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-beta 1 and alpha-SMA together with an increase of TGF-beta 3, 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. (C) 2015 Acta Materialia Inc. Published by Elsevier B.V. All rights reserved.Univ Fed Minas Gerais, Inst Biol Sci, Dept Biochem & Immunol, BR-31270901 Belo Horizonte, MG, BrazilUniv Minho, Headquarters European Inst Excellence Tissue Engn, Res Grp Biomat Biodegradables & Biomimet 3Bs, P-4806909 Taipas, Guimaraes, PortugalPT Govt Associate Lab, ICVS 3Bs, Braga, PortugalUniv Fed Minas Gerais, Inst Biol Sci, Dept Morphol, BR-31270901 Belo Horizonte, MG, BrazilFed Univ Espirito Santos, Dept Vet Med, BR-29500000 Alegre, ES, BrazilUniversidade Federal de São Paulo, Dept Nephrol, BR-04023900 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Nephrol, BR-04023900 São Paulo, SP, BrazilWeb of ScienceConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)CNPq: 141775/2010-6/141787/2012CNPq: 564779/2010-5CNPq: 490414/2010-9CAPES: PDEE0046/11-