i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135, Portugal; INEB - Instituto Nacional de Engenharia Biomédica, Universidade do Porto, 4200-135, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-343, Portugal; CDRSP - Centre for Rapid and Sustainable Product Development, Polytechnic Institute of Leiria, 2430-028, Portugal.
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135, Portugal; INEB - Instituto Nacional de Engenharia Biomédica, Universidade do Porto, 4200-135, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-343, Portugal.
Acta Biomater. 2018 Jan 15;66:282-293. doi: 10.1016/j.actbio.2017.11.016. Epub 2017 Nov 8.
Cell-instructive hydrogels are attractive for skin repair and regeneration, serving as interactive matrices to promote cell adhesion, cell-driven remodeling and de novo deposition of extracellular matrix components. This paper describes the synthesis and photocrosslinking of cell-instructive pectin hydrogels using cell-degradable peptide crosslinkers and integrin-specific adhesive ligands. Protease-degradable hydrogels obtained by photoinitiated thiol-norbornene click chemistry are rapidly formed in the presence of dermal fibroblasts, exhibit tunable properties and are capable of modulating the behavior of embedded cells, including the cell spreading, hydrogel contraction and secretion of matrix metalloproteases. Keratinocytes seeded on top of fibroblast-loaded hydrogels are able to adhere and form a compact and dense layer of epidermis, mimicking the architecture of the native skin. Thiol-ene photocrosslinkable pectin hydrogels support the in vitro formation of full-thickness skin and are thus a highly promising platform for skin tissue engineering applications, including wound healing and in vitro testing models.
Photopolymerizable hydrogels are attractive for skin applications due to their unique spatiotemporal control over the hydrogel formation. This study reports the design of a promising photo-clickable pectin hydrogel which biophysical and biochemical properties can be independently tailored to control cell behavior. A fast method for the norbornene-functionalization of pectin was developed and hydrogels fabricated through UV photoinitiated thiol-norbornene chemistry. This one-pot click reaction was performed in the presence of cells using cell-adhesive and matrix metalloproteinase-sensitive peptides, yielding hydrogels that support extensive cell spreading. Keratinocytes seeded on top of the fibroblast-loaded hydrogel formed a compact epidermis with morphological resemblance to human skin. This work presents a new protease-degradable hydrogel that supports in vitro skin formation with potential for skin tissue engineering.
细胞指令性水凝胶在皮肤修复和再生方面具有吸引力，可作为交互式基质，促进细胞黏附、细胞驱动重塑和细胞外基质成分的重新沉积。本文描述了使用可细胞降解的肽交联剂和整合素特异性黏附配体合成和光交联细胞指令性果胶水凝胶。在真皮成纤维细胞存在下，通过光引发的巯基-降冰片烯点击化学快速形成蛋白酶可降解水凝胶，其具有可调节的性质，并能够调节嵌入细胞的行为，包括细胞扩展、水凝胶收缩和基质金属蛋白酶的分泌。接种在负载成纤维细胞水凝胶上的角质形成细胞能够黏附和形成致密和密集的表皮层，模拟天然皮肤的结构。巯基-烯光交联果胶水凝胶支持全厚皮肤的体外形成，因此是皮肤组织工程应用的极具前景的平台，包括伤口愈合和体外测试模型。
光聚合水凝胶因其对水凝胶形成具有独特的时空控制而在皮肤应用中具有吸引力。本研究报告了一种有前途的光点击果胶水凝胶的设计，其物理化学和生物化学性质可以独立调整以控制细胞行为。开发了一种快速的果胶降冰片烯功能化方法，并通过 UV 光引发的巯基-降冰片烯化学制备水凝胶。该一锅点击反应在细胞存在下使用细胞黏附和基质金属蛋白酶敏感肽进行，生成支持广泛细胞扩展的水凝胶。接种在负载有成纤维细胞的水凝胶顶部的角质形成细胞形成了具有与人皮肤形态相似的致密表皮。这项工作提出了一种新的蛋白酶可降解水凝胶，可支持体外皮肤形成，具有皮肤组织工程的潜力。
