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

Abstract

In fracture treatment, biological bone union generally depends on the bone's natural fracture healing capacity, even in surgically treated cases. Hydroxyapatite/collagen composite (HAp/Col) has high osteoconductivity and stimulates osteogenic progenitors. Furthermore, it has the potent capacity to adsorb bone morphogenetic proteins (BMPs). In this study, we prepared an injectable HAp/Col paste and evaluated its augmentation of bone union. Furthermore, the effect of HAp/Col paste combined with BMP-2 was also evaluated. We used a rat femur osteotomy model with a defect size of 1 mm. Male Wistar rats were assigned to one of the following four groups; a control group without any implant, a HAp/Col implant group, a group that received an absorbable collagen sponge (ACS) implant impregnated with BMP-2 (1 μg), and a group that received a HAp/Col implant impregnated with BMP-2 implant. Micro-CT analysis, three-point bending tests, and histological evaluation were performed. Bone union was achieved in two of eight cases in the HAp/Col group, five of eight cases in the ACS + BMP-2 group, and all cases in the HAp/Col + BMP-2 group at 8 weeks post-surgery. The control group did not achieve bone union. In addition, in the HAp/Col + BMP-2 group, the biomechanical strength of the fused femurs was comparable to that of the contralateral intact femur; the ratio of the mechanical load at the breaking point of the osteotomy side relative to that of the contralateral side was 1.00 ± 0.151 (SD). These results indicate that HAp/Col paste with or without BMP-2 augments bone union. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:129-137, 2018.

<p>Enhancement of bone consolidation using high-frequency pulsed electromagnetic short-waves and titanium implants coated with biomimetic composite embedded into PLA matrix: in vivo evaluation</p>

“…Compared to the paste of HAP and COL that can physically disperse and its effect may decrease much faster than desired,68 the use of titanium coated with calcined HAP-COL provides both mechanical stability and rigidity of the fixing method, maintaining long-term osteoconductive properties 69. Furthermore, substituted HAP in physiological conditions continuously releases its ions,70 with specific effects in the bone biochemistry and homeostasis 71.…”

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.…”

“…[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. Given that Staphylococcus aureus has been demonstrated clinically to be the most common causative pathogen for osteomyelitis, 16 we will likewise examine S. aureus in our rat model of osteomyelitis.…”

Bone regeneration is enhanced by the combined use of acid‐electrolyzed functional water with hydroxyapatite/collagen composite

“…Various materials have been developed for bone defect repair (Itoh, Kikuchi, Takakuda, et al, ). We selected the HAP/Col composite because of its usefulness in various experimental models (Jung et al, ; Schneiders et al, ; Tsuchiya et al, ; Wei et al, ), and as a carrier for various recombinant proteins (Itoh et al, ; Itoh, Kikuchi, Koyama, et al, ; Itoh, Kikuchi, Takakuda, et al, ; Maehara et al, ; Sotome et al, ). Moreover, HAP/Col has been used in the clinical field due to its structural similarities to natural bone (Sotome et al, ).…”