Bone regeneration using moldable calcium phosphate with and without recombinant human BMP-2 in a rabbit critical-sized metaphyseal core defect model
Abstract Background Moldable calcium phosphate (MCaP) biomaterials have been studied as osteoconductive scaffolds for bone regeneration. However, their potential as carriers for recombinant human bone morphogenetic protein-2 (rhBMP-2) and the biological impact of varying rhBMP-2 doses remain to be f...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
|
| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-025-05966-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850224372578516992 |
|---|---|
| author | Hyun Seung Ryu Hyun Jung Park Mi Young Ryu Young-Hoon Kim Sang-Il Kim Hyung-Youl Park |
| author_facet | Hyun Seung Ryu Hyun Jung Park Mi Young Ryu Young-Hoon Kim Sang-Il Kim Hyung-Youl Park |
| author_sort | Hyun Seung Ryu |
| collection | DOAJ |
| description | Abstract Background Moldable calcium phosphate (MCaP) biomaterials have been studied as osteoconductive scaffolds for bone regeneration. However, their potential as carriers for recombinant human bone morphogenetic protein-2 (rhBMP-2) and the biological impact of varying rhBMP-2 doses remain to be fully validated. This study aimed to evaluate the efficacy and safety of MCaP alone and in combination with rhBMP-2 in a rabbit metaphyseal bone defect model. Methods Bilateral critical-sized metaphyseal core defects were created in the distal femurs of 73 skeletally mature female New Zealand White rabbits. Animals were assigned to six groups: sham, autograft, MCaP alone, or MCaP combined with low (0.04 mg/cc), mid (0.16 mg/cc), or high (0.6 mg/cc) doses of rhBMP-2. Bone formation and healing were assessed at 3 days and 3, 6, and 12 weeks using radiography, microcomputed tomography (μCT), histomorphometry, and histopathology. Local tissue reactions were evaluated according to ISO 10993–6 standards, and systemic toxicity was assessed through distant organ examinations. Results Radiographic and μCT analyses showed progressive bone formation in all treatment groups. Compared with autografts, both the MCaP and rhBMP-2-treated groups exhibited significantly higher bone in the region of interest at 6 and 12 weeks (p < 0.05), with no significant differences between the MCaP-only and rhBMP-2 groups. Histological evaluation revealed earlier and more active bone regeneration in rhBMP-2–treated groups, particularly at higher doses. Minimal inflammatory responses were observed across all groups, and no systemic toxicity was detected, supporting the biocompatibility and safety of MCaP-based constructs. Conclusions The MCaP carrier demonstrated strong osteoconductive potential and was sufficient to support bone healing compared to autograft in a metaphyseal defect model. The addition of rhBMP-2 promoted earlier bone formation. However, long-term studies in more challenging bone healing environments are warranted to further assess the clinical utility of rhBMP-2 in bone regeneration. |
| format | Article |
| id | doaj-art-d8e02537d1bb4508a961d56390bcd46b |
| institution | OA Journals |
| issn | 1749-799X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj-art-d8e02537d1bb4508a961d56390bcd46b2025-08-20T02:05:38ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2025-06-0120111410.1186/s13018-025-05966-yBone regeneration using moldable calcium phosphate with and without recombinant human BMP-2 in a rabbit critical-sized metaphyseal core defect modelHyun Seung Ryu0Hyun Jung Park1Mi Young Ryu2Young-Hoon Kim3Sang-Il Kim4Hyung-Youl Park5Department of Research Center, CGBio Co., Ltd.Department of Research Center, CGBio Co., Ltd.Department of Research Center, CGBio Co., Ltd.Department of Orthopedic Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaDepartment of Orthopedic Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaDepartment of Orthopedic Surgery, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of KoreaAbstract Background Moldable calcium phosphate (MCaP) biomaterials have been studied as osteoconductive scaffolds for bone regeneration. However, their potential as carriers for recombinant human bone morphogenetic protein-2 (rhBMP-2) and the biological impact of varying rhBMP-2 doses remain to be fully validated. This study aimed to evaluate the efficacy and safety of MCaP alone and in combination with rhBMP-2 in a rabbit metaphyseal bone defect model. Methods Bilateral critical-sized metaphyseal core defects were created in the distal femurs of 73 skeletally mature female New Zealand White rabbits. Animals were assigned to six groups: sham, autograft, MCaP alone, or MCaP combined with low (0.04 mg/cc), mid (0.16 mg/cc), or high (0.6 mg/cc) doses of rhBMP-2. Bone formation and healing were assessed at 3 days and 3, 6, and 12 weeks using radiography, microcomputed tomography (μCT), histomorphometry, and histopathology. Local tissue reactions were evaluated according to ISO 10993–6 standards, and systemic toxicity was assessed through distant organ examinations. Results Radiographic and μCT analyses showed progressive bone formation in all treatment groups. Compared with autografts, both the MCaP and rhBMP-2-treated groups exhibited significantly higher bone in the region of interest at 6 and 12 weeks (p < 0.05), with no significant differences between the MCaP-only and rhBMP-2 groups. Histological evaluation revealed earlier and more active bone regeneration in rhBMP-2–treated groups, particularly at higher doses. Minimal inflammatory responses were observed across all groups, and no systemic toxicity was detected, supporting the biocompatibility and safety of MCaP-based constructs. Conclusions The MCaP carrier demonstrated strong osteoconductive potential and was sufficient to support bone healing compared to autograft in a metaphyseal defect model. The addition of rhBMP-2 promoted earlier bone formation. However, long-term studies in more challenging bone healing environments are warranted to further assess the clinical utility of rhBMP-2 in bone regeneration.https://doi.org/10.1186/s13018-025-05966-yBone regenerationCritical-sized defectMetaphyseal boneMoldable calcium phosphateRecombinant human bone morphogenetic protein-2 (rhBMP-2)Bone graft substitute |
| spellingShingle | Hyun Seung Ryu Hyun Jung Park Mi Young Ryu Young-Hoon Kim Sang-Il Kim Hyung-Youl Park Bone regeneration using moldable calcium phosphate with and without recombinant human BMP-2 in a rabbit critical-sized metaphyseal core defect model Journal of Orthopaedic Surgery and Research Bone regeneration Critical-sized defect Metaphyseal bone Moldable calcium phosphate Recombinant human bone morphogenetic protein-2 (rhBMP-2) Bone graft substitute |
| title | Bone regeneration using moldable calcium phosphate with and without recombinant human BMP-2 in a rabbit critical-sized metaphyseal core defect model |
| title_full | Bone regeneration using moldable calcium phosphate with and without recombinant human BMP-2 in a rabbit critical-sized metaphyseal core defect model |
| title_fullStr | Bone regeneration using moldable calcium phosphate with and without recombinant human BMP-2 in a rabbit critical-sized metaphyseal core defect model |
| title_full_unstemmed | Bone regeneration using moldable calcium phosphate with and without recombinant human BMP-2 in a rabbit critical-sized metaphyseal core defect model |
| title_short | Bone regeneration using moldable calcium phosphate with and without recombinant human BMP-2 in a rabbit critical-sized metaphyseal core defect model |
| title_sort | bone regeneration using moldable calcium phosphate with and without recombinant human bmp 2 in a rabbit critical sized metaphyseal core defect model |
| topic | Bone regeneration Critical-sized defect Metaphyseal bone Moldable calcium phosphate Recombinant human bone morphogenetic protein-2 (rhBMP-2) Bone graft substitute |
| url | https://doi.org/10.1186/s13018-025-05966-y |
| work_keys_str_mv | AT hyunseungryu boneregenerationusingmoldablecalciumphosphatewithandwithoutrecombinanthumanbmp2inarabbitcriticalsizedmetaphysealcoredefectmodel AT hyunjungpark boneregenerationusingmoldablecalciumphosphatewithandwithoutrecombinanthumanbmp2inarabbitcriticalsizedmetaphysealcoredefectmodel AT miyoungryu boneregenerationusingmoldablecalciumphosphatewithandwithoutrecombinanthumanbmp2inarabbitcriticalsizedmetaphysealcoredefectmodel AT younghoonkim boneregenerationusingmoldablecalciumphosphatewithandwithoutrecombinanthumanbmp2inarabbitcriticalsizedmetaphysealcoredefectmodel AT sangilkim boneregenerationusingmoldablecalciumphosphatewithandwithoutrecombinanthumanbmp2inarabbitcriticalsizedmetaphysealcoredefectmodel AT hyungyoulpark boneregenerationusingmoldablecalciumphosphatewithandwithoutrecombinanthumanbmp2inarabbitcriticalsizedmetaphysealcoredefectmodel |