Das Priya, Maresch Martin, Dey Nigamananda, Sulaiman Noof, Ashour Amr Gamal, Ammar Hamad M, Basem Mohammed, Al Muharraqi Mohammed A, McGrath Matthew, Jacob Melvin Varghese, O'Brien Fergal J, Keogh Michael B
TERG Bahrain, School of Postgraduate Studies and Research, Royal College of Surgeons in Ireland, Manama, Kingdom of Bahrain.
RMS Royal Medical Services, Riffa, Kingdom of Bahrain.
APL Bioeng. 2025 Apr 25;9(2):026112. doi: 10.1063/5.0240504. eCollection 2025 Jun.
Aging can prolong the wound healing and is associated with decline in stem cells, delays in cellular migration, and lower vascularization. Tissue engineering has largely evolved to incorporate advanced three-dimensional wound dressings, scaffolds, and hydrogels that may be seeded with mesenchymal stromal cells (MSCs) to foster an environment conducive to regeneration and enhance the healing process. The effectiveness of stem cell-seeded scaffolds can be improved by incorporating activating agents such as nucleic acids resulting in gene-activated scaffolds (GAS), thereby facilitating targeted wound healing in aged patients. In this study, we assess the wound healing potential of a promising MSC seeded gene-activated collagen scaffold, containing the anti-fibrotic agent β-klotho and pro-angiogenic stromal derived factor (SDF-1α) in aged male Sprague Dawley rats (20-24 month old). A MSC cell loaded split skin model compared MSC only with the clinical standard dressing +Jelonet, MSCs +gene-free collagen scaffold, and MSCs +SDF-1α/β-klotho dual gene-activated collagen scaffold up to 21 days. Our results showed wound healing in all groups except in MSC +Jelonet which showed scab formation with exudate. MSC only group healed primarily via fibrotic contraction. In contrast, the scaffold groups showed host tissue integration and a redistribution of extracellular matrix proteins, less contraction, and complete re-epithelized wounds at day 21. The dual GAS displayed programmed wound healing with the greatest neo-vascularization CD31 expression. In conclusion, wound healing in aged rats can be effectively modulated when MSCs are loaded on biocompatible collagen scaffolds, particularly when these scaffolds are loaded with anti-fibrotic and pro-angiogenic factors. This approach enhances blood vessel formation while reducing fibrosis, suggesting a promising potential for programmed wound healing strategies in aged chronic wounds.
衰老会延长伤口愈合时间，且与干细胞数量减少、细胞迁移延迟和血管生成减少有关。组织工程学已在很大程度上发展为采用先进的三维伤口敷料、支架和水凝胶，这些材料可接种间充质基质细胞（MSC），以营造有利于再生的环境并加速愈合过程。通过加入核酸等激活剂构建基因激活支架（GAS），可提高接种干细胞的支架的有效性，从而促进老年患者的靶向伤口愈合。在本研究中，我们评估了一种有前景的接种MSC的基因激活胶原支架在老年雄性Sprague Dawley大鼠（20 - 24月龄）中的伤口愈合潜力，该支架含有抗纤维化剂β-klotho和促血管生成的基质衍生因子（SDF-1α）。一个接种MSC的裂皮模型将仅接种MSC的情况与临床标准敷料+Jelonet、MSC +无基因胶原支架以及MSC +SDF-1α/β-klotho双基因激活胶原支架进行了长达21天的比较。我们的结果显示，除了MSC +Jelonet组出现结痂并伴有渗出液外，其他所有组均实现了伤口愈合。仅接种MSC的组主要通过纤维化收缩实现愈合。相比之下，支架组在第21天时显示出宿主组织整合以及细胞外基质蛋白的重新分布，收缩较少，伤口完全重新上皮化。双基因激活支架表现出程序性伤口愈合，新生血管化的CD31表达最高。总之，当MSC负载于生物相容性胶原支架上时，老年大鼠的伤口愈合可得到有效调节，尤其是当这些支架负载抗纤维化和促血管生成因子时。这种方法在减少纤维化的同时增强了血管形成，表明在老年慢性伤口的程序性伤口愈合策略方面具有广阔的应用前景。
