Collagen scaffolds derived from bovine skin loaded with MSC optimized M1 macrophages remodeling and chronic diabetic wounds healing.
Collagen scaffolds derived from bovine skin loaded with MSC optimized M1 macrophages remodeling and chronic diabetic wounds healing.
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来自牛皮肤的胶原蛋白支架装载有 MSC 优化的 M1 巨噬细胞重塑和慢性糖尿病伤口愈合
DOI：
10.1002/btm2.10467
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发表时间：
2023-05
影响因子：
7.4
通讯作者：
Xie, Julin
中科院分区：
文献类型：
--
作者：
Liu, Hengdeng;Yang, Ronghua;Zhao, Shixin;Zhou, Fei;Liu, Yiling;Zhou, Ziheng;Chen, Lei;Xie, Julin
摘要慢性糖尿病创面因炎症微环境持续存在，真皮组织稀少，不易愈合，复发率高。因此，迫切需要一种能够诱导快速组织再生和抑制瘢痕形成的真皮替代物来解决这一问题。在本研究中，我们将新型动物组织源性胶原真皮替代支架(CDRs)与骨髓间充质干细胞(BMSCs)相结合，建立了具有生物活性的真皮替代物(BADS)，用于慢性糖尿病创面的愈合和复发治疗。牛皮来源的胶原支架具有良好的物理化学性质和良好的生物相容性。负载BMSCs的CBS(CBS-MCSs)在体外可抑制M1巨噬细胞的极化。CBS-MSCs处理的M1巨噬细胞在蛋白水平检测到MMP9的减少和COL3的增加，这可能是由于抑制了M1巨噬细胞的肿瘤坏死因子-α/核因子-κB信号通路(下调磷酸化的IKKα/β/总的IKKα/β、磷酸化的IκB/总的IκB和磷酸化的核因子κB/总的核因子κB)。此外，CBS-MSCs还可促进M1(下调iNOS)向M2(上调CD206)巨噬细胞的转化。创面愈合评价显示，骨髓间充质干细胞可调节db/db小鼠巨噬细胞的极化和炎症因子(促炎因子：IL-1β、肿瘤坏死因子-α和基质金属蛋白酶-9；抗炎因子：IL-10和转化生长因子-β3)的平衡。此外，CBS-MSCs促进了慢性糖尿病创面的非收缩和再上皮化过程、肉芽组织再生和新生血管。因此，CBS-MSCs在促进糖尿病慢性创面愈合和预防溃疡复发方面具有潜在的临床应用价值。
Abstract Owing to the persistent inflammatory microenvironment and unsubstantial dermal tissues, chronic diabetic wounds do not heal easily and their recurrence rate is high. Therefore, a dermal substitute that can induce rapid tissue regeneration and inhibit scar formation is urgently required to address this concern. In this study, we established biologically active dermal substitutes (BADS) by combining novel animal tissue‐derived collagen dermal‐replacement scaffolds (CDRS) and bone marrow mesenchymal stem cells (BMSCs) for the healing and recurrence treatments of chronic diabetic wounds. The collagen scaffolds derived from bovine skin (CBS) displayed good physicochemical properties and superior biocompatibility. CBS loaded with BMSCs (CBS‐MCSs) could inhibit M1 macrophage polarization in vitro. Decreased MMP‐9 and increased Col3 at the protein level were detected in CBS‐MSCs‐treated M1 macrophages, which may be attributed to the suppression of the TNF‐α/NF‐κB signaling pathway (downregulating phospho‐IKKα/β/total IKKα/β, phospho‐IκB/total IκB, and phospho‐NFκB/total NFκB) in M1 macrophages. Moreover, CBS‐MSCs could benefit the transformation of M1 (downregulating iNOS) to M2 (upregulating CD206) macrophages. Wound‐healing evaluations demonstrated that CBS‐MSCs regulated the polarization of macrophages and the balance of inflammatory factors (pro‐inflammatory: IL‐1β, TNF‐α, and MMP‐9; anti‐inflammatory: IL‐10 and TGF‐β3) in db/db mice. Furthermore, CBS‐MSCs facilitated the noncontractile and re‐epithelialized processes, granulation tissue regeneration, and neovascularization of chronic diabetic wounds. Thus, CBS‐MSCs have a potential value for clinical application in promoting the healing of chronic diabetic wounds and preventing the recurrence of ulcers.
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影响因子：
41.2
作者：
Griffin DR;Archang MM;Kuan CH;Weaver WM;Weinstein JS;Feng AC;Ruccia A;Sideris E;Ragkousis V;Koh J;Plikus MV;Di Carlo D;Segura T;Scumpia PO
通讯作者：
Scumpia PO
影响因子：
5.2
作者：
Everett E;Mathioudakis N
通讯作者：
Mathioudakis N
影响因子：
29
作者：
Cereijo, Ruben;Gavalda-Navarro, Aleix;Villarroya, Francesc
通讯作者：
Villarroya, Francesc
影响因子：
18.9
作者：
Hauck S;Zager P;Halfter N;Wandel E;Torregrossa M;Kakpenova A;Rother S;Ordieres M;Räthel S;Berg A;Möller S;Schnabelrauch M;Simon JC;Hintze V;Franz S
通讯作者：
Franz S
影响因子：
10.2
作者：
Chato-Astrain J;Chato-Astrain I;Sánchez-Porras D;García-García ÓD;Bermejo-Casares F;Vairo C;Villar-Vidal M;Gainza G;Villullas S;Oruezabal RI;Ponce-Polo Á;Garzón I;Carriel V;Campos F;Alaminos M
通讯作者：
Alaminos M