A collagen–hydroxyapatite scaffold allows for binding and co-delivery of recombinant bone morphogenetic proteins and bisphosphonates

• Published in: Acta biomaterialia Vol. 10; no. 5; pp. 2250 - 2258
• Main Authors: Murphy, Ciara M., Schindeler, Aaron, Gleeson, John P., Yu, Nicole Y.C., Cantrill, Laurence C., Mikulec, Kathy, Peacock, Lauren, O’Brien, Fergal J., Little, David G.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2014
• Subjects: Acid Phosphatase - metabolism; Animals; Bisphosphonate; Bone and Bones - diagnostic imaging; Bone and Bones - drug effects; Bone Morphogenetic Proteins - pharmacology; Cell Death - drug effects; Collagen; Collagen - chemistry; Diphosphonates - pharmacology; Drug Delivery Systems; Durapatite - chemistry; Fluorescent Dyes - metabolism; Humans; Hydroxyapatite; Isoenzymes - metabolism; Male; Mice; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteogenesis - drug effects; Porosity; Prosthesis Implantation; Rats; Rats, Wistar; Recombinant Proteins - pharmacology; rhBMP-2; Tartrate-Resistant Acid Phosphatase; Tissue Scaffolds; X-Ray Microtomography; Zoledronic acid; rhBMP-2; Zoledronic acid; Bisphosphonate; Hydroxyapatite; Collagen
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2014.01.016

In vitro assays confirmed delayed release of both rhBMP-2 and ZA from CHA scaffolds. In vivo, CHA scaffold delivery of rhBMP-2/ZA increased bone volume in an ectopic muscle pouch model. [Display omitted] 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 14C-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.