Guerra Alberto Daniel, Rose Warren E, Hematti Peiman, Kao W John
School of Pharmacy, Division of Pharmaceutical Sciences, Pharmacy Practice Division, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI 53705, USA.
School of Medicine and Public Health, Department of Medicine, Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, 1685 Highland Avenue, Madison, WI 53705, USA.
Acta Biomater. 2017 Mar 15;51:184-196. doi: 10.1016/j.actbio.2017.01.021. Epub 2017 Jan 7.
Mesenchymal stromal/stem cells (MSCs) have demonstrated pro-healing properties including an anti-inflammatory cytokine profile and the promotion of angiogenesis via expression of growth factors in pre-clinical models. MSCs encapsulated in poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) crosslinked hydrogels have led to controlled cellular presentation at wound sites with favorable wound healing outcomes. However, the therapeutic potential of MSC-loaded hydrogels may be limited by non-specific protein adsorption on the delivery matrix that could facilitate the initial adhesion of microorganisms and subsequent virulent biofilm formation. Antimicrobials loaded concurrently in the hydrogels with MSCs could reduce microbial bioburden and promote healing, but the antimicrobial effect on the MSC wound healing capacity and the antibacterial efficacy of the hydrogels is unknown. We demonstrate that minocycline specifically induces a favorable change in MSC migration capacity, proliferation, gene expression, extracellular matrix (ECM) attachment, and adhesion molecule and growth factor release with subsequent increased angiogenesis. We then demonstrate that hydrogels loaded with MSCs, minocycline, vancomycin, and linezolid can significantly decrease bacterial bioburden. Our study suggests that minocycline can serve as a dual mechanism for the regenerative capacity of MSCs and the reduction of bioburden in triple antimicrobial-loaded hydrogels.
Wound healing is a complex biological process that can be hindered by bacterial infection, excessive inflammation, and inadequate microvasculature. In this study, we develop a new formulation of poly(ethylene glycol) diacrylate and thiolated gelatin poly(ethylene glycol) crosslinked hydrogels loaded with minocycline, vancomycin, linezolid, and mesenchymal stromal/stem cells that induces a favorable wound healing phenotype in mesenchymal stromal/stem cells and prevents bacterial bioburden on the hydrogel. This combinatorial approach to biomaterial development has the potential to impact wound healing for contaminated full thickness cutaneous wounds.
间充质基质/干细胞（MSC）已在临床前模型中展现出促进愈合的特性，包括抗炎细胞因子谱以及通过生长因子表达促进血管生成。封装在聚（乙二醇）二丙烯酸酯（PEGdA）和硫醇化明胶聚（乙二醇）（Gel-PEG-Cys）交联水凝胶中的MSC已实现伤口部位细胞的可控呈现，并取得了良好的伤口愈合效果。然而，负载MSC的水凝胶的治疗潜力可能会受到递送基质上非特异性蛋白质吸附的限制，这种吸附可能会促进微生物的初始粘附以及随后形成有毒生物膜。与MSC同时负载在水凝胶中的抗菌剂可以减少微生物生物负荷并促进愈合，但抗菌剂对MSC伤口愈合能力的影响以及水凝胶的抗菌功效尚不清楚。我们证明米诺环素能特异性地诱导MSC迁移能力、增殖、基因表达、细胞外基质（ECM）附着以及粘附分子和生长因子释放发生有利变化，随后血管生成增加。然后我们证明负载有MSC、米诺环素、万古霉素和利奈唑胺的水凝胶可以显著降低细菌生物负荷。我们的研究表明，米诺环素可作为一种双重机制，用于增强MSC的再生能力以及减少三重抗菌负载水凝胶中的生物负荷。
伤口愈合是一个复杂的生物学过程，可能会受到细菌感染、过度炎症和微血管不足的阻碍。在本研究中，我们开发了一种新的聚（乙二醇）二丙烯酸酯和硫醇化明胶聚（乙二醇）交联水凝胶配方，负载米诺环素、万古霉素、利奈唑胺和间充质基质/干细胞，该配方可诱导间充质基质/干细胞呈现出有利的伤口愈合表型，并防止水凝胶上的细菌生物负荷。这种生物材料开发的组合方法有可能影响污染的全层皮肤伤口的愈合。
