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Development of a cell-free and growth factor-free hydrogel capable of inducing angiogenesis and innervation after subcutaneous implantation

hal.structure.identifierBioingénierie tissulaire [BIOTIS]
dc.contributor.authorDOS SANTOS, Bruno Paiva
hal.structure.identifierLaboratoire de Chimie des Polymères Organiques [LCPO]
dc.contributor.authorGARBAY, Bertrand
ORCID: 0000-0001-5756-2627
IDREF: 033777551
hal.structure.identifierBioingénierie tissulaire [BIOTIS]
dc.contributor.authorFENELON, Mathilde
hal.structure.identifierLaboratoire de Chimie des Polymères Organiques [LCPO]
dc.contributor.authorROSSELIN, Marie
hal.structure.identifierLaboratoire de Chimie des Polymères Organiques [LCPO]
dc.contributor.authorGARANGER, Elisabeth
hal.structure.identifierLaboratoire de Chimie des Polymères Organiques [LCPO]
dc.contributor.authorLECOMMANDOUX, Sebastien
hal.structure.identifierBioingénierie tissulaire [BIOTIS]
dc.contributor.authorOLIVEIRA, Hugo
hal.structure.identifierBioingénierie tissulaire [BIOTIS]
dc.contributor.authorAMÉDÉE, Joëlle
dc.date.accessioned2021-06-10T07:04:19Z
dc.date.available2021-06-10T07:04:19Z
dc.date.issued2019-11
dc.identifier.issn1742-7061
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/78966
dc.description.abstractEnDespite significant progress in the field of biomaterials for bone repair, the lack of attention to the vascular and nervous networks within bone implants could be one of the main reasons for the delayed or impaired recovery of bone defects. The design of innovative biomaterials should improve the host capacity of healing to restore a functional tissue, taking into account that the nerve systems closely interact with blood vessels in the bone tissue. The aim of this work is to develop a cell-free and growth factor-free hydrogel capable to promote angiogenesis and innervation. To this end, we have used elastin-like polypeptides (ELPs), poly(ethylene glycol) (PEG) and increasing concentrations of the adhesion peptide IKVAV (25% (w/w) representing 1.7 mM and 50% (w/w) representing 4.1 mM) to formulate and produce hydrogels. When characterized in vitro, hydrogels have fine-tunable rheological properties, microporous structure and are biocompatible. At the biological level, 50% IKVAV composition up-regulated Runx2, Osx, Spp1, Vegfa and Bmp2 in mesenchymal stromal cells and Tek in endothelial cells, and sustained the formation of long neurites in sensory neurons. When implanted subcutaneously in mice, hydrogels induced no signals of major inflammation and the 50% IKVAV composition induced higher vessel density and formation of nervous terminations in the peripheral tissue. This novel composite has important features for tissue engineering, showing higher osteogenic, angiogenic and innervation potential in vitro, being not inflammatory in vivo, and inducing angiogenesis and innervation subcutaneously. STATEMENT OF SIGNIFICANCE: One of the main limitations in the field of tissue engineering remains the sufficient vascularization and innervation during tissue repair. In this scope, the development of advanced biomaterials that can support these processes is of crucial importance. Here, we formulated different compositions of Elastin-like polypeptide-based hydrogels bearing the IKVAV adhesion sequence. These compositions showed controlled mechanical properties, and were degradable in vitro. Additionally, we could identify in vitro a composition capable to promote neurite formation and to modulate endothelial and mesenchymal stromal cells gene expression, in view of angiogenesis and osteogenesis, respectively. When tested in vivo, it showed no signs of major inflammation and induced the formation of a highly vascularized and innervated neotissue. In this sense, our approach represents a potential advance in the development of new strategies to promote tissue regeneration, taking into account both angiogenesis and innervation.
dc.language.isoen
dc.publisherElsevier
dc.subject.enElastin-like polypeptide
dc.subject.enIKVAV
dc.subject.enNeurite outgrowth
dc.subject.enOsteogenesis
dc.subject.enSensory neurons
dc.title.enDevelopment of a cell-free and growth factor-free hydrogel capable of inducing angiogenesis and innervation after subcutaneous implantation
dc.typeArticle de revue
dc.identifier.doi10.1016/j.actbio.2019.08.028
dc.subject.halSciences du Vivant [q-bio]/Ingénierie biomédicale/Biomatériaux
bordeaux.journalActa Biomaterialia
bordeaux.page154-167
bordeaux.volume99
bordeaux.hal.laboratoriesBioingénierie Tissulaire (BioTis) - U1026*
bordeaux.institutionCNRS
bordeaux.institutionINSERM
bordeaux.institutionCHU de Bordeaux
bordeaux.institutionInstitut Bergonié
bordeaux.peerReviewedoui
hal.identifierinserm-02863407
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//inserm-02863407v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Acta%20Biomaterialia&rft.date=2019-11&rft.volume=99&rft.spage=154-167&rft.epage=154-167&rft.eissn=1742-7061&rft.issn=1742-7061&rft.au=DOS%20SANTOS,%20Bruno%20Paiva&GARBAY,%20Bertrand&FENELON,%20Mathilde&ROSSELIN,%20Marie&GARANGER,%20Elisabeth&rft.genre=article


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