Systematic review: Advances of fat tissue engineering as bioactive scaffold, bioactive material, and source for adipose-derived mesenchymal stem cells in wound and scar treatment

Abstract

Fat tissue (FT) has been used for many years in regenerative surgery as a bioactive material through the lipofilling/fat graft (F-GRF)–nano-fat technique, as a bioactive scaffold when it was enriched with adipose-derived mesenchymal stem cells (AD-MSCs) contained in the stromal vascular fraction (SVF), and as a direct source of AD-MSCs used in wound healing (WH) and scar treatment (ST). This systematic review aims to describe the advances in FT engineering applied to regenerative surgery (from bench to clinic), through the use of AD-MSCs, SVF contained in F-GRF in WH and ST. The work has been performed by assessing in the selected studies autologous graft of AD-MSCs, SVF, and F-GRF compared to any control for ST and WH. The protocol was developed following the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, Clinicaltrials.gov, Scopus database, and Cochrane databases has been performed to identify papers on AD-MSCs, SVF, and F-GRF use in WH and ST in which FT was used as bioactive material–scaffold and source of AD-MSCs. Of the 714 articles initially identified, 453 articles focusing on regenerative strategies in WH and ST were selected and, consequently, only 84 articles that apparently related to AD-MSC, SVF, and F-GRF were analyzed. Of these, 61 articles identified as pre-clinical, experimental, and in vitro, and 5 articles identified as a comment and systematic review were excluded. Only 18 original articles which strictly and exclusively focused on autologous AD-MSCs, SVF, and F-GRF in ST and WH were analyzed. The included studies had to match predetermined criteria according to the PICOS (patients, intervention, comparator, outcomes, and study design) approach. The identified studies described microscopic and clinical outcomes in patients treated with AD-MSCs, SVF, and F-GRF. Collected data confirmed the safety and efficacy of FT both as bioactive material–scaffold and source of AD-MSCs in WH and ST without major side effects. Graphical abstract

Adipose-derived stromal cells increase the formation of collagens through paracrine and juxtacrine mechanisms in a fibroblast co-culture model utilizing macromolecular crowding

“…Despite advances in conventional medical treatments, there still is a need for novel regenerative strategies for improvement of wound healing, reduction of fibrosis, and stimulation of tissue regeneration in patients. ASC therapy represents one of these strategies, in which ASCs are applied alone or in combination with exogenic growth factors or scaffolds [ 43 ]. It is becoming increasingly apparent that the ECM is crucial for cell behavior and tissue function and affects various biological processes including wound healing, angiogenesis, fibrosis, and tissue regeneration [ 6 , 7 ].…”

Biomaterials as a Vital Frontier for Stem Cell-Based Tissue Regeneration

“…In a different approach, autologous fat-derived scaffold can be considered as a clinical solution for wound and scar care with better skin quality and healing time. Fat tissue can be mechanically or enzymatically processed to provide adipogenic derived stem cells suspended in fatty tissue of the stromal vascular fraction, which contains other cell types such as endothelial cells, pericytes and immune cells ( Gentile et al, 2017 ; Gentile et al, 2021 ). Similar approach was used in breast reconstruction following mastectomy instead of an implant with safe and effective clinical outcome ( Gentile et al, 2019 ).…”

New strategies in plastic surgery: autologous adipose-derived mesenchymal stem cells contained in fat grafting improves symptomatic scars

“…In the last few years, new FG preparation procedures have been developed. In fact, FG has been used both as bioactive material through the lipostructure, nano-fat and micro-fat procedures, as a bioactive scaffold when it was enhanced with SVF acting as a direct source of AD-MSCs [1]. Micro-fat and nano-fat represent new promising techniques of lipofilling, especially in the treatment of superficial skin scars [4,7].…”

“…Several procedures based on a tissue engineering approach and different cellular products have been suggested, aiming to improve wound healing (WH) and scar therapy (ST). In the field of autologous regenerative strategies, the effectiveness of autologous adipose-derived mesenchymal stem cells (AD-MSCs), contained in fat grafts (FG) has been evaluated in several fields, from facial rejuvenation to complex wound therapy [1]. The clinical improvements obtained by FG are related to AD-MSCs, contained in the stromal vascular fraction (SVF) [2], consisting of a mixture of pericytes, leukocytes, endothelial and smooth muscle cells [3].…”

“…Additionally, the FG contains several cells (AD-MSCs and adipocytes), extracellular matrix (ECM), nerves and vessels [3]. For the above-mentioned reasons, the FG may be considered both a biologically active tissue with regenerative properties when it is directly injected into the damaged tissue, and as a scaffold when it is enriched with AD-MSCs [1,2]. FGs may act as a scaffold for AD-MSCs, representing a biological matrix (cellular and extracellular) in which these cells can be incorporated and transported, resulting in improved healing time and scar signs and symptoms, via an autologous regenerative approach.…”