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Volume 16
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10.3390/jfb16120438
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Review

Rat Calvarial Guided Bone Regeneration Model: Preclinical Insights into Biomaterials, Barrier Design, and Systemic Modulators

by
Akira Hasuike
1,2,*,
Taito Watanabe
1,
Shin Wakuda
1,
Tomoe Suzuki
1,3,
Shuto Kikuchi
1,3,
Seiko Min
4,
Yoshinori Arai
5 and
Shuichi Sato
1,2
1
Department of Periodontology, Nihon University School of Dentistry, Tokyo 101-8310, Japan
2
Dental Research Center, Nihon University School of Dentistry, Tokyo 101-8310, Japan
3
Division of Applied Oral Sciences, Nihon University Graduate School of Dentistry, Tokyo 101-8310, Japan
4
Department of Periodontics and Dental Hygiene, University of Texas Health Science Center at Houston, Houston, TX 77054, USA
5
Department of Oral and Maxillofacial Radiology, Nihon University Graduate School of Dentistry, Tokyo 101-8310, Japan
*
Author to whom correspondence should be addressed.
J. Funct. Biomater. 2025, 16(12), 438; https://doi.org/10.3390/jfb16120438
Submission received: 10 October 2025 / Revised: 26 October 2025 / Accepted: 24 November 2025 / Published: 25 November 2025
(This article belongs to the Section Bone Biomaterials)
Versions Notes

Abstract

Guided bone regeneration (GBR) plays a key role in alveolar ridge augmentation and implant therapy, but the biological mechanisms governing its outcomes are not fully understood. Preclinical animal models provide critical insights that cannot be obtained in early human studies. Over the past 15 years, our group has developed and optimized a standardized rat calvarial GBR model using plastic caps, enabling reproducible and quantitative evaluation of bone regeneration through micro-computed tomography and histomorphometry. The present narrative review synthesizes the findings from our body of work. Our studies demonstrated that advanced substitutes such as hydroxyapatite/collagen composites and carbonate apatite provide favorable outcomes, indicating that local and systemic application of growth factors or parathyroid hormone can markedly enhance augmentation, and that barrier permeability critically modulates angiogenesis and osteogenesis. Moreover, systemic conditions such as nicotine exposure and estrogen deficiency profoundly compromise regenerative outcomes but can be partly mitigated by pharmacological interventions. Finally, regenerated bone within GBR spaces is biologically competent, although it remains less mature than native cortical bone. Together, these insights highlight the translational value of our GBR model and indicate the integration of spatial omics for the elucidation of the cellular mechanisms that will guide future regenerative strategies.
Keywords: guided bone regeneration; rat calvarial model; bone substitutes; barrier membranes; growth factors; systemic conditions; carbonate apatite; spatial omics guided bone regeneration; rat calvarial model; bone substitutes; barrier membranes; growth factors; systemic conditions; carbonate apatite; spatial omics

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MDPI and ACS Style

Hasuike, A.; Watanabe, T.; Wakuda, S.; Suzuki, T.; Kikuchi, S.; Min, S.; Arai, Y.; Sato, S. Rat Calvarial Guided Bone Regeneration Model: Preclinical Insights into Biomaterials, Barrier Design, and Systemic Modulators. J. Funct. Biomater. 2025, 16, 438. https://doi.org/10.3390/jfb16120438

AMA Style

Hasuike A, Watanabe T, Wakuda S, Suzuki T, Kikuchi S, Min S, Arai Y, Sato S. Rat Calvarial Guided Bone Regeneration Model: Preclinical Insights into Biomaterials, Barrier Design, and Systemic Modulators. Journal of Functional Biomaterials. 2025; 16(12):438. https://doi.org/10.3390/jfb16120438

Chicago/Turabian Style

Hasuike, Akira, Taito Watanabe, Shin Wakuda, Tomoe Suzuki, Shuto Kikuchi, Seiko Min, Yoshinori Arai, and Shuichi Sato. 2025. "Rat Calvarial Guided Bone Regeneration Model: Preclinical Insights into Biomaterials, Barrier Design, and Systemic Modulators" Journal of Functional Biomaterials 16, no. 12: 438. https://doi.org/10.3390/jfb16120438

APA Style

Hasuike, A., Watanabe, T., Wakuda, S., Suzuki, T., Kikuchi, S., Min, S., Arai, Y., & Sato, S. (2025). Rat Calvarial Guided Bone Regeneration Model: Preclinical Insights into Biomaterials, Barrier Design, and Systemic Modulators. Journal of Functional Biomaterials, 16(12), 438. https://doi.org/10.3390/jfb16120438

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