙酰肝素样糖胺聚糖自组装形成的超分子纳米纤维，以动态监测纳米纤维凝胶与微循环之间的相互作用，这代表了该模型的一种新应用。我们将该模型与传统的皮下植入模型相结合，用于对凝胶与宿主组织之间的相互作用进行静态组织学评估。在静态分析中，发现含硫酸乙酰肝素的纳米纤维凝胶在组织中可保留长达30天，并显示出优异的生物相容性。引人注目的是，随着纳米纤维凝胶的生物降解，我们观察到了新生血管化结缔组织的形成。在使用背侧皮褶腔室的动态实验中，通过活体荧光显微镜监测，该材料再次表现出良好的生物相容性，微循环扩张最小，仅有少量黏附的白细胞。背侧皮褶模型的新应用证实了我们从传统静态组织学中获得的发现，证明了该技术在动态评估材料生物相容性方面的潜在用途。使用这两种技术观察到的生物相容性以及新血管化组织的形成，证明了这些促进血管生成材料在一系列再生策略中的潜力。
