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Effect of local administration of microRNA-31/210 on bone regeneration surrounding hydroxyapatite/tricalcium
Shinichi Ueki1, Takeshi Shoji1, Hideki Saka2
1Department of Orthopaedical Surgery, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami, Hiroshima 734-8551, Japan.
Background:
With the aging population, the prevalence of total joint arthroplasty in older adults with compromised bone conditions, such as osteoporosis, is increasing, raising concerns on the initial fixation of implants and aseptic loosening. Recent studies have highlighted the potential of microRNAs (miRNAs) to enhance osteogenesis and angiogenesis, potentially improving implant osseointegration. This study aimed to identify miRNAs with the highest osteogenic and angiogenic potential in vitro, and evaluate its effects on implant osseointegration and surrounding bone regeneration in an ovariectomized (OVX) rat model.
Methods:
In vitro studies were conducted to identify miRNAs exhibiting the greatest osteogenic and angiogenic potential among candidate miRNAs (miR-31, -34a, -146, -210, -218, and -31 + 210). Subsequently, the most effective miRNA was selected and locally administered to the bone matrix, where hydroxyapatite/tricalcium phosphate (HA/TCP)-coated titanium implants were placed in the femurs of OVX rats for in vivo studies. At 2, 4, and 8 weeks post-implantation, implant osseointegration, osteogenesis, angiogenesis of the matrix bone, and the initial fixation of the implant were evaluated using histological, genetic, radiological, and biomechanical assessments.
Results:
miR-31 and miR-210 were strongly associated with osteogenesis, whereas miR-31 was strongly associated with angiogenesis. Moreover, the simultaneous administration of miR-31 and miR-210 resulted in the highest osteogenic potential among the miRNAs tested. In the OVX rat model, local administration of miR-31 + 210 significantly enhanced implant osseointegration, osteogenesis, angiogenesis within the bone matrix, and initial fixation of the implant compared to controls.
Conclusion:
Local administration of miR-31 + 210 around HA/TCP-coated implants effectively improved implant osseointegration, the bone matrix environment, and initial fixation of implants in osteoporotic bone, likely by promoting osteogenesis and angiogenesis. This strategy holds promise as a novel regeneration therapy for enhancing implant fixation in patients with poor bone quantity.
