生物可降解聚胺酯奈米粒子交聯殼聚醣之自癒合水凝膠與冷凍凝膠

Abstract

水凝膠由於其高保水性和柔軟特性而廣泛用於組織工程中。開發具有可調節降解速率，適當環境響應性和可注射性的水凝膠仍然是一個挑戰。在這項研究中，可生物降解的雙官能聚氨酯（DFPU）奈米粒子分散體是由一種涉及使用乙二醛的水性製程合成的。這種DFPU 用於交聯乙二醇殼聚醣（CS）。在室溫下DFPU 和CS鍵結形成席夫鹼，成功製備出自癒合水凝膠。此外，在-20 ℃冷凍後產生冷凍凝膠。由於席夫鹼的性質，發現這些凝膠對pH 值和含胺分子敏感。此外，降解速率可以通過合成DFPU 之寡聚二醇類型進行調整。經由流變學測試證實了優異的自癒性能（損傷後恢復約100％）。自癒合凝膠和冷凍凝膠均可注射（分別通過26 號針和18 號針），並顯示出良好的細胞增殖。14 天大鼠植入顯示冷凍凝膠的低免疫應答。功能化的可生物降解聚胺酯奈米粒子為一交聯劑的新平台，可與含胺基生物大分子（例如殼聚醣）進行動態席夫反應，其有潛力產生應用於生物醫學的各種自癒合水凝膠和冷凍凝膠。

Hydrogels are widely used in tissue engineering owing to their high water retention and soft characteristics. It remains a challenge to develop hydrogels with tunable degradation rates, proper environmental responsiveness, and injectability. In this study, biodegradable difunctional polyurethane (DFPU) nanoparticle dispersions were synthesized from an eco-friendly waterborne process involving the use of glyoxal. Such DFPU was used to crosslink chitosan (CS). The Schiff base linkage between DFPU and CS successfully produced self-healing hydrogels at room temperature. Moreover, cryogels were generated after being frozen at -20 °C. These gels were found to be sensitive to pH values and amine-containing molecules owing to the property of Schiff bases. Besides, the degradation rates could be adjusted by the types of the component oligodiols in DFPU. Rheological evaluation verified the excellent self-healing properties (~100% recovery after damage). Both the self-healing gels and cryogels were injectable (through 26-gauge and 18-gauge needles, respectively) and demonstrated good cell proliferation. Rat implantation at 14 days showed low immune responses of cryogels. The functionalized biodegradable polyurethane nanoparticles represent a new platform of crosslinkers for biomacromolecules such as chitosan through dynamic Schiff reaction that may give rise to a wide varieties of self-healing gels and cryogels for biomedical applications.