Background The regeneration response of the skin to mechanical stretching in vivo has been explored in reconstructive surgery to repair large-scale deformities. The ability of the skin to regenerate limits the reconstructive outcome. Here, we propose an approach in which autologous stromal vascular fraction (SVF) cells and mechanical stretching are combined to overcome this limitation and promote skin regeneration. Methods This randomized, blinded, placebo-controlled clinical trial screened 22 participants undergoing tissue expansion with exhausted regeneration. Twenty eligible participants received intradermal injections of the SVF or placebo treatments. Follow-ups were conducted at 4, 8, and 12 weeks to assess efficacy and at 2 years to assess safety. The primary endpoint was the expanded skin thickness at 12 weeks. The secondary endpoints included skin thickness at 4 and 8 weeks, the expansion index (EI), and the skin texture score at 12 weeks. Results The skin thickness of the SVF group was significantly higher than that of the control group at both 8 weeks (mean difference 0.78 [95% CI − 1.43 to − 0.11]; p = 0.018) and 12 weeks (0.65 [95% CI − 1.30 to − 0.01]; p = 0.046). In the SVF group, the increase in skin thickness was significant at 4 weeks (0.49 [95% CI − 0.80 to − 0.06]; p = 0.010) to 8 weeks (0.45 [95% CI − 0.92 to 0.02]; p = 0.026) and maintained after 12 weeks, whereas that in the control group was reduced after 8 weeks (0.42 [95% CI − 0.07 to 0.91]; p = 0.037). The SVF group showed greater EI increases than the control group (0.50 [95% CI − 0.00 to 0.99]; p = 0.047). The skin texture scores in the SVF group were greater than those in the control group at 12 weeks. Histologically, SVF-treated expanded skin showed more proliferating cells and blood vessels, and the extracellular matrix volume increased. No severe adverse events occurred. Conclusions Transplantation of SVF cells can expedite the potency of mechanical stretch-induced skin regeneration and provide clinical reconstruction with plentiful tissue. Trial registration This trial was registered with the Chinese Clinical Trial Registry, ChiCTR2000039317 (registered 23 October 2020—retrospectively registered).

Background: The regeneration response of skin to mechanical stretching in vivo has been explored in reconstructive surgery for repairing large-scale deformities. The ability of skin to regenerate limits the reconstructive outcome. Here, we propose an approach in which autologous adipose-derived stem cells and mechanical stretching are combined to overcome this limitation and promote skin regeneration.Methods: This randomized, blinded, placebo-controlled clinical trial screened 22 participants undergoing tissue expansion with a presence of exhausted regeneration. Twenty eligible participants received intradermal injections with stromal vascular fraction (SVF) or placebo treatments. Follow-ups were conducted at 4, 8, and 12-weeks to assess efficacy and for 2-years to assess safety. The primary endpoint was the expanded skin thickness at 12 weeks. The secondary endpoints included the skin thickness at 4 and 8 weeks, the expansion index (EI) and the skin texture score at all visits. Results: The skin thickness of the SVF group was significantly higher than that of the control group at both 8 weeks (mean difference 0.78 [95% CI -1.43 to -0.11]; p = 0.018) and 12 weeks(0.65 [95% CI -1.30 to -0.01]; p = 0.046). In the SVF group, the increment of skin thickness was significant at 4 weeks (0.49 [95% CI -0.80 to -0.06]; p = 0.010) to 8 weeks (0.45 [95% CI -0.92 to 0.02]; p = 0.026) and maintained after 12 weeks, whereas that in the control group was reduced after 8 weeks (0.42 [95% CI -0.07 to 0.91]; p = 0.037). The SVF group showed higher EI increments than the control group (0.50 [95% CI -0.00 to 0.99]; p = 0.047). The skin texture scores in the SVF group were higher than those in the control group at 12 weeks. Histologically, the SVF-treated expanded skin showed more proliferating cells and blood vessels, and the volume of extracellular matrix increased. No severe adverse events occurred.Conclusions: Transplantation of autologous adipose-derived stem cells can expedite the potency of mechanical stretch-induced skin regeneration and provide clinical reconstruction with plentiful tissue. Trial registration: This trial was registered with Chinese Clinical Trial, ChiCTR2000039317 (registered 23 Oct 2020 - retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=62738).