軟性可變形硼酸官能基化聚胺酯奈米粒子作為動態交聯劑應用於水凝膠之3D生物列印

Abstract

添加奈米粒子可提升水凝膠的3D列印性，然而，軟性且可變形奈米粒子於水凝膠網絡中對3D列印影響仍未被深入探討。本研究合成兩種具硼酸官能基之聚胺酯奈米粒子（PUB與PUB'）作為動態奈米交聯劑以構建可3D生物列印的水凝膠，其中，PUB 的軟鏈段僅由poly(ε-caprolactone) (PCL) 組成，而PUB'則由PCL、poly(D,L-lactide)及poly(3-hydroxybutyrate)依0.7/0.2/0.1莫耳比例組成。透過小角度X光散射分析顯示，PUB奈米粒子呈現球形結構，PUB'則為偏橢球形結構。基於動態點擊交聯化學所製備poly(ethylene glycol)水凝膠中，PUB'-交聯水凝膠表現出更高之剪切模量與蠕變抗性，且經由160 μm小口徑噴頭列印時PUB'-交聯水凝膠展現出優異的堆疊性與線條解析度。由時間解析SAXS分析進一步揭示PUB'奈米粒子於凝膠化過程中會延展並穩定維持橢球形態，該現象使水凝膠內部形成高達38%奈米粒子體積分率進而提升其列印堆疊性；相對地，PUB奈米粒子則由球形結構轉為扁平狀結構導致水凝膠內部奈米粒子體積分率僅18%。此外，兩種水凝膠皆可維持高達約92%的內皮細胞活性。綜上所述，本研究揭示了聚胺酯-硼酸奈米交聯劑於凝膠化過程中的形貌轉變機制及其對內部奈米粒子體積分率高低與3D列印堆疊性的影響，並進一步說明了軟性奈米粒子形貌在動態自癒合水凝膠與3D列印墨水設計上的關鍵角色。

Addition of nanoparticles in a hydrogel can enhance its three-dimensional (3D) printability. However, the role of soft, deformable nanoparticles in the 3D printability of a hydrogel network has not been explored so far. In this study, two boronic acid-functionalized polyurethane nanoparticles PUB and PUB' are synthesized as soft dynamic nano-crosslinker to construct 3D bioprintable hydrogel. The soft segment of PUB consists of poly(ε-caprolactone) (PCL) solely while that of PUB' consists of PCL, poly(D,L-lactide), and poly(3-hydroxybutyrate) in 0.7/0.2/0.1 molar ratio. Coherent small-angle X-ray scattering (SAXS) reveals that PUB nanoparticles are nearly spherical while PUB' nanoparticles are ellipsoidal. PUB'-crosslinked poly(ethylene glycol) hydrogel based on dynamic click chemistry has greater shear modulus and creep resistance than PUB-crosslinked hydrogel. When printed through a small (160 μm) nozzle, PUB'-based hydrogel exhibits superior stackability and filament resolution. Time-resolved SAXS analysis unveils that PUB' nanoparticles elongate and maintain a stable ellipsoidal morphology in the network during gelation, contributing to higher packing density (particle volume fraction 38%) and 3D stackability of the hydrogel. Meanwhile, PUB nanoparticles transform from spherical to ellipsoidal and are eventually flattened, leading to low packing density (particle volume fraction 18%) of the hydrogel. Moreover, endothelial cells laden in both hydrogels show high vitality (~92%). The unique shape deformation phenomenon of the polyurethane-boronic acid nano-crosslinker during gelation and the resulted high-density packing in the dynamic network provide insights into the role of soft nanoparticle morphology in the stackability of a dynamic self-healing hydrogel and the role of particle packing in designing 3D hydrogel inks.