Engineered skin graft with stromal vascular fraction cells encapsulated in fibrin–collagen hydrogel: A clinical study for diabetic wound healing

Abstract

Despite the abundance of skin substitutes in the worldwide market, major hurdles in developing more complex tissues include the addition of skin appendages and vascular networks as the most important structure. The aim of this research was a clinical feasibility study of a novel prevascularized skin grafts containing the dermal and epidermal layer using the adipose stromal vascular fraction (SVF)‐derived endothelial cell population for vascular network regeneration. Herein, we characterized hydrogel with emphasis on biological compatibility and cell proliferation, migration, and vitality. The therapeutic potential of the prevascularized hydrogel transplanted on five human subjects as an intervention group with diabetic wounds was compared with nonvascularized skin grafts as the control on five patients. Wound planimetric and biometric analysis was performed using a Mann–Whitney nonparametric t‐test (p ≤ .05). The fibrin–collagen hydrogel was suitable for skin organotypic cell culture. There was a significant (p ≤ .05) increased in skin thickness and density in the vascular beds of the hypodermis measured with skin scanner compared with that in the control group. No significant macroscopic differences were observed between the intervention and control groups (p ≤ .05). In summary, we report for the first time the use of autologous dermal–epidermal skin grafts with intrinsic vascular plexus in a clinical feasibility study. The preliminary data showed that SVF‐based full‐thickness skin grafts are safe and accelerate the wound healing process. The next stage of the study is a full‐scale randomized clinical trial for the treatment of patients with chronic wounds.

Efficacy of allogeneic cord blood platelet gel on wounds of dystrophic epidermolysis bullosa patients after pseudosyndactyly surgery

“…In the current study, the appropriate volume and concentration of thrombin were used according to the final volume and concentration of platelet concentrate as well as calcium gluconate; therefore, the formation fibrin network and platelet gel had a suitable density since if the fibrin network has high density and hard structure, the growth factors derived from cord blood platelet do not have a proper release and spread in surface wound area and are trapped in the fibrin network itself and wound healing does not have a good quality. Also, if the concentration and volume of thrombin used are low, the platelet gel is very loose and cannot be adjusted at the wound site 23,29,30 …”

“…Platelets are a great source of growth factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor (TGF), and platelet‐derived growth factor (PDGF), all of which play an important role in wound healing, tissue regeneration, and generally in the fields of regenerative medicine. Platelet‐rich plasma of the umbilical cord blood contains a high level of PDGF, which is an important factor in restoration and regeneration of the damaged tissue 20‐23 . This method (preparation of cord blood platelet gel) was studied and evaluated for the first time in Italy 24…”

Bioengineered Skin Substitutes: Advances and Future Trends

“…In a pilot study, we overcame these hurdles by the in vitro generation of capillary networks in DESSs using endothelial and mesenchymal progenitors derived from the stromal vascular fraction (SVF) of human adipose tissue (Figure 2) [12,13,20]. This approach holds great promise for future clinical applications as adipose tissue represents a convenient, abundant, and easily accessible cell source [78]. Moreover, this concept was previously successfully used in the engineering of precisely sized osteogenic constructs, increasing the efficiency and uniformity of bone tissue formation [79].…”

Clinical Translational Potential in Skin Wound Regeneration for Adipose-Derived, Blood-Derived, and Cellulose Materials: Cells, Exosomes, and Hydrogels

“…Further studies have demonstrated the ability of ASCs to modulate mixed lymphocyte reactions in vitro and to display immunosuppressive properties in vivo [ 37 , 38 ]. Through the use of enzymatic isolation methods, independent laboratories have advanced SVF cell and ASC production as current good manufacturing practices (cGMP) to create clinical-grade cell products that are suitable for the treatment of skin wounds, soft tissue cosmesis, or bone defects [ 39 , 40 , 41 , 42 ]. These approaches have relied on the use of the patient’s autologous serum or the use of human platelet lysates for cell culture and expansion [ 43 , 44 ].…”