Baptista Marissa, Joukhdar Habib, Alcala-Orozco Cesar R, Lau Kieran, Jiang Shouyuan, Cui Xiaolin, He Steven, Tang Fengying, Heu Celine, Woodfield Tim B F, Lim Khoon S, Rnjak-Kovacina Jelena
Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, Australia.
Biomater Sci. 2020 Dec 15;8(24):7093-7105. doi: 10.1039/d0bm01010c.
The biophysical properties of biomaterials are key to directing the biological responses and biomaterial integration and function in in situ tissue engineering approaches. We present silk photo-lyogels, a biomaterial format fabricated using a new combinatorial approach involving photo-initiated crosslinking of silk fibroin via di-tyrosine bonds followed by lyophilization to generate 3D, porous lyogels showing physical properties distinct to those of lyophilized silk sponges or silk hydrogels. This fabrication approach allowed introduction of microchannels into 3D constructs via biofabrication approaches involving silk crosslinking around an array of 3D printed photocurable resin pillars to generate parallel channels or around a 3D printed sacrificial thermosensitive gel to generate interconnected channels in a rapid manner and without the need for chemical modification of silk fibroin. The presence of interconnected microchannels significantly improved migration of endothelial cells into 3D photo-lyogels in vitro, and tissue infiltration, photo-lyogel integration, and vascularization when implanted in vivo in a mouse subcutaneous model. Taken together, these findings demonstrate the feasibility and utility of a new combinatorial fabrication approach for generation of silk biomaterials that support cell interactions and implant integration for in situ tissue engineering approaches.
生物材料的生物物理特性是指导原位组织工程方法中生物反应、生物材料整合及功能的关键。我们展示了丝光致冻干凝胶，这是一种生物材料形式，采用一种新的组合方法制造，该方法涉及通过二酪氨酸键对丝素蛋白进行光引发交联，随后进行冻干，以生成三维多孔冻干凝胶，其物理特性与冻干丝海绵或丝水凝胶不同。这种制造方法允许通过生物制造方法将微通道引入三维构建体，该方法包括围绕一系列三维打印的光固化树脂柱对丝进行交联以生成平行通道，或围绕三维打印的牺牲热敏凝胶对丝进行交联以快速生成相互连接的通道，且无需对丝素蛋白进行化学修饰。相互连接的微通道的存在显著改善了体外内皮细胞向三维光致冻干凝胶的迁移，以及在小鼠皮下模型中体内植入时的组织浸润、光致冻干凝胶整合和血管化。综上所述，这些发现证明了一种新的组合制造方法用于生成支持原位组织工程方法中细胞相互作用和植入整合的丝生物材料的可行性和实用性。
