title: Functionalization of a Collagen-Hydroxyapatite Scaffold with Osteostatin to Facilitate Enhanced Bone Regeneration.
abstract: Defects within bones caused by trauma and other pathological complications may often require the use of a range of therapeutics to facilitate tissue regeneration. A number of approaches have been widely utilized for the delivery of such therapeutics via physical encapsulation or chemical immobilization suggesting significant promise in the healing of bone defects. The study focuses on the chemical immobilization of osteostatin, a pentapeptide of the parathyroid hormone (PTHrP107-111), within a collagen-hydroxyapatite scaffold. The chemical attachment method via crosslinking supports as little as 4% release of the peptide from the scaffolds after 21 d whereas non-crosslinking leads to 100% of the peptide being released by as early as 4 d. In vitro characterization demonstrates that this cross-linking method of immobilization supports a pro-osteogenic effect on osteoblasts. Most importantly, when implanted in a critical-sized calvarial defect within a rat, these scaffolds promote significantly greater new bone volume and area compared to nonfunctionalized scaffolds (**p < 0.01) and an empty defect control (***p < 0.001). Collectively, this study suggests that such an approach of chemical immobilization offers greater spatiotemporal control over growth factors and can significantly modulate tissue regeneration. Such a system may be adopted for a range of different proteins and thus offers the potential for the treatment of various complex pathologies that require localized mediation of drug delivery.
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.|Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Dublin 2, Ireland.
authors.forename: Elaine
authors.initials: E
authors.lastname: Quinlan
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.|Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Dublin 2, Ireland.
authors.forename: Emmet M
authors.initials: EM
authors.lastname: Thompson
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.|Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Dublin 2, Ireland.
authors.forename: Amos
authors.initials: A
authors.lastname: Matsiko
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.|Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Dublin 2, Ireland.
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O'Brien
authors.affiliation: Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.|Trinity Centre for Bioengineering, Trinity College Dublin, Dublin 2, Ireland.|Advanced Materials and Bioengineering Research (AMBER) Centre, RCSI & TCD, Dublin 2, Ireland.|School of Pharmacy, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
authors.forename: Adolfo
authors.initials: A
authors.lastname: López-Noriega
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects; D002460:Cell Line; D003094:Collagen / Q000737:chemistry* / Q000494:pharmacology; D017886:Durapatite / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D010006:Osteoblasts / Q000187:drug effects; D010281:Parathyroid Hormone / Q000737:chemistry / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein / Q000737:chemistry* / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; C071784:parathyroid hormone-related protein (107-111); D003094:Collagen; D017886:Durapatite
keywords: PTHrP 107-111; bone; collagen hydroxyapatite scaffolds; functionalization; tissue engineering