ORIGINAL RESEARCH article
Front. Physiol.
Sec. Craniofacial Biology and Dental Research
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1662424
This article is part of the Research TopicRecent Advances in Dental, Oral, and Craniofacial Bone Biology and RegenerationView all articles
Comprehensive Evaluation of Critical-Size Calvarial Defect in Athymic Rat Model
Provisionally accepted
Todd M Parco1Jon D Wagner1Pratish Parbhoo1Caroline Soviak1David Hu1JT Araiza1Colin O'Beirne1Praveen Parachuru1Matthew E Lewis1Carlos Acosta1
Rajendra Prasad Settem2
Toshihisa Kawai3
Umadevi Kandalam1*- 1Woody L. Hunt School of Dental Medicine, Texas Tech University Health Sciences Center, El Paso, United States
- 2University at Buffalo School of Dental Medicine, Buffalo, United States
- 3Nova Southeastern University College of Dental Medicine, Fort Lauderdale, United States
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The critical size defect (CSD), which defines the threshold beyond which spontaneous healing fails, serves as a foundational tool in bone regeneration research. This study investigates calvarial CSDs in an athymic rat model to refine the definition, emphasize its significance, and address inconsistencies in experimental design across existing information. A 4.5 mm diameter calvarial defect was surgically created in athymic rats. Bone regeneration was assessed using micro-computed tomography (micro-CT) at 1, 4, and 8 weeks, compared to the baseline (day 0) post-surgery. Histological assessment was also performed using a standard hematoxylin and eosin (H&E) staining protocol at 8 weeks post-surgery. Quantitative data from micro-CT analysis revealed no increase in bone volume or percentage volume from day 0 to week 1. We observed bone regeneration initiated at week 4 and progressed through week 8, with healing percentages ranging from 0.1% to a maximum of 7%. Histological examination of tissue at week 8 revealed the presence of loose collagen fibers and interspersed fibroblasts, with no mineralization as observed in a mature bone. These findings confirm that the 4.5 mm defect in calvarial bone qualifies as a critical-size defect in the athymic rat model. The study enhances our understanding of bone healing dynamics in CSDs and provides a validated platform for evaluating novel regenerative therapies
Keywords: Critical size defect, calvarial defect, rat, Bone Regeneration, Musculoskeletal disorders
Received: 09 Jul 2025; Accepted: 27 Aug 2025.
Copyright: © 2025 Parco, Wagner, Parbhoo, Soviak, Hu, Araiza, O'Beirne, Parachuru, Lewis, Acosta, Settem, Kawai and Kandalam. 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: Umadevi Kandalam, Woody L. Hunt School of Dental Medicine, Texas Tech University Health Sciences Center, El Paso, United States
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