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探索空间限制在免疫细胞募集和皮肤伤口再生中的作用。

Exploring the Role of Spatial Confinement in Immune Cell Recruitment and Regeneration of Skin Wounds.

机构信息

Department of Biomedical Engineering, Duke University, 101 Science Drive Campus Box 90281, Durham, NC, 27708, USA.

Department of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.

出版信息

Adv Mater. 2023 Dec;35(49):e2304049. doi: 10.1002/adma.202304049. Epub 2023 Oct 27.

DOI:10.1002/adma.202304049
PMID:37721722
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10874253/
Abstract

Microporous annealed particle (MAP) scaffolds are injectable granular materials comprised of micron sized hydrogel particles (microgels). The diameter of these microgels directly determines the size of the interconnected void space between particles where infiltrating or encapsulated cells reside. This tunable porosity allows the authors to use MAP scaffolds to study the impact of spatial confinement (SC) on both cellular behaviors and the host response to biomaterials. Despite previous studies showing that pore size and SC influence cellular phenotypes, including mitigating macrophage inflammatory response, there is still a gap in knowledge regarding how SC within a biomaterial modulates immune cell recruitment in vivo in wounds and implants. Thus, the immune cell profile within confined and unconfined biomaterials is studied using small (40 µm), medium (70 µm), and large (130 µm) diameter spherical microgels, respectively. This work uncovered that MAP scaffolds impart regenerative wound healing with an IgG1-biased Th2 response. MAP scaffolds made with large microgels promote a balanced pro-regenerative macrophage response, resulting in enhanced wound healing with mature collagen regeneration and reduced inflammation levels.

摘要

微孔退火颗粒 (MAP) 支架是可注射的颗粒状材料,由微米级水凝胶颗粒 (微凝胶) 组成。这些微凝胶的直径直接决定了颗粒之间相互连通的空隙空间的大小,其中浸润或包裹的细胞存在于该空间内。这种可调节的孔隙率使作者能够使用 MAP 支架来研究空间限制 (SC) 对细胞行为和宿主对生物材料反应的影响。尽管先前的研究表明孔径和 SC 会影响细胞表型,包括减轻巨噬细胞炎症反应,但关于生物材料内的 SC 如何在体内伤口和植入物中调节免疫细胞募集,仍存在知识空白。因此,分别使用小 (40 µm)、中 (70 µm) 和大 (130 µm) 直径的球形微凝胶研究受限和不受限生物材料内的免疫细胞谱。这项工作揭示了 MAP 支架具有再生性伤口愈合作用,并伴有 IgG1 偏向的 Th2 反应。使用大微凝胶制成的 MAP 支架促进了平衡的促再生巨噬细胞反应,导致成熟胶原再生和炎症水平降低的伤口愈合增强。

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