Abstract：
Diabetic wounds are hard-to-heal due to complex multifactorial dysregulation within the micro-environment, necessitating the development of novel regenerative approaches to stimulate healing. This study investigated whether the combined therapeutic application of two novel cellular tissue products, namely a decellularized collagen-rich amniotic membrane (AmR) and growth factor-rich umbilical cord blood serum (UCBS) could have a positive synergistic effect on long-term healing outcomes by stimulating both superficial wound closure and wound bed regeneration. Full thickness excisional wounds were induced on obese diabetic mice (B6.Cg-lepob/J, ob/ob, n = 23) and treated with either: 1) Standard wound care (control); 2) UCBS; 3) AmR or 4) UCBS + AmR. Macroscopic wound closure was assessed on days 0, 3, 7, 10 and 14 post wounding. To determine the potential impact on wound recurrence, endpoint analysis was performed to determine both the overall quality of healing histologically as well as the molecular state of the wounds on day 14 via proteomic analysis. The data demonstrated the presence of both healers and non-healers. Re-epithelization took place in the healers of all treatment groups, but underlying tissue regeneration was far more pronounced following application of the combined treatment (UCBS + AmR), suggesting improved quality of healing and potentially a reduced change of recurrence long term. In non-healers, wounds failed to heal due to excessive slough formation and a reduction in LTB4 expression, suggesting impaired antimicrobial activity. Care should thus be taken since the cellular tissue product therapy could pose an increased risk for infection in some patients.
摘要：
由于微环境中复杂的多因素失调，糖尿病伤口难以愈合。需要开发新的再生方法来刺激愈合。这项研究调查了两种新型细胞组织产品的联合治疗应用，即脱细胞的富含胶原蛋白的羊膜（AmR）和富含生长因子的脐带血血清（UCBS）可以通过刺激浅层伤口闭合和伤口床再生对长期愈合结果产生积极的协同作用。在肥胖糖尿病小鼠上诱导全厚度切除伤口（B6。Cg-lepob/J,ob/ob,n=23)并用以下任一种处理:1)标准伤口护理(对照);2)UCBS;3)AmR或4)UCBS+AmR。在创伤后第0、3、7、10和14天评估宏观伤口闭合。为了确定对伤口复发的潜在影响，进行终点分析以通过蛋白质组学分析确定组织学愈合的总体质量以及第14天伤口的分子状态。数据表明存在治疗师和非治疗师。所有治疗组的治疗师都发生了上皮化，但应用联合治疗（UCBS+AmR）后，潜在组织再生明显得多，提示愈合质量改善，并可能减少长期复发的变化。在非治疗者中，伤口未能愈合，由于过度的淤泥形成和LTB4表达的减少，提示抗菌活性受损。因此应当小心,因为细胞组织产品疗法可能在一些患者中造成感染的风险增加。
