Small 2022, 2200858

间充质干细胞 (MSCs) 对急性肝衰竭 (ALF) 再生具有明显的价值,而其具有长期生物学功能、低免疫反应和高生物相容性的递送策略仍然是一个挑战。复旦大学商珞然课题组制备出了一种负载脂多糖 (LPS) 的光响应性冷冻凝胶多孔微载体 (CPM),用于 MSCs 递送和定植,以促进缺陷肝再生。CPM 由氧化石墨烯、聚(N-异丙基丙烯酰胺)和甲基丙烯酸明胶(GelMA)通过液滴微流体技术和梯度冷却程序。受益于生物相容性 GelMA 组件和 CPM 的多孔微结构,MSC 可以被无损捕获并大量递送。由于 LPS 可以在 NIR 照射下从 CPM 中释放出来,因此交付的 MSC 具有“训练免疫”的特性。因此,当通过生物打印将载有 MSCs 的 CPMs 定制成肝脏匹配的斑块并应用于 ALF 大鼠时,它们显示出比未经训练的 MSCs 更好的抗炎和更显着的肝再生特性。这些特性使 CPMs 成为用于组织修复临床应用的优秀 MSCs 递送系统。

Mesenchymal stem cells (MSCs) have a demonstrated value for acute liver failure (ALF) regeneration, while their delivery stratagems with long-term biological functions, low immune response, and high biocompatibility are still a challenge. Here, a lipopolysaccharide (LPS)-loaded photoresponsive cryogel porous microcarrier(CPM) which fabricated by Luoran Shang’s group from Fudan University  for MSCs delivery and colonization is presented to promote defect liver regeneration,which . The CPMs are fabricated with graphene oxide, poly(N-isopropylacrylamide), and gelatin methacrylate (GelMA) via droplet microfluidic technology and a gradient-cooling procedure. Benefitting from the biocompatible GelMA component and the porous microstructure of the CPMs, MSCs can be nondestructively captured and abundantly delivered. Because the LPS can be released from the CPMs under NIR irradiation, the delivered MSCs are imparted with the feature of “trained immunity.” Thus, when the MSCs-laden CPMs are tailored into the liver matched patches by bioprinting and applied in ALF rats, they display superior anti-inflammatory and more significant liver regeneration properties than the untrained MSCs. These features make the CPMs an excellent MSCs delivery system for clinical applications in tissue repair.


DOI: 10.1002/smll.202200858