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用于肌腱再生的含酮戊二酸单甲酯（Oxo-M）和4-吡啶基-4-苄基丁酸酯（4-PPBP）的多结构域肽水凝胶

Oxo-M and 4-PPBP Delivery Multi-Domain Peptide Hydrogel Toward Tendon Regeneration.

作者信息

Park Ga Young, Tarafder Solaiman, Eyen Samantha Lewis, Park Soomin, Kim Ryunhyung, Siddiqui Zain, Kumar Vivek, Lee Chang H

机构信息

Regenerative Engineering Laboratory, Center for Dental and Craniofacial Research, Columbia University Irving Medical Center, New York, NY, United States.

Department of Bio-Medical Engineering, New Jersey Institute of Technology, Hoboken, NJ, United States.

出版信息

Front Bioeng Biotechnol. 2022 Jan 27;10:773004. doi: 10.3389/fbioe.2022.773004. eCollection 2022.

DOI:10.3389/fbioe.2022.773004
PMID:35155388
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8829701/
Abstract

We have recently identified novel small molecules, Oxo-M and 4-PPBP, which specifically stimulate endogenous tendon stem/progenitor cells (TSCs), leading to potential regenerative healing of fully transected tendons. Here, we investigated an injectable, multidomain peptide (MDP) hydrogel providing controlled delivery of the small molecules for regenerative tendon healing. We investigated the release kinetics of Oxo-M and 4-PPBP from MDP hydrogels and the effect of MDP-released small molecules on tenogenic differentiation of TSCs and tendon healing. , MDP showed a sustained release of Oxo-M and 4-PPBP and a slower degradation than fibrin. In addition, tenogenic gene expression was significantly increased in TSC with MDP-released Oxo-M and 4-PPBP as compared to the fibrin-released. , MDP releasing Oxo-M and 4-PPBP significantly improved tendon healing, likely associated with prolonged effects of Oxo-M and 4-PPBP on suppression of M1 macrophages and promotion of M2 macrophages. Comprehensive analyses including histomorphology, digital image processing, and modulus mapping with nanoindentation consistently suggested that Oxo-M and 4-PPBP delivered via MDP further improved tendon healing as compared to fibrin-based delivery. In conclusion, MDP delivered with Oxo-M and 4-PPBP may serve as an efficient regenerative therapeutic for tendon regeneration and healing.

摘要

我们最近鉴定出了新型小分子，即氧代-M（Oxo-M）和4-苯基-4-苯并吡喃酮（4-PPBP），它们能特异性刺激内源性肌腱干/祖细胞（TSCs），从而实现完全横断肌腱的潜在再生愈合。在此，我们研究了一种可注射的多结构域肽（MDP）水凝胶，其能为再生肌腱愈合提供小分子的可控释放。我们研究了Oxo-M和4-PPBP从MDP水凝胶中的释放动力学，以及MDP释放的小分子对TSCs成腱分化和肌腱愈合的影响。结果显示，MDP能持续释放Oxo-M和4-PPBP，且降解速度比纤维蛋白慢。此外，与纤维蛋白释放组相比，用MDP释放的Oxo-M和4-PPBP处理的TSCs中成腱基因表达显著增加。而且，释放Oxo-M和4-PPBP的MDP显著改善了肌腱愈合，这可能与Oxo-M和4-PPBP对M1巨噬细胞的抑制和M2巨噬细胞的促进作用的延长有关。包括组织形态学、数字图像处理和纳米压痕模量映射在内的综合分析一致表明，与基于纤维蛋白的递送相比，通过MDP递送的Oxo-M和4-PPBP进一步改善了肌腱愈合。总之，与Oxo-M和4-PPBP一起递送的MDP可能作为一种有效的再生疗法用于肌腱再生和愈合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d9/8829701/623d09984de4/fbioe-10-773004-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d9/8829701/49f74033426d/fbioe-10-773004-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d9/8829701/19c0e083270d/fbioe-10-773004-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d9/8829701/8b532cf73617/fbioe-10-773004-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d9/8829701/5b41124099d5/fbioe-10-773004-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d9/8829701/623d09984de4/fbioe-10-773004-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d9/8829701/49f74033426d/fbioe-10-773004-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d9/8829701/19c0e083270d/fbioe-10-773004-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d9/8829701/8b532cf73617/fbioe-10-773004-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d9/8829701/5b41124099d5/fbioe-10-773004-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88d9/8829701/623d09984de4/fbioe-10-773004-g005.jpg

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Macrophage depletion impairs neonatal tendon regeneration.巨噬细胞耗竭可损害新生儿肌腱再生。
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Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats.脂肪来源的人血管周围干细胞可能改善大鼠跟腱愈合。
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