Multilayer Nanoscale Encapsulation of Biofunctional Peptides to Enhance Bone Tissue Regeneration In Vivo.
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.
School of Mechanical and Systems Engineering, Newcastle University, Claremont Road, Newcastle upon Tyne, NE1 7RU, UK.
Piergiorgio
P
Gentile
School of Mechanical and Systems Engineering, Newcastle University, Claremont Road, Newcastle upon Tyne, NE1 7RU, UK.
Ana Marina
AM
Ferreira
School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, Sheffield, S10 2TA, UK.
Jill T
JT
Callaghan
School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, Sheffield, S10 2TA, UK.
Cheryl A
CA
Miller
School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, Sheffield, S10 2TA, UK.
Joss
J
Atkinson
School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, Sheffield, S10 2TA, UK.
Christine
C
Freeman
School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, Sheffield, S10 2TA, UK.
Paul V
PV
Hatton
D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D017886:Durapatite / Q000737:chemistry / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D053769:Nanocapsules / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology
D053769:Nanocapsules; D009842:Oligopeptides; D011108:Polymers; D013451:Sulfonic Acids; C437191:lysyl-arginyl-seryl-arginine; C546710:phenylalanyl-histidyl-arginyl-arginyl-isoleucyl-lysyl-alanine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017886:Durapatite; C077114:styrenesulfonic acid polymer
bone regeneration; electrospinning; layer-by-layer; nanoencapsulation; osteoinductive peptides