Repair of Osteochondral Defects in a Rabbit Model Using a Porous Hydroxyapatite Collagen Composite Impregnated With Bone Morphogenetic Protein‐2

Abstract

Articular cartilage has a limited capacity for spontaneous repair, and an effective method to repair damaged articular cartilage has not yet been established. The purpose of this study was to evaluate the effect of transplantation of porous hydroxyapatite collagen (HAp/Col) impregnated with bone morphogenetic protein‐2 (BMP‐2). To evaluate the characteristics of porous HAp/Col as a drug delivery carrier of recombinant human BMP‐2 (rhBMP‐2), the rhBMP‐2 adsorption capacity and release kinetics of porous HAp/Col were analyzed. Porous HAp/Col impregnated with different amounts of rhBMP‐2 (0, 5, and 25 μg) was implanted into osteochondral defects generated in the patellar groove of Japanese white rabbits to evaluate the effect on osteochondral defect regeneration. At 3, 6, 12, and 24 weeks after operation, samples were harvested and subjected to micro‐computed tomography analysis and histological evaluation of articular cartilage and subchondral bone repair. The adsorption capacity was 329.4 μg of rhBMP‐2 per cm3 of porous HAp/Col. Although 36% of rhBMP‐2 was released within 24 h, more than 50% of the rhBMP‐2 was retained in the porous HAp/Col through the course of the experiment. Defects treated with 5 μg of rhBMP‐2 showed the most extensive subchondral bone repair and the highest histological regeneration score, and differences against the untreated defect group were significant. The histological regeneration score of defects treated with 25 μg of rhBMP‐2 increased up to 6 weeks after implantation, but then decreased. Porous HAp/Col, therefore, is an appropriate carrier for rhBMP‐2. Implantation of porous HAp/Col impregnated with rhBMP‐2 is effective for rigid subchondral bone repair, which is important for the repair of the smooth articular surface.

Augmentation of fracture healing by hydroxyapatite/collagen paste and bone morphogenetic protein‐2 evaluated using a rat femur osteotomy model

“…Previously, when porous HAp/Col was implanted into a 5‐mm bone hole created in rabbit tibiae, active bone formation was observed mainly inside the bone marrow cavity and progressed toward the cortical defect, although scarce bone formation was observed inside the bone marrow cavity of the control group without implantation . Studies using a rabbit osteochondral defect model demonstrated an obvious augmentative effect of HAp/Col on bone formation inside the bone marrow cavity, which was also confirmed by quantitative analysis using micro CT imaging . From these observations, given the localization and nature of the bone regeneration, we speculate that bone marrow cells, most likely including stem and progenitor cells, react vigorously and promote active bone formation around and inside the HAp/Col implant.…”

“…From these observations, given the localization and nature of the bone regeneration, we speculate that bone marrow cells, most likely including stem and progenitor cells, react vigorously and promote active bone formation around and inside the HAp/Col implant. In addition to bone conductivity, HAp/Col adsorbs a large amount of BMPs and permits their sustained release . Therefore, HAp/Col is a promising candidate as a BMP carrier for use in a clinical setting.…”

Efficacy of Antibiotic‐Loaded Hydroxyapatite/Collagen Composites Is Dependent on Adsorbability for Treating Staphylococcus aureus Osteomyelitis in Rats

“…In our previous studies, the adsorbability of alendronate and bone morphogenetic protein 2 (BMP‐2) to HAp/Col was demonstrated . We have reported that the adsorbability of BMP‐2 onto HAp/Col enables long‐term release and enhances the bone formation in rat bone defect model …”

“…12 In our previous studies, the adsorbability of alendronate and bone morphogenetic protein 2 (BMP-2) to HAp/Col was demonstrated. [13][14][15] We have reported that the adsorbability of BMP-2 onto HAp/Col enables long-term release and enhances the bone formation in rat bone defect model. 15 The objective of the present study is to investigate the feasibility of local antibiotic administration in the acute phase of a traumatic osteomyelitis model in rats using HAp/Col as a drug delivery system.…”

Current perspectives on biological approaches for osteoarthritis

“…Bone morphogenetic protein (BMP), a macromolecule that belongs to the TGF-␤ family, has a vital role in the development of bone and cartilage, as well 31 BMP subgroups have several diverse functions in chondrogenesis and osteogenesis, but are mainly involved in cell recruitment and stimulating MSC differentiation. 25,32 BMPs have been largely studied in the tendonbone junction, 33 subchondral and osteochondral defects, 34 nonunions, [35][36][37] fracture repair, 38,39 and spinal fusions. 38,40,41 Viral and nonviral gene products, as well as scaffold composites, have been used to deliver individual BMPs or a combination of BMPs, such as BMP-2, 42-44 -6, 45 -7, 46 and -9, 47 for osteochondral defects in preclinical models.…”