Tresoldi Marco Mario, Graziano Antonio, Malovini Alberto, Faga Angela, Nicoletti Giovanni
Plastic and Reconstructive Surgery, Department of Clinical Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Viale Brambilla, 74 Pavia, Italy.
Plastic and Reconstructive Surgery Unit, Department of Surgery, Istituti Clinici Scientifici Maugeri, Via Salvatore Maugeri, 10 Pavia, Italy.
Stem Cells Int. 2019 Sep 8;2019:9843407. doi: 10.1155/2019/9843407. eCollection 2019.
The aim of the study was the objective assessment of the effectiveness of a microfragmented dermal extract obtained with Rigenera™ technology in promoting the wound healing process in an homogeneous experimental human acute surgical wound model. The study included 20 patients with 24 acute postsurgical soft tissue loss and a planned sequential two-stage repair with a dermal substitute and an autologous split-thickness skin graft. Each acute postsurgical soft tissue loss was randomized to be treated either with an Integra® dermal substitute enriched with the autologous dermal micrografts obtained with Rigenera™ technology (group A-Rigenera™ protocol) or with an Integra® dermal substitute only (group B-control). The reepithelialization rate in the wounds was assessed in both groups at 4 weeks through digital photography with the software "ImageJ." The dermal cell suspension enrichment with the Rigenera™ technology was considered effective if the reepithelialized area was higher than 25% of the total wound surface as this threshold was considered far beyond the expected spontaneous reepithelialization rate. In the Rigenera™ protocol group, the statistical analysis failed to demonstrate any significant difference vs. the controls. The old age of the patients likely influenced the outcome as the stem cell regenerative potential is reduced in the elderly. A further explanation for the unsatisfying results of our trial might be the inadequate amount of dermal stem cells used to enrich the dermal substitutes. In our study, we used a 1 : 200 donor/recipient site ratio to minimize donor site morbidity. The gross dimensional disparity between the donor and recipient sites and the low concentration of dermal mesenchymal stromal stem cells might explain the poor epithelial proliferative boost observed in our study. A potential option in the future might be preconditioning of the dermal stem cell harvest with senolytic active principles that would fully enhance their regenerative potential. This trial is registered with trial protocol number NCT03912675.
本研究的目的是在同质的实验性人类急性手术伤口模型中，客观评估采用Rigenera™技术获得的微片段真皮提取物在促进伤口愈合过程中的有效性。该研究纳入了20例患者，他们共有24处急性术后软组织缺损，并计划采用真皮替代物和自体中厚皮片进行序贯两阶段修复。每处急性术后软组织缺损均被随机分配，分别采用富含通过Rigenera™技术获得的自体真皮微移植物的Integra®真皮替代物进行治疗（A组 - Rigenera™方案），或仅采用Integra®真皮替代物进行治疗（B组 - 对照组）。两组均在4周时通过使用“ImageJ”软件进行数码摄影来评估伤口的再上皮化率。如果再上皮化面积高于伤口总面积的25%，则认为采用Rigenera™技术进行的真皮细胞悬液富集是有效的，因为该阈值被认为远高于预期的自发再上皮化率。在Rigenera™方案组中，统计分析未能显示与对照组有任何显著差异。患者的高龄可能影响了结果，因为老年人的干细胞再生潜力会降低。我们试验结果不尽人意的另一个解释可能是用于富集真皮替代物的真皮干细胞数量不足。在我们的研究中，我们采用1∶200的供体/受体部位比例以尽量减少供体部位的发病率。供体和受体部位之间的总体尺寸差异以及真皮间充质基质干细胞的低浓度可能解释了我们研究中观察到的上皮增殖促进效果不佳的情况。未来的一个潜在选择可能是用具有衰老细胞溶解活性成分对真皮干细胞采集进行预处理，这将充分增强其再生潜力。本试验已在试验方案编号NCT03912675下注册。
