Mesenchymal stem cell-secretome laden photopolymerizable hydrogels for wound healing

IF 3.9 3区 医学 Q2 ENGINEERING, BIOMEDICAL Journal of biomedical materials research. Part A Pub Date : 2024-03-15 DOI:10.1002/jbm.a.37697
Riddhesh B. Doshi, Devashree Vakil, Thomas G. Molley, Md Shariful Islam, Kristopher A. Kilian, Corey Cunningham, Kuldip S. Sidhu
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Abstract

Mesenchymal stem cell-derived secretome represents an emerging acellular therapeutic which possess significant opportunity for clinical applications due to its anti-inflammatory, immunomodulatory, and wound healing properties. However, maintaining therapeutic efficacy and ensuring stability of cell-based products is challenging, requiring a robust delivery method. Therefore, we designed a hydrogel-based scaffold loaded with CK Cell Technologies' proprietary Mesenchymal stem cell-secretome for controlled release treatment of acute and chronic wounds. We incorporated both conditioned media (CM) and extracellular vesicles (EVs) into gelatin methacryloyl (GelMA) hydrogels and demonstrated how we can tune the diffusive release of the EVs from them. To demonstrate viability of the approach, we developed a wound healing scratch assay where we see in situ release of CM and EVs promote enhanced migration of human dermal fibroblasts (hDFs). We see the colocalization of these EVs in the fibroblasts using fluorescent microscopy. Finally, as a surrogate for in vivo neovascularization, we conducted an in vitro tube formation assay for the MSC-secretome using matrigel-embedded human microvascular endothelial cells. By adding CM and EVs, we observe an increase in tubulogenesis. Collectively, our data demonstrates by tuning the GelMA properties, we can influence the controlled release of the MSC-secretome for a wound dressing and bandage application for chronic and acute wounds.

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用于伤口愈合的间充质干细胞-分泌物载体光聚合水凝胶。
间充质干细胞衍生的分泌物代表了一种新兴的细胞疗法,由于其抗炎、免疫调节和伤口愈合的特性,这种疗法在临床应用中拥有巨大的机会。然而,保持疗效并确保细胞基产品的稳定性是一项挑战,需要一种稳健的递送方法。因此,我们设计了一种基于水凝胶的支架,其中装载了 CK 细胞技术公司专有的间充质干细胞分泌物,用于控释治疗急性和慢性伤口。我们在明胶甲基丙烯酰(GelMA)水凝胶中加入了条件培养基(CM)和细胞外囊泡(EVs),并演示了如何调节EVs的扩散释放。为了证明这种方法的可行性,我们开发了一种伤口愈合划痕试验,在这种试验中,我们看到 CM 和 EVs 的原位释放促进了人真皮成纤维细胞(hDFs)的迁移。通过荧光显微镜,我们看到了这些 EVs 在成纤维细胞中的共定位。最后,作为体内新生血管形成的替代物,我们使用matrigel包埋的人微血管内皮细胞进行了间充质干细胞分泌组的体外管形成试验。通过添加 CM 和 EV,我们观察到管生成增加。总之,我们的数据表明,通过调整 GelMA 的特性,我们可以影响间充质干细胞分泌物的可控释放,用于慢性和急性伤口的敷料和绷带应用。
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来源期刊
Journal of biomedical materials research. Part A
Journal of biomedical materials research. Part A 工程技术-材料科学:生物材料
CiteScore
10.40
自引率
2.00%
发文量
135
审稿时长
3.6 months
期刊介绍: The Journal of Biomedical Materials Research Part A is an international, interdisciplinary, English-language publication of original contributions concerning studies of the preparation, performance, and evaluation of biomaterials; the chemical, physical, toxicological, and mechanical behavior of materials in physiological environments; and the response of blood and tissues to biomaterials. The Journal publishes peer-reviewed articles on all relevant biomaterial topics including the science and technology of alloys,polymers, ceramics, and reprocessed animal and human tissues in surgery,dentistry, artificial organs, and other medical devices. The Journal also publishes articles in interdisciplinary areas such as tissue engineering and controlled release technology where biomaterials play a significant role in the performance of the medical device. The Journal of Biomedical Materials Research is the official journal of the Society for Biomaterials (USA), the Japanese Society for Biomaterials, the Australasian Society for Biomaterials, and the Korean Society for Biomaterials. Articles are welcomed from all scientists. Membership in the Society for Biomaterials is not a prerequisite for submission.
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