Taghdi Manal Hussein, Al-Masawa Maimonah Eissa, Muttiah Barathan, Fauzi Mh Busra, Law Jia Xian, Zainuddin Ani Amelia, Lokanathan Yogeswaran
Department of Tissue Engineering and Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia.
Department of Anesthesia and Intensive Care, Faculty of Medical Technology, University of Tripoli, Tripoli P.O. Box 13932, Libya.
Polymers (Basel). 2025 Apr 24;17(9):1163. doi: 10.3390/polym17091163.
Mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) have shown great promise in promoting tissue repair, including skin wound healing, but challenges like rapid degradation and short retention have limited their clinical application. Hydrogels have emerged as effective carriers for sustained EV release. Three-dimensional printing enables the development of personalized skin substitutes tailored to the wound size and shape. This study aimed to develop 3D bioprinted gelatin-genipin hydrogels incorporating human umbilical cord MSC-sEVs (hUCMSC-sEVs) for future skin wound healing applications. Gelatin hydrogels (8% and 10% /) were crosslinked with 0.3% genipin (GECL) to improve stability. The hydrogels were evaluated for their suitability for extrusion-based 3D bioprinting and physicochemical properties, such as the swelling ratio, hydrophilicity, enzymatic degradation, and water vapor transmission rate (WVTR). Chemical characterization was performed using EDX, XRD, and FTIR. The hUCMSC-sEVs were isolated via centrifugation and tangential flow filtration (TFF) and characterized. The crosslinked hydrogels were successfully 3D bioprinted and demonstrated superior properties, including high hydrophilicity, a swelling ratio of ~500%, slower degradation, and optimal WVTR. hUCMSC-sEVs, ranging from 50 to 200 nm, were positive for surface and cytosolic markers. Adding 75 μg/mL of hUCMSC-EVs into 10% GECL hydrogels significantly improved the biocompatibility. These hydrogels offer ideal properties for 3D bioprinting and wound healing, demonstrating their potential as biomaterial scaffolds for skin tissue regeneration applications.
间充质基质细胞衍生的小细胞外囊泡（MSC-sEVs）在促进组织修复（包括皮肤伤口愈合）方面显示出巨大潜力，但快速降解和滞留时间短等挑战限制了其临床应用。水凝胶已成为用于持续释放细胞外囊泡的有效载体。三维打印能够开发出根据伤口大小和形状定制的个性化皮肤替代物。本研究旨在开发一种包含人脐带MSC-sEVs（hUCMSC-sEVs）的3D生物打印明胶-京尼平水凝胶，用于未来的皮肤伤口愈合应用。将明胶水凝胶（8%和10%/）与0.3%京尼平（GECL）交联以提高稳定性。对水凝胶进行评估，以确定其是否适合基于挤出的3D生物打印以及其物理化学性质，如溶胀率、亲水性、酶降解和水蒸气透过率（WVTR）。使用能谱仪（EDX）、X射线衍射仪（XRD）和傅里叶变换红外光谱仪（FTIR）进行化学表征。通过离心和切向流过滤（TFF）分离hUCMSC-sEVs并进行表征。交联水凝胶成功进行了3D生物打印，并表现出优异的性能，包括高亲水性、约500%的溶胀率、较慢的降解速度和最佳的WVTR。hUCMSC-sEVs大小在50至200纳米之间，表面和胞质标志物呈阳性。向10% GECL水凝胶中添加75μg/mL的hUCMSC-EVs可显著提高生物相容性。这些水凝胶为3D生物打印和伤口愈合提供了理想的性能，证明了它们作为皮肤组织再生应用生物材料支架的潜力。
