以呋喃、咪唑官能基改質幾丁聚醣應用於光固化黏合劑

Abstract

現今技術在手術後重新連接、封合組織的方法多是用機械性固定的方法，如：手術縫線、手術釘、醫用鋼絲，而這種方式有諸多的缺點，首先都是侵入性的療法，破壞傷口周遭組織，使患者承受較大痛感，而且操作較為困難、耗時，且無法讓傷口達到完全密封，有細菌感染以及體液與空氣滲漏的問題。因此組織黏合材料，開始成為手術縫線、手術釘替代品。 而本研究希望可以做出控制固化時間的組織黏合材料：以幾丁聚醣為基底，使用EDC/NHS側練上引入呋喃、咪唑官能基，選擇甲烯藍為光敏劑，使用658nm的紅光二極體照射並起始幾丁聚醣的光交聯反應。改質後的幾丁聚醣利用核磁共振儀(NMR)、衰減式全反射傅立葉轉換紅外線光譜圖(ATR-IR)、紫外-可見光光譜(UV-VIS)進行結構分析，再以拉力測試、膨潤實驗測試其機械性質，最後檢測材料的細胞毒性。 實驗結果顯示，引入咪唑、呋喃官能基，確實讓幾丁聚醣有光交聯能力，可以利用光照控制起始交聯時間，且交聯後材料穩定性足夠，並在細胞毒性測試中是屬於生物可接受範圍，但是其強度稍弱，不適用於組織黏合材料，未來可以改用較低分子量與較高去乙醯度的的幾丁聚醣來改善此問題或可往其他應用，如再生醫學、傷口修復上使用，這種光起始的幾丁聚醣有其未來發展潛能。

Current technologies for reconnecting and sealing tissues after surgical procedures are most mechanical type fixed, such as sutures, wires, and staples. Those methods have several disadvantages. First, they are invasive procedures, create secondary damage surrounding tissue of wound, and let patients suffer more pain. More complicated processes make the use of those ways for wound closure is time consuming. It cannot seal wound absolutely, having the problem of infection, and do not stop body fluid and air leakages. Consequently, the novel tissue adhesion glue, surgical adhesive biomaterials, instead sutures, wires, and staples. We hope to make tissue adhesive agent that can control curing time, select chitosan as basic substrate, and utilize EDC/NHS reaction to introduce furan/imidazole functional groups, which are sensitive to radiation energy. Choose Methylene blue as photosensitizer, and use red laser diode (658nm, 100mW). The modified-chitosan is radiated by red laser and initiate photo-curable reaction. The modified-chitosan was analyzed by Nuclear Magnetic Resonance Spectroscopy (NMR), Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), and UV-vis absorbance Spectrum to confirm chemical structure, found its physical strength and stability by tension test and repeatable swelling test. Finally, We examined cytotoxicity of the modified-chitosan by MTT assay. The result showed that introducing furan/imidazole functional groups into chitosan actually made chitosan become photo-crosslinkable. We can exploit photo radiation to control the initial time of crosslink and acquire a stable linkage. Through the MTT assay, the result proved that the modified-chitosan is bio-acceptable. While, the tension test showed it has weak strength, which was not suitable for tissue adherence, it may be improved by using chitosan with lower molecular weights or higher degree of deacetylation ratio in the future or we can apply this material into different field, such as wound healing, tissue engineering. In conclusion, this photo-curable chitosan still has its potential for future development.