Subcutaneously Engineered Decalcified Bone Matrix Xenografts Promote Bone Repair by Regulating the Immune Microenvironment, Prevascularization, and Stem Cell Homing,ACS Biomaterials Science & Engineering

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Subcutaneously Engineered Decalcified Bone Matrix Xenografts Promote Bone Repair by Regulating the Immune Microenvironment, Prevascularization, and Stem Cell Homing
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2023-12-27 , DOI: 10.1021/acsbiomaterials.3c01331
Qingqing Pan ₁ , Pei Zhang ₁ , Fei Xue ₁ , Jingxuan Zhang ₁ , Zhenlin Fan ₁ , Zhanyu Chang ₁ , Zhuo Liang ₁ , Guangdong Zhou ₂ , Wenjie Ren ₁

Affiliation

Immunoregulatory and vascularized microenvironments play an important role in bone regeneration; however, the precise regulation for vascularization and inflammatory reactions remains elusive during bone repair. In this study, by means of subcutaneous preimplantation, we successfully constructed demineralized bone matrix (DBM) grafts with immunoregulatory and vascularized microenvironments. According to the current results, at the early time points (days 1 and 3), subcutaneously implanted DBM grafts recruited a large number of pro-inflammatory M1 macrophages with positive expression of CD68 and iNOS, while at the later time points (days 7 and 14), these inflammatory cells gradually subsided, accompanying increased presence of anti-inflammatory M2 macrophages with positive expression of CD206 and Arg-1, indicating a gradually enhanced anti-inflammatory microenvironment. At the same time, the gradually increased angiogenesis was observed in the DBM grafts with implantation time. In addition, the positive cells of CD105, CD73, and CD90 were observed in the inner region of the DBM grafts, implying the homing of mesenchymal stem cells. The repair results of cranial bone defects in a rat model further confirmed that the subcutaneous DBM xenografts at 7 days significantly improved bone regeneration. In summary, we developed a simple and novel strategy for bone regeneration mediated by anti-inflammatory microenvironment, prevascularization, and endogenous stem cell homing.

中文翻译：

皮下工程脱钙骨基质异种移植物通过调节免疫微环境、预血管化和干细胞归巢促进骨修复

免疫调节和血管化微环境在骨再生中发挥重要作用；然而，骨修复过程中血管形成和炎症反应的精确调节仍然难以捉摸。在本研究中，通过皮下预植入的方式，我们成功构建了具有免疫调节和血管化微环境的脱矿骨基质（DBM）移植物。根据目前的结果，在早期时间点（第1天和第3天），皮下植入的DBM移植物招募了大量CD68和iNOS阳性表达的促炎M1巨噬细胞，而在后期时间点（第7天和第7天）， (14)，这些炎症细胞逐渐消退，伴随着CD206和Arg-1阳性表达的抗炎M2巨噬细胞的增加，表明抗炎微环境逐渐增强。同时，随着植入时间的延长，DBM移植物中的血管生成逐渐增加。此外，在DBM移植物的内部区域观察到CD105、CD73和CD90的阳性细胞，这意味着间充质干细胞的归巢。大鼠模型颅骨缺损的修复结果进一步证实，皮下DBM异种移植物在7天时显着改善了骨再生。总之，我们开发了一种简单而新颖的由抗炎微环境、预血管化和内源干细胞归巢介导的骨再生策略。

更新日期：2023-12-27

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