In situ forming microporous gelatin methacryloyl hydrogel scaffolds from thermostable microgels for tissue engineering.
In situ forming microporous gelatin methacryloyl hydrogel scaffolds from thermostable microgels for tissue engineering.
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DOI：
10.1002/btm2.10180
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发表时间：
2020-09
影响因子：
7.4
通讯作者：
Sheikhi A
中科院分区：
文献类型：
--
作者：
Zoratto N;Di Lisa D;de Rutte J;Sakib MN;Alves E Silva AR;Tamayol A;Di Carlo D;Khademhosseini A;Sheikhi A
将生物聚合物转化为基于细胞外基质（ECM）的模拟水凝胶支架为设计体外组织/疾病模型和开发损伤组织的再生疗法提供了宝贵的机会。在生物聚合物中，明胶及其可交联衍生物，如明胶甲基丙烯酰（GelMA），由于其模拟ECM的特性，在生物医学应用中具有重要意义。最近，我们基于物理交联GelMA微珠（微凝胶）的化学退火，开发了第一类原位形成的GelMA微孔水凝胶，解决了大块（纳米多孔）GelMA支架的几个关键缺点，包括缺乏相互连接的微米级孔隙来支持按需三维细胞种子和细胞-细胞相互作用。在这里，我们解决了原位形成微孔凝胶的一个限制，即物理交联的构建块在生理温度下的热不稳定性（熔化），导致微孔隙度受损。为了克服这一挑战，我们开发了一种两步制造策略，其中通过半光交联生产耐热的GelMA微珠，然后通过光退火形成稳定的微孔支架。我们发现，半光交联步骤（曝光时间长达90秒，强度为~100 mW/cm2，波长为~365 nm）增加了GelMA微凝胶的热稳定性，同时降低了其支架形成（退火）能力。基于微凝胶和支架稳定性之间的权衡，我们确定了最佳交联条件（暴露时间~60秒），使形成稳定的退火微凝胶支架。这项工作是工程上的一个进步，在原位形成微孔水凝胶由热稳定的GelMA微凝胶组成，在体外和体内应用的生理温度远高于明胶的熔点。
Converting biopolymers to extracellular matrix (ECM)‐mimetic hydrogel‐based scaffolds has provided invaluable opportunities to design in vitro models of tissues/diseases and develop regenerative therapies for damaged tissues. Among biopolymers, gelatin and its crosslinkable derivatives, such as gelatin methacryloyl (GelMA), have gained significant importance for biomedical applications due to their ECM‐mimetic properties. Recently, we have developed the first class of in situ forming GelMA microporous hydrogels based on the chemical annealing of physically crosslinked GelMA microscale beads (microgels), which addressed several key shortcomings of bulk (nanoporous) GelMA scaffolds, including lack of interconnected micron‐sized pores to support on‐demand three‐dimensional‐cell seeding and cell–cell interactions. Here, we address one of the limitations of in situ forming microporous GelMA hydrogels, that is, the thermal instability (melting) of their physically crosslinked building blocks at physiological temperature, resulting in compromised microporosity. To overcome this challenge, we developed a two‐step fabrication strategy in which thermostable GelMA microbeads were produced via semi‐photocrosslinking, followed by photo‐annealing to form stable microporous scaffolds. We show that the semi‐photocrosslinking step (exposure time up to 90 s at an intensity of ~100 mW/cm2 and a wavelength of ~365 nm) increases the thermostability of GelMA microgels while decreasing their scaffold forming (annealing) capability. Hinging on the tradeoff between microgel and scaffold stabilities, we identify the optimal crosslinking condition (exposure time ~60 s) that enables the formation of stable annealed microgel scaffolds. This work is a step forward in engineering in situ forming microporous hydrogels made up from thermostable GelMA microgels for in vitro and in vivo applications at physiological temperature well above the gelatin melting point.
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影响因子：
14
作者：
Nichol, Jason W.;Koshy, Sandeep T.;Bae, Hojae;Hwang, Chang M.;Yamanlar, Seda;Khademhosseini, Ali
通讯作者：
Khademhosseini, Ali
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Chan-Park, Mary B.
影响因子：
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作者：
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通讯作者：
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