Department of Biomedical Engineering, Texas A&M University, College Station, Texas 77843, United States.
Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843, United States.
Biomacromolecules. 2024 Sep 9;25(9):5798-5808. doi: 10.1021/acs.biomac.4c00465. Epub 2024 Aug 27.
Microporous annealed particle (MAP) hydrogels are a promising class of in situ-forming scaffolds for tissue repair and regeneration. While an expansive toolkit of annealing chemistries has been described, the effects of different annealing chemistries on MAP hydrogel properties and performance have not been studied. In this study, we address this gap through a controlled head-to-head comparison of poly(ethylene glycol) (PEG)-based MAP hydrogels that were annealed using tetrazine-norbornene and thiol-norbornene click chemistry. Characterization of material properties revealed that tetrazine click annealing significantly increases MAP hydrogel shear storage modulus and results in slower in vitro degradation kinetics when microgels with a higher cross-link density are used. However, these effects are muted when the MAP hydrogels are fabricated from microgels with a lower cross-link density. In contrast, in vivo testing in murine critical-sized calvarial defects revealed that these differences in physicochemical properties do not translate to differences in bone volume or calvarial defect healing when growth-factor-loaded MAP hydrogel scaffolds are implanted into mouse calvarial defects. Nonetheless, the impact of tetrazine click annealing could be important in other applications and should be investigated further.
微孔退火颗粒 (MAP) 水凝胶是一种很有前途的组织修复和再生的原位形成支架。虽然已经描述了广泛的退火化学工具箱，但不同的退火化学对 MAP 水凝胶性质和性能的影响尚未得到研究。在这项研究中，我们通过对使用四嗪-降冰片烯和巯基-降冰片烯点击化学进行退火的基于聚乙二醇 (PEG) 的 MAP 水凝胶进行对照研究来解决这一差距。材料性质的表征表明，四嗪点击退火显著提高了 MAP 水凝胶的剪切储能模量，并导致具有更高交联密度的微凝胶的体外降解动力学减慢。然而，当 MAP 水凝胶由交联密度较低的微凝胶制成时，这些影响就会减弱。相比之下，在小鼠临界尺寸颅骨缺损中的体内测试表明，当将载有生长因子的 MAP 水凝胶支架植入小鼠颅骨缺损中时，这些物理化学性质的差异不会转化为骨体积或颅骨缺损愈合的差异。尽管如此，四嗪点击退火的影响在其他应用中可能很重要，应该进一步研究。
