化學交聯水膠包覆人類血小板裂解液於促進血管新生之探討

Abstract

近年來，周邊性動脈阻塞性疾病的患者逐漸增加，但目前臨床上對於此疾病患者的治療方式大多以支架、氣球將阻塞的動脈撐開或進行血管繞道手術，病情較嚴重的患者更可能面臨到截肢的選擇。為了促進周邊性組織的血液循環，本研究將生醫材料製作成水膠的形式，使用乙二醛將甲殼素與明膠相互交聯進而包覆血小板裂解液，期望能於周邊性組織緩慢釋放生長因子並促進血管新生。為了要鑑定此系統釋放包覆物的釋放機制，本研究包覆不同分子量大小的螢光異硫氰酸鹽右旋醣酐及血小板裂解液進行分析，另一方面，於細胞實驗中我們發現血小板裂解液不僅能夠促進人類臍動脈內皮細胞和纖維母細胞細胞株(HS68)的移動，亦能使人類臍動脈內皮細胞形成管柱。此外，在受精卵及仿真皮膚系統中，我們發現血小板裂解液結合生醫材料於促進血管新生方面具有相當大的潛能，未來值得繼續研究。

More and more people suffered from peripheral artery disease (PAD) due to insufficient blood supply to the legs. Currently, the standard therapy for improving blood flow to the affected extremity is either surgical or endovascular revascularization. However, their therapeutic effects are sometimes limited and still many people with PAD may require amputation. The purpose of our research is to combine biomaterials with human platelet lysate (HPL) to increase the blood flow in the ischemia area. In our study, we developed a chitosan-gelatin hydrogel crosslinked by glyoxal for sustained release HPL. To investigate the release profile of this hydrogel system, we used hydrogel to incorporate the FITC-dextran with different molecular weight and the release pattern were determined. On the other hand, the angiogenic effect of HPL was studied in the tube formation assay and transwell migration assay of human umbilical vein endothelial cells (HUVEC). Moreover, supplementing culture medium with HPL induced the migration of HS68 cells in an in vitro wound healing assay suggesting the potential of HPL to facilitate wound closure. Chick chorioallantoic membrane (CAM) assay revealed that HPL can stimulate angiogenesis in vivo. Given the results of in vitro and in vivo experiments, we conclude that the hydrogel-based system of HPL has great potential to increase the blood flow for the treatment of ischemic wounds.