title: Polyhydroxybutyrate-co-hydroxyvalerate structures loaded with adipose stem cells promote skin healing with reduced scarring.
abstract: Currently available skin substitutes are still associated with a range of problems including poor engraftment resulting from deficient vascularization, and excessive scar formation, among others. Trying to overcome these issues, this work proposes the combination of poly(3-hydroxybutyrate-co-hydroxyvalerate) (PHBV) structures with adipose-derived stem cells (ASCs) to offer biomechanical and biochemical signaling cues necessary to improve wound healing in a full-thickness model. PHBV scaffold maintained the wound moisture and demonstrated enough mechanical properties to withstand wound contraction. Also, exudate and inflammatory cell infiltration enhanced the degradation of the structure, and thus healing progression. After 28 days all the wounds were closed and the PHBV scaffold was completely degraded. The transplanted ASCs were detected in the wound area only at day 7, correlating with an up-regulation of VEGF and bFGF at this time point that consequently led to a significant higher vessel density in the group that received the PHBV loaded with ASCs. Subsequently, the dermis formed in the presence of the PHBV loaded with ASCs possesses a more complex collagen structure. Additionally, an anti-scarring effect was observed in the presence of the PHBV scaffold indicated by a down-regulation of TGF-β1 and α-SMA together with an increase of TGF-β3, when associated with ASCs. These results indicate that although PHBV scaffold was able to guide the wound healing process with reduced scarring, the presence of ASCs was crucial to enhance vascularization and provide a better quality neo-skin. Therefore, we can conclude that PHBV loaded with ASCs possesses the necessary bioactive cues to improve wound healing with reduced scarring.
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Caixa Postal 486, CEP 31.270-901 Belo Horizonte, Minas Gerais, Brazil; 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal. Electronic address: alessandrazonari@gmail.com.
authors: Alessandra
authors: A
authors: Zonari
authors: Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Caixa Postal 486, CEP 31.270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Thaís M M
authors: TM
authors: Martins
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Caixa Postal 486, CEP 31.270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Ana Cláudia C
authors: AC
authors: Paula
authors: Department of Veterinary Medicine, Federal University of Espírito Santos, Caixa Postal 16, CEP 29500-000 Alegre, Espírito Santo, Brazil.
authors: Jankerle N
authors: JN
authors: Boeloni
authors: Department of Nephrology, Federal University of São Paulo, CEP 04.023-900 São Paulo, SP, Brazil.
authors: Silviene
authors: S
authors: Novikoff
authors: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors: Alexandra P
authors: AP
authors: Marques
authors: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors: Vitor M
authors: VM
authors: Correlo
authors: 3B's Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, 4806-909 Taipas, Guimarães, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors: Rui L
authors: RL
authors: Reis
authors: Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Caixa Postal 486, CEP 31.270-901 Belo Horizonte, Minas Gerais, Brazil.
authors: Alfredo M
authors: AM
authors: Goes
mesh_terms: D000199:Actins / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D030801:Animals, Genetically Modified; D001696:Biomechanical Phenomena; D002454:Cell Differentiation; D002921:Cicatrix / Q000473:pathology* / Q000517:prevention & control*; D018450:Disease Progression; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008297:Male; D010641:Phenotype; D011091:Polyesters / Q000737:chemistry*; D051381:Rats; D011917:Rats, Inbred Lew; D015398:Signal Transduction; D017768:Skin, Artificial; D013234:Stem Cells / Q000166:cytology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing; D000094122:Polyhydroxybutyrates
chemical_list: D000199:Actins; D016222:Fibroblast Growth Factor 2; D011091:Polyesters; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D042461:Vascular Endothelial Growth Factor A; C052620:poly(3-hydroxybutyrate)-co-(3-hydroxyvalerate); D000094122:Polyhydroxybutyrates
keywords: Myofibroblasts; Paracrine signaling; Scar; Tissue engineering; Wound healing