Department of Surgery, Faculty of Medicine, Université Laval, Québec, QC, Canada; Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Québec, QC, Canada; CHU de Québec - Université Laval Research Center, Québec, QC, Canada.
Department of Surgery, Faculty of Medicine, Université Laval, Québec, QC, Canada; Centre de recherche en organogénèse expérimentale de l'Université Laval/LOEX, Québec, QC, Canada; CHU de Québec - Université Laval Research Center, Québec, QC, Canada.
Acta Biomater. 2023 Sep 1;167:249-259. doi: 10.1016/j.actbio.2023.05.053. Epub 2023 Jun 5.
Patients with deep and extensive wounds need urgent skin coverage to re-establish the cutaneous barrier that prevents life-threatening infections and dehydration. However, the current clinically-available skin substitutes intended for permanent coverage are limited in number, and a trade-off between production time and quality must be made. Here, we report the use of decellularized self-assembled dermal matrices to reduce by half the manufacturing process time of clinical-grade skin substitutes. These decellularized matrices can be stored for over 18 months and recellularized with patients' cells in order to generate skin substitutes that show outstanding histological and mechanical properties in vitro. Once grafted in mice, these substitutes persist over weeks with high graft take, few contraction events, and high stem cell content. These next-generation skin substitutes constitute a substantial advancement in the treatment of major burn patients, combining, for the first time, high functionality, rapid manufacturability and easy handling for surgeons and healthcare practitioners. Future clinical trials will be conducted to assess the advantages of these substitutes over existing treatments. STATEMENT OF SIGNIFICANCE: The number of patients in need for organ transplantation is ever-growing and there is a shortage in tissue and organ donors. In this study, we show for the first time that we can preserve decellularized self-assembled tissues and keep them in storage. Then, in only three weeks we can use them to produce bilayered skin substitutes that have properties very close to those of the native human skin. These findings therefore represent a major step forward in the field of tissue engineering and organ transplantation, paving the way toward a universal off-the-shelf biomaterial for tissue reconstruction and surgery that will be beneficial for many clinicians and patients.
患有深度和广泛伤口的患者需要紧急的皮肤覆盖物来重建防止危及生命的感染和脱水的皮肤屏障。然而，目前临床上可用于永久性覆盖的皮肤替代品数量有限，必须在生产时间和质量之间进行权衡。在这里，我们报告使用去细胞自组装真皮基质将临床级皮肤替代品的制造过程时间缩短一半。这些去细胞基质可以储存超过 18 个月，并可以与患者的细胞重新细胞化，以生成在体外显示出出色的组织学和机械性能的皮肤替代品。一旦在小鼠中移植，这些替代品在数周内持续存在，移植物成活率高、收缩事件少且干细胞含量高。这些下一代皮肤替代品在治疗大面积烧伤患者方面取得了重大进展，首次结合了高功能、快速可制造性和易于外科医生和医疗保健从业者处理的特点。未来将进行临床试验，以评估这些替代品相对于现有治疗方法的优势。意义声明：需要进行器官移植的患者人数不断增加，而组织和器官供体短缺。在这项研究中，我们首次表明，我们可以保存去细胞自组装组织并将其储存在存储库中。然后，我们只需三个星期就可以使用它们来生产双层皮肤替代品，其性能非常接近天然人体皮肤。因此，这些发现代表了组织工程和器官移植领域的重大进展，为组织重建和手术的通用现成生物材料铺平了道路，这将使许多临床医生和患者受益。
