Winkler Petras, Mao Yong
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
Molecules. 2025 Mar 31;30(7):1577. doi: 10.3390/molecules30071577.
Chronic wounds not only cause significant patient morbidity but also impose a substantial economic burden on the healthcare system. The primary barriers to wound healing include a deficiency of key modulatory factors needed to progress beyond the stalled inflammatory phase and an increased susceptibility to infections. While antimicrobial agents have traditionally been used to treat infections, stem cells have recently emerged as a promising therapy due to their regenerative properties, including the secretion of cytokines and immunomodulators that support wound healing. This study aims to develop an advanced dual-delivery system integrating stem cells and antibiotics. Stem cells have previously been delivered by encapsulation in gelatin methacrylate (GelMA) hydrogels. To explore a more effective delivery method, GelMA was processed into microparticles (MP). Compared to a bulk GelMA hydrogel (HG) encapsulation, GelMA MP supported greater cell growth and enhanced in vitro wound healing activity of human mesenchymal stem cells (hMSCs), likely due to a larger surface area for cell attachment and improved nutrient exchange. To incorporate antimicrobial properties, the broad-spectrum antibiotics penicillin/streptomycin (PS) were loaded into a bulk GelMA hydrogel, which was then cryo-milled into MPs to serve as carriers for hMSCs. To achieve a more sustained antibiotic release, gelatin nanoparticles (NP) were used as carriers for PS. PS was either incorporated during NP synthesis (NP+PS(S)) or absorbed into NP after synthesis (NP+PS(A)). MPs containing PS, NP+PS(S), or NP+PS(A) were tested for their cell carrier functions and antibacterial activities. The incorporation of PS did not compromise the cell-carrying function of MP configurations. The anti- activity was detected in conditioned media from MPs for up to eight days-four days longer than from bulk HG containing PS. Notably, the presence of hMSCs prolonged the antimicrobial activity of MPs, suggesting a synergistic effect between stem cells and antibiotics. PS loaded via synthesis (NP+PS(S)) exhibited a delayed initial release, whereas PS loaded via absorption (NP+PS(A)) provided a more immediate release, with potential for sustained delivery. This study demonstrates the feasibility of a dual-delivery system integrating thera.
慢性伤口不仅会给患者带来严重的发病情况，还会给医疗系统造成巨大的经济负担。伤口愈合的主要障碍包括缺乏使伤口超越停滞的炎症阶段所需的关键调节因子，以及对感染的易感性增加。虽然传统上使用抗菌剂来治疗感染，但干细胞最近因其再生特性，包括分泌支持伤口愈合的细胞因子和免疫调节剂，而成为一种有前景的治疗方法。本研究旨在开发一种整合干细胞和抗生素的先进双递送系统。干细胞此前已通过封装在甲基丙烯酸明胶（GelMA）水凝胶中进行递送。为了探索一种更有效的递送方法，将GelMA加工成微粒（MP）。与块状GelMA水凝胶（HG）封装相比，GelMA MP支持更大的细胞生长，并增强了人间充质干细胞（hMSCs）的体外伤口愈合活性，这可能是由于更大的细胞附着表面积和改善的营养交换。为了赋予抗菌特性，将广谱抗生素青霉素/链霉素（PS）加载到块状GelMA水凝胶中，然后将其冷冻研磨成MP，用作hMSCs的载体。为了实现更持续的抗生素释放，使用明胶纳米颗粒（NP）作为PS的载体。PS要么在NP合成过程中掺入（NP+PS(S)），要么在合成后吸收到NP中（NP+PS(A)）。测试了含有PS、NP+PS(S)或NP+PS(A)的MP的细胞载体功能和抗菌活性。PS的掺入并未损害MP构型的细胞携带功能。在MP的条件培养基中检测到长达八天的抗菌活性——比含有PS的块状HG长四天。值得注意的是，hMSCs的存在延长了MP的抗菌活性，表明干细胞和抗生素之间存在协同作用。通过合成加载的PS（NP+PS(S)）表现出延迟的初始释放，而通过吸收加载的PS（NP+PS(A)）提供了更即时的释放，并具有持续递送的潜力。本研究证明了整合治疗剂的双递送系统的可行性。
