title: Polyglutamate directed coupling of bioactive peptides for the delivery of osteoinductive signals on allograft bone.
abstract: Allograft bone is commonly used as an alternative to autograft, however allograft lacks many osteoinductive factors present in autologous bone due to processing. In this study, we investigated a method to reconstitute allograft with osteoregenerative factors. Specifically, an osteoinductive peptide from collagen I, DGEA, was engineered to express a heptaglutamate (E7) domain, which binds the hydroxyapatite within bone mineral. Addition of E7 to DGEA resulted in 9× greater peptide loading on allograft, and significantly greater retention after a 5-day interval with extensive washing. When factoring together greater initial loading and retention, the E7 domain directed a 45-fold enhancement of peptide density on the allograft surface. Peptide-coated allograft was also implanted subcutaneously into rats and it was found that E7DGEA was retained in vivo for at least 3 months. Interestingly, E7DGEA peptides injected intravenously accumulated within bone tissue, implicating a potential role for E7 domains in drug delivery to bone. Finally, we determined that, as with DGEA, the E7 modification enhanced coupling of a bioactive BMP2-derived peptide on allograft. These results suggest that E7 domains are useful for coupling many types of bone-regenerative molecules to the surface of allograft to reintroduce osteoinductive signals and potentially advance allograft treatments.
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Bonnie K
authors.initials: BK
authors.lastname: Culpepper
authors.forename: Paul P
authors.initials: PP
authors.lastname: Bonvallet
authors.forename: Michael S
authors.initials: MS
authors.lastname: Reddy
authors.forename: Selvarangan
authors.initials: S
authors.lastname: Ponnazhagan
authors.forename: Susan L
authors.initials: SL
authors.lastname: Bellis
mesh_terms: D000818:Animals; D001846:Bone Development / Q000187:drug effects / Q000502:physiology*; D016025:Bone Transplantation / Q000379:methods*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009842:Oligopeptides; C113781:aspartyl-glycyl-glutamyl-alanine; D018698:Glutamic Acid