Multilayer Nanoscale Encapsulation of Biofunctional Peptides to Enhance Bone Tissue Regeneration In Vivo. Issue 8 (7th February 2017)

• Record Type: Journal Article
• Authors: Gentile, Piergiorgio; Ferreira, Ana Marina; Callaghan, Jill T.; Miller, Cheryl A.; Atkinson, Joss; Freeman, Christine; Hatton, Paul V.
• Is Part Of: Advanced healthcare materials. Volume 6:Issue 8(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-02-07
• Subjects: bone regeneration -- electrospinning -- layer‐by‐layer -- nanoencapsulation -- osteoinductive peptides; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201601182
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract : Bone tissue healing is a dynamic process that is initiated by the recruitment of osteoprogenitor cells followed by their migration, proliferation, differentiation, and development of a mineralizing extracellular matrix. The work aims to manufacture a functionalized porous membrane that stimulates early events in bone healing for initiating a regenerative cascade. Layer‐by‐layer (LbL) assembly is proposed to modify the surface of osteoconductive electrospun meshes, based on poly(lactic‐co‐glycolic acid) and nanohydroxyapatite, by using poly(allylamine hydrochloride) and poly(sodium 4‐styrenesulfonate) as polyelectrolytes. Molecular cues are incorporated by grafting peptide fragments into the discrete nanolayers. KRSR (lysine‐arginine‐serine‐arginine) sequence is grafted to enhance cell adhesion and proliferation, NSPVNSKIPKACCVPTELSAI to guide bone marrow mesenchymal stem cells differentiation in osteoblasts, and FHRRIKA (phenylalanine‐histidine‐arginine‐arginine‐isoleucine‐lysine‐alanine) to improve mineralization matrix formation. Scanning electron microscopy, infrared spectroscopy, and X‐ray photoelectron spectroscopy demonstrate the successful surface functionalization. Furthermore, the peptide incorporation enhances cellular processes, with good viability and significant increase of alkaline phosphatase activity, osteopontin, and osteocalcin. The functionalized membrane induces a favorable in vivo response after implantation for four weeks in nonhealing rat calvarial defect model. It is concluded that the multilayer nanoencapsulation of biofunctional peptides using LbL approach has significant potential as innovative manufacturing technique to improve bone regeneration in orthopedic and craniofacial medical devices. Abstract : Layer‐by‐layer assembly is a powerful tool to modify the surface of biomedical devices for imparting enhanced biological properties. This work proposes an in vitro model for mimicking the bone healing process, by grafting appropriate bone peptide sequences to the discrete nanolayers for improving the mesenchymal stem cell adhesion, proliferation, and differentiation, and the formation of mineralization matrix.