A composite critical-size rabbit mandibular defect for evaluation of craniofacial tissue regeneration

Developers

Sarita R. Shah, Simon Young, Julia L. Goldman, Mark E. Wong, Antonios G. Mikos, etc.

Description of the technology

The technology reproduces a load-bearing critical-size composite tissue defect comprising loss of soft tissue, bone and tooth in the mandible of a rabbit.

The biomaterials targeted toward the regeneration of large bone defects in the mandible require a preclinical model that accurately recapitulates the regenerative challenges present in humans. Computational modeling and in vitro assays do not fully replicate the in vivo environment. Consequently, in vivo models can have specific applications such as those of the mandibular angle defect, which is used to investigate bone regeneration in a non-load-bearing area, or the inferior border mandibular defect, which is a model for composite bone and nerve regeneration, with both models avoiding involvement of soft tissue or teeth.
Earlier the model of defect used in this technology has been applied to investigate bone regeneration, vascularization and infection prevention in response to new biomaterial formulations for craniofacial tissue engineering applications. This surgical approach can be adapted to investigate processes such as that of regeneration in the context of osteoporosis or irradiation. The procedure can be performed by researchers with basic surgical skills such as dissection and suturing. The procedure takes 1.5–2 h, with ~2 h of immediate postoperative care, and animals should be monitored daily for the remainder of the study. For bone tissue engineering applications, tissue collection typically occurs 12 weeks after surgery. The protocol of the technology includes all necessary steps to ensure reproducibility; tips to minimize complications during and after surgery; and analytical techniques for assessing soft tissue, bone and vessel regeneration by gross evaluation, microcomputed tomography (microCT) and histology.

Practical application

The technology is promising for experimental application in the field of regenerative medicine.
The technology allows the investigator to use a single surgical approach to evaluate specific anatomic or therapy-based variations. It is applicable to a wide variety of tissue engineering constructs, such as new biomaterials and drug-releasing implants.

Besides, it could also be used to address other areas of importance in craniofacial tissue engineering and dental applications, such as tooth regeneration, simultaneous alveolar bone and tooth regeneration, barrier membrane regeneration and tissue regeneration combined with dental implants.

This model can also be expanded to include rabbits that undergo treatment to model compromised populations. For example, rabbits can be ovariectomized before surgery in order to evaluate tissue regeneration in an osteoporotic population. Thus, this model is applicable for investigations in the field of ageing study.

Laboratories

• Department of Bioengineering, Rice University, Houston (USA)
• Department of Oral and Maxillofacial Surgery, University of Texas Health Science Center at Houston, Houston (USA)
• Center for Laboratory Animal Medicine and Care, University of Texas Health Science Center at Houston, Houston (USA)
• Department of Biomaterials, Radboud University Medical Center, Nijmegen (the Netherlands)

Links

Publications

• Shah, S.R. et al. «A composite critical-size rabbit mandibular defect for evaluation of craniofacial tissue regeneration." 11 Nature Protocols (2016): 1989–2009.
• Smith, B.T. et al. «Bone tissue engineering challenges in oral & maxillofacial surgery." 881 Adv. Exp. Med. Biol. (2015): 57–78.
• Tatara, A.M. et al. «Infected animal models for tissue engineering." 84 Methods (2015): 17–24.