Click by Click Microporous Annealed Particle (MAP) Scaffolds
Click by Click Microporous Annealed Particle (MAP) Scaffolds
复制标题
Click by Click微孔退火颗粒（MAP）支架
DOI：
10.1002/adhm.201901391
复制
发表时间：
2020-04-24
影响因子：
10
通讯作者：
Segura, Tatiana
中科院分区：
文献类型：
--
作者：
Darling, Nicole J.;Xi, Weixian;Segura, Tatiana
大孔支架越来越多地应用于再生医学和组织修复。虽然最近开发的微孔退火颗粒(MAP)支架克服了可注射性和原位水凝胶形成的问题，但在可调整性方面仍然存在局限性，无法控制水凝胶的强度和刚性，以适用于广泛的应用。为了解决这些关键问题，本文利用硫醇-降冰片烯点击反应合成了透明质酸(HA)的水凝胶微粒(HMPs)，然后利用四嗪降冰片烯点击反应将HMPs热处理成多孔支架。这种组装方法允许通过改变四嗪与降冰片烯的比例来直接调整整体支架的刚性，增加四嗪会增加支架的储存弹性系数、杨氏模量和最大应力。这些变化与空泡率无关。进一步将人真皮成纤维细胞纳入多孔支架中，揭示了这种退火法的生物相容性以及增殖和细胞占有量的差异。最后，将多孔HA-Tet MAP支架注射到缺血性中风模型中，表明这种化学物质在体内是生物相容的，并减少了炎症和星形胶质细胞增生的水平，正如之前对其他交联化学物质所证明的那样。
Macroporous scaffolds are being increasingly used in regenerative medicine and tissue repair. While the recently developed microporous annealed particle (MAP) scaffolds have overcome issues with injectability and in situ hydrogel formation, limitations with respect to tunability to be able to manipulate hydrogel strength and rigidity for broad applications still exist. To address these key issues, here hydrogel microparticles (HMPs) of hyaluronic acid (HA) are synthesized using the thiol-norbornene click reaction and then HMPs are subsequently annealed into a porous scaffold using the tetrazine-norbornene click reaction. This assembly method allows for straightforward tuning of bulk scaffold rigidity by varying the tetrazine to norbornene ratio, with increasing tetrazine resulting in increasing scaffold storage modulus, Young's modulus, and maximum stress. These changes are independent of void fraction. Further incorporation of human dermal fibroblasts throughout the porous scaffold reveals the biocompatibility of this annealing strategy as well as differences in proliferation and cell-occupied volume. Finally, injection of porous HA-Tet MAP scaffolds into an ischemic stroke model shows this chemistry is biocompatible in vivo with reduced levels of inflammation and astrogliosis as previously demonstrated for other crosslinking chemistries.