優化奈米-微米表面結構以增強成骨分化

Abstract

在骨缺損修復領域，雖然自體骨和異體骨移植被視為黃金標準療法，然而其應用範圍受限於組織來源的不足和供體部位的相關併發症。利用組織工程技術所開發的合成支架為極具潛力的替代方案，但有效整合植入物與骨組織界面仍是一項重要挑戰。過去研究指出，微米到奈米尺度的表面結構可促進成骨相關基因表現及提升界面穩定性，顯著強化骨與植入物整合。此外，毫米尺度的波浪狀結構亦證實能有效提升成骨分化能力。本研究透過電紡絲技術，製備具波浪結構之聚乳酸（PLLA）微米纖維支架，並結合奈米尺度沸石咪唑骨架-8（ZIF-8）顆粒，以優化支架的奈米與微米尺度結構。結果顯示，載有較大的ZIF-8奈米顆粒的支架，顯著促進人類骨髓間質幹細胞（MSCs）的成骨基因表現與礦化能力。此外支架的波浪狀纖維結構更進一步放大此成骨效果。控制實驗則進一步證明，此成骨效果主要來自ZIF-8顆粒誘導的奈米特徵，而非鋅離子的單純釋放。因此，本研究所提出的多尺度奈米／微米表面結構策略，在臨床上具備顯著潛力，有望大幅改善植入物與骨組織的界面整合效果。

Bone autografting and allografting, considered the clinical gold standard for bone defect repair, are limited by insufficient tissue availability and donor site morbidity. Tissue-engineered grafts offer promising alternatives, yet achieving effective integration at the implant-bone interface remains a significant challenge. Previous studies have demonstrated that micro- to nanoscale surface topographies critically enhance bone-implant integration by promoting osteogenic gene expression and mechanical stability at the interface. Moreover, millimeter-scale wavy structures have been demonstrated to enhance osteogenic differentiation. In this study, electrospun poly(lactic acid) (PLLA) microfibrous scaffolds were developed and integrated with nanoscale zeolitic imidazolate framework-8 (ZIF-8) nanoparticles to optimize nano and microscale topographical cues. Our results indicate that ethanol treatment facilitated the formation of larger ZIF-8 nanoparticles on scaffold surfaces, significantly enhancing osteogenic gene expression and mineralization of human mesenchymal stem cells (MSCs). Additionally, the introduction of microscale wavy fiber structures further amplified these osteogenic effects. Control experiments confirmed that the enhanced osteogenic differentiation primarily resulted from the nanotopographical cues provided by ZIF-8 nanoparticles rather than Zn2+ release alone. This multiscale nano/microstructural strategy thus presents significant clinical potential to substantially improve implant-bone interface integration.