A collagen-hydroxyapatite scaffold allows for binding and co-delivery of recombinant bone morphogenetic proteins and bisphosphonates.
An emerging paradigm in orthopedics is that a bone-healing outcome is the product of the anabolic (bone-forming) and catabolic (bone-resorbing) outcomes. Recently, surgical and tissue engineering strategies have emerged that combine recombinant human bone morphogenetic proteins (rhBMPs) and bisphosphonates (BPs) in order to maximize anabolism and minimize catabolism. Collagen-based scaffolds that are the current surgical standard can bind rhBMPs, but not BPs. We hypothesized that a biomimetic collagen-hydroxyapatite (CHA) scaffold would bind both agents and produce superior in vivo outcomes. Consistent with this concept, in vitro elution studies utilizing rhBMP-2 ELISA assays and scintillation counting of (14)C-radiolabeled zoledronic acid (ZA) confirmed delayed release of both agents from the CHA scaffold. Next, scaffolds were tested for their capacity to form ectopic bone after surgical implantation into the rat hind limb. Using CHA, a significant 6-fold increase in bone volume was seen in rhBMP-2/ZA groups compared to rhBMP-2 alone, confirming the ability of ZA to enhance rhBMP-2 bone formation. CHA scaffolds were found to be capable of generating mineralized tissue in the absence of rhBMP-2. This study has implications for future clinical treatments of critical bone defects. It demonstrates the relative advantages of co-delivering anabolic and anti-catabolic agents using a multicomponent scaffold system.
Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Sydney, NSW, Australia; Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia. Electronic address: ciara.murphy@sydney.edu.au.
Ciara M
CM
Murphy
Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Sydney, NSW, Australia; Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia.
Aaron
A
Schindeler
Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland.
John P
JP
Gleeson
Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Sydney, NSW, Australia; Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia.
Nicole Y C
NY
Yu
Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Sydney, NSW, Australia; Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia.
Laurence C
LC
Cantrill
Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Sydney, NSW, Australia.
Kathy
K
Mikulec
Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Sydney, NSW, Australia.
Lauren
L
Peacock
Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, Dublin, Ireland; Trinity Centre for Bioengineering, Trinity College, Dublin, Ireland; Advanced Materials and BioEngineering Research Centre (AMBER), RCSI & TCD, Dublin, Ireland.
Fergal J
FJ
O'Brien
Orthopaedic Research & Biotechnology Unit, The Children's Hospital at Westmead, Sydney, NSW, Australia; Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, NSW, Australia.
David G
DG
Little
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003094:Collagen / Q000737:chemistry*; D004164:Diphosphonates / Q000494:pharmacology*; D016503:Drug Delivery Systems; D017886:Durapatite / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D016062:Porosity; D019919:Prosthesis Implantation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology*; D000071681:Tartrate-Resistant Acid Phosphatase; D054457:Tissue Scaffolds; D055114:X-Ray Microtomography
D019485:Bone Morphogenetic Proteins; D004164:Diphosphonates; D005456:Fluorescent Dyes; D007527:Isoenzymes; D011994:Recombinant Proteins; D003094:Collagen; D017886:Durapatite; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase
Bisphosphonate; Collagen; Hydroxyapatite; Zoledronic acid; rhBMP-2