An Elastin‐Derived Composite Matrix for Enhanced Vascularized and Innervated Bone Tissue Reconstruction: From Material Development to Preclinical Evaluation

Author:

Mahmoudi Nadia1ORCID,Roque Micaela1,Paiva Dos Santos Bruno1ORCID,Oliveira Hugo1ORCID,Siadous Robin1ORCID,Rey Sylvie1,Garanger Elisabeth2ORCID,Lecommandoux Sébastien2ORCID,Catros Sylvain3ORCID,Garbay Bertrand2ORCID,Amédée Vilamitjana Joëlle1ORCID

Affiliation:

1. Tissue Bioengineering Laboratory (BioTis) Inserm U1026 University of Bordeaux Bordeaux France

2. Univ. Bordeaux CNRS Bordeaux INP, LCPO UMR Pessac 5629 France

3. CHU Bordeaux Dentistry and Oral Health Department Bordeaux 33076 France

Abstract

AbstractDespite progress in bone tissue engineering, reconstruction of large bone defects remains an important clinical challenge. Here, a biomaterial designed to recruit bone cells, endothelial cells, and neuronal fibers within the same matrix is developed, enabling bone tissue regeneration. The bioactive matrix is based on modified elastin‐like polypeptides (ELPs) grafted with laminin‐derived adhesion peptides IKVAV and YIGSR, and the SNA15 peptide for retention of hydroxyapatite (HA) particles. The composite matrix shows suitable porosity, interconnectivity, biocompatibility for endothelial cells, and the ability to support neurites outgrowth by sensory neurons. Subcutaneous implantation leads to the formation of osteoid tissue, characterized by the presence of bone cells, vascular networks, and neuronal structures, while minimizing inflammation. Using a rat femoral condyle defect model, longitudinal micro‐CT analysis is performed, which demonstrates a significant increase in the volume of mineralized tissue when using the ELP‐based matrix compared to empty defects and a commercially available control (Collapat). Furthermore, visible blood vessel networks and nerve fibers are observed within the lesions after a period of two weeks. By incorporating multiple key components that support cell growth, mineralization, and tissue integration, this ELP‐based composite matrix provides a holistic and versatile solution to enhance bone tissue regeneration.

Funder

Société d'Accélération du Transfert de Technologies

Publisher

Wiley

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