Heparin Microislands in Microporous Annealed Particle Scaffolds for Accelerated Diabetic Wound Healing
Heparin Microislands in Microporous Annealed Particle Scaffolds for Accelerated Diabetic Wound Healing
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DOI：
10.1002/adfm.202104337
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发表时间：
2021-06-18
影响因子：
19
通讯作者：
Griffin, Donald R.
中科院分区：
文献类型：
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作者：
Pruett, Lauren J.;Jenkins, Christian H.;Griffin, Donald R.
模拟生长因子-细胞外基质相互作用促进细胞迁移是改善组织与生物材料支架整合以促进受损组织再生的有力技术。这是通过支架介导的外源生长因子的受控传递来尝试的；然而，这种传递的预定性质会限制支架满足每个伤口独特的时空再生需求的能力，并存在翻译障碍。为了解决这一局限性，提出了一种新的生长因子组织方法，它结合了肝素微岛(Mu岛)，它是空间上隔离的含肝素的微粒，可以在体外通过微尺度的异质隔离来重组和保护内源性局部生长因子，从而改善伤口愈合的功能。更具体地说，肝素Mu岛被结合到微孔退火颗粒支架中，这使得可以通过微粒子亚群的比率混合来方便地调节微环境的异质性。在这篇手稿中，肝素在体外证明了肝素对应用的生长因子的异相隔离和控制下游细胞迁移的能力。此外，与两个临床相关的对照相比，他们在糖尿病伤口模型中显著改善伤口愈合结果(表皮再生和再血管形成)的能力被提出。
Mimicking growth factor-extracellular matrix interactions for promoting cell migration is a powerful technique to improve tissue integration with biomaterial scaffolds for the regeneration of damaged tissues. This is attempted by scaffold-mediated controlled delivery of exogenous growth factors; however, the predetermined nature of this delivery can limit the scaffold's ability to meet each wound's unique spatiotemporal regenerative needs and presents translational hurdles. To address this limitation, a new approach to growth factor organization is presented that incorporates heparin microislands (mu Islands), which are spatially isolated heparin-containing microparticles that can reorganize and protect endogenous local growth factors via heterogeneous sequestration at the microscale in vitro and result in functional improvements in wound healing. More specifically, the heparin mu Islands are incorporated within microporous annealed particle scaffolds, which allows facile tuning of microenvironment heterogeneity through ratiometric mixing of microparticle sub-populations. In this manuscript, the ability of heparin mu Islands to heterogeneously sequester applied growth factor and control downstream cell migration in vitro is demonstrated. Further, their ability to significantly improve wound healing outcomes (epidermal regeneration and re-vascularization) in a diabetic wound model relative to two clinically relevant controls is presented.