ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1622918
EP4 receptor stimulation in combination with core decompression therapy enhanced bone regeneration in a canine model of osteonecrosis of femoral head
Provisionally accepted
- 1Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, Izunokuni, Japan
- 2Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu, Japan
- 3Center for One Medicine Innovative Translational Research (COMIT), Gifu University, Gifu, Japan
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Core decompression (CD) is a minimally invasive procedure widely used to treat early-stage osteonecrosis of the femoral head (ONFH). However, CD alone often yields suboptimal outcomes in promoting bone regeneration in necrotic lesions, highlighting the need for novel therapeutic approaches. In this study, we evaluated the combined effects of CD surgery and local administration of AKDS001, a small-molecule EP4 receptor agonist, in a canine ONFH model. AKDS001 was incorporated into biocompatible, biodegradable polylactic-coglycolic acid microspheres (AKDS001 MSs) for sustained local drug release. The bone-regenerative effects of local administration of AKDS001 MSs combined with CD surgery were evaluated in intact canines or a canine ONFH model, induced by ethanol injection into the femoral head. Safety and local tolerability of the therapy was also investigated in the model. AKDS001 MSs enhanced bone formation in intact dog femurs compared to CD only or MSs without AKDS001. In the ONFH model, CD alone resulted in limited bone repair at 12 weeks postsurgery. In contrast, compared with CD alone, the combination of AKDS001 MSs and CD dose-dependently increased the bone volume, bone mineral density, and tissue mineral density in the CD tunnel. Histological analyses further revealed significant amelioration of the necrotic lesions. Importantly, no systemic or local adverse effects were observed. In conclusion, local administration of AKDS001 MSs combined with CD surgery significantly enhanced bone regeneration in necrotic lesions in a canine ONFH model, demonstrating both efficacy and favorable safety with local tolerability.
Keywords: EP4, prostaglandin, Bone Regeneration, Osteonecrosis, Femoral head, dog, animal model
Received: 05 May 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Hirano, Miyagawa, Nishida and Akiyama. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Masahiro Nishida, Laboratory for Pharmacology, Pharmaceutical Research Center, Asahi Kasei Pharma Corporation, Izunokuni, Japan
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