本文選題：肝素明膠偶聯(lián)物　切入點：氧化聚古洛糖醛酸　出處：《天津大學》2012年碩士論文　論文類型：學位論文

【摘要】：應用仿細胞外基質(ECM)思路設計的水凝膠,負載外源性生長因子后可直接作用于缺血性患處,在體內(nèi)降解過程中不斷釋放出生長因子而刺激細胞增殖、血管形成以及組織修復,從而實現(xiàn)治療性血管的形成。本文制備了肝素明膠偶聯(lián)物(HGC),并采用氧化聚古洛糖醛酸(PAG)水凝膠作為仿ECM載體,探討了HGC保護的堿性成纖維細胞生長因子(bFGF)從水凝膠中的釋放行為,并通過雞胚絨毛尿囊膜(CAM)模型和大鼠背部皮下氣囊模型評價了其血管化性能。 通過酸性水解法用海藻酸鈉制備了聚古洛糖醛酸(PG),而后以低溫高碘酸鈉氧化法制備出PAG。通過酰胺化反應向明膠引入了外源性氨基,從而提高了其反應活性。將肝素偶聯(lián)到明膠側鏈上,形成了結構類似于蛋白聚糖的HGC,而后將結合有bFGF的HGC、PAG以及氨基化明膠共交聯(lián)形成了PAG水凝膠。結果顯示,與海藻酸鹽水凝膠相比,PAG水凝膠的降解速率明顯減緩;肝素/bFGF重量比為2000時即可保證bFGF物理固定于PAG水凝膠網(wǎng)絡中,并使其緩慢釋放,證實HGC成分的加入對PAG水凝膠體系作為生長因子載體的重要性。 CAM模型結果顯示,PAG水凝膠體系中HGC和bFGF的加入量對CAM血管形成有著顯著的影響。0.5% HGC的加入量可以有效地保留bFGF的生物活性,從而促進新生血管的形成。bFGF和內(nèi)皮細胞生長因子(VEGF)的協(xié)同作用對CAM血管形成有著明顯的促進作用。大鼠背部皮下氣囊模型結果顯示,PAG水凝膠體系中HGC和bFGF的加入量對血管形成同樣有著重要的影響,1% HGC的加入量可以有效地促進新生血管的形成,而水凝膠中的bFGF濃度達到100 ng/mL后,再繼續(xù)增加bFGF濃度時所形成的血管密度反而降低。
[Abstract]:The hydrogels designed with ECM mimic extracellular matrix can directly act on ischemic affected areas after loading exogenous growth factors, and release growth factors to stimulate cell proliferation, angiogenesis and tissue repair during degradation in vivo. In this paper, the heparin gelatin conjugate HGCX was prepared, and the oxidized polyuronic acid hydrogel was used as the imitating ECM carrier. The release behavior of basic fibroblast growth factor (bFGF) protected by HGC from hydrogels was investigated. The vascularization properties were evaluated by chicken embryo chorioallantoic membrane (chorioallantoic) model and rat dorsal subcutaneous balloon model. Polyglumuronic acid (PGN) was prepared by acid hydrolysis with sodium alginate, and then PAG was prepared by oxidation of sodium periodate at low temperature. Exogenous amino groups were introduced into gelatin by amidation reaction. By coupling heparin to the side chain of gelatin, HGCs with similar structure to proteoglycan were formed, and then PAG hydrogels were co-crosslinked with bFGF and amino gelatin. When the weight ratio of heparin / bFGF is 2000, the bFGF can be physically immobilized in the PAG hydrogel network and released slowly. The importance of the addition of HGC to the PAG hydrogel system as a growth factor carrier was confirmed. The results of CAM model showed that the addition of HGC and bFGF in PAG hydrogel system had a significant effect on CAM angiogenesis. The addition of 0.5% HGC could effectively preserve the biological activity of bFGF. Therefore, the synergistic effect of bFGF and endothelial growth factor (VEGF) on CAM angiogenesis was found. The results of rat dorsal subcutaneous balloon model showed that HGC and bFGF were added into PAG hydrogel system. The addition of 1% HGC can effectively promote angiogenesis. However, when the concentration of bFGF in the hydrogel reached 100 ng/mL, the vascular density decreased when the concentration of bFGF continued to increase.
【學位授予單位】：天津大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R318.0

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