Skin substitutes with noncultured autologous skin cell suspension heal porcine full‐thickness wounds in a one‐stage procedure

Abstract

Clinical application of skin substitute is typically a two‐stage procedure with application of skin substitute matrix to the wound followed by engraftment of a split‐thickness skin graft (STSG). This two‐stage procedure requires multiple interventions, increasing the time until the wound is epithelialised. In this study, the feasibility of a one‐stage procedure by combining bioengineered collagen‐chondroitin‐6‐sulfate (DS1) or decellularised fetal bovine skin substitute (DS2) with autologous skin cell suspension (ASCS) in a porcine full‐thickness wound healing model was evaluated. Twelve full‐thickness excisional wounds on the backs of pigs received one of six different treatments: empty; ASCS; DS1 with or without ASCS; DS2 with or without ASCS. The ASCS was prepared using a point‐of‐care device and was seeded onto the bottom side of DS1, DS2, and empty wounds at 80 000 cells/cm2. Wound measurements and photographs were taken on days 0, 9, 14, 21, 28, 35, and 42 post‐wounding. Histological analysis was performed on samples obtained on days 9, 14, 28, and 42. Wounds in the empty group or with ASCS alone showed increased wound contraction, fibrosis, and myofibroblast density compared with other treatment groups. The addition of ASCS to DS1 or DS2 resulted in a marked increase in re‐epithelialisation of wounds at 14 days, from 15 ± 11% to 71 ± 20% (DS1 vs DS1 + ASCS) or 28 ± 14% to 77 ± 26 (DS2 vs DS2 + ASCS) despite different mechanisms of tissue regeneration employed by the DS used. These results suggest that this approach may be a viable one‐stage treatment in clinical practice.

Point of care approaches to 3D bioprinting for wound healing applications

“…The ability of FB and KC cells to self-assemble into distinct dermal and epidermal layers in-vivo in response to endogenous biological cues was observed over 21 d. This migration was corroborated by previous works where cultured KCs seeded onto the underside of a skin substitute were observed to migrate upwards through the dermal scaffold to form an epidermis in 2-3 weeks [82,83]. In a similar study conducted more recently, Damaraju et al [27] applied drops of ReCell™ to the underside of a skin substitute used to treat full-thickness porcine wounds. Epithelial hyperplasia (the presence of KCs migrating upwards through the dermis towards the epidermis) was resolved by 42 d and the union of products was again deemed promising as a POC treatment strategy.…”

“…Gaining significant traction in the clinic, ReCell™ (Avita Medical Ltd, Cambridge, England) is an autologous cell harvesting, processing and delivery device that involves spraying non-cultured epidermal cells onto a wound site as soon as 30 min from biopsy harvesting [25]. Although not indicated for the treatment of full-thickness wounds in its standalone form, in-vivo studies showed that when ReCell™ was combined with Integra ® , the self-organisation of autologous cells accelerated re-epithelialisation of full-thickness wounds and mitigated the need for a STSG procedure [26,27]. To date, this integration of products is perhaps nearest to the vision of an immediate, single-stage, graft-free treatment strategy for full-thickness wounds.…”

Bioengineered skin constructs based on mesenchymal stromal cells and acellular dermal matrix exposed to inflammatory microenvironment releasing growth factors involved in skin repair

“…Our results reported more significant signs of repair than those reported in a study on the same biomodel using decellularized fetal bovine skin substitute with autologous skin cell suspension [ 69 ], indicating that the wound closed in approximately 42 days after treatment and according to the histological result, the immature epithelium and presence of inflammatory cells in the wound treated with decellularized skin substitute were observed at 28 days. Likewise, the skin repair potential of construct 1 and hADM described here was higher than similar strategies evaluated in different animal models [ 67 , 70 , 71 ].…”