Animal models for bone tissue engineering and modelling disease

Abstract

Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches.

Photobiomodulation Therapy Associated with Heterologous Fibrin Biopolymer and Bovine Bone Matrix Helps to Reconstruct Long Bones

“…The choice of long bones such as the tibia for bone repair is related to its ease of manipulation and access and its similarity to the clinical application in humans, regarding remodeling, repair in the physiology of muscle strength and tension. When dealing with critical defects, larger animals should be used, such as sheep and pigs [31,33,34,36,42]. In addition, biomaterials are used in orthopedic medical surgeries performed to correct bone defects of dimensions that do not spontaneously repair, as well as in patients with osteoporosis or cancer [42,43].…”

The Impact of Bioceramic Scaffolds on Bone Regeneration in Preclinical In Vivo Studies: A Systematic Review

“…Although studies in dogs, minipigs, sheep, and non-human primates, could provide a better insight into new bone formation and scaffold effectiveness thanks to the closer resemblance to the human bone, only studies employing rat and rabbit models were found to satisfy eligibility criteria, and were, therefore, included in the present systematic review [21,[27][28][29]126]. Even though after the first step of screening, studies in dogs, sheep, and pigs were included, the full-text analysis revealed that most of these studies did not meet the selection criteria due to a reduced sample size (n < 6 animals per group) or the non-critical dimensions of the bone defects [94,100,102,103,106].…”

The Role of Strontium Enriched Hydroxyapatite and Tricalcium Phosphate Biomaterials in Osteoporotic Bone Regeneration

“…In our study, we chose to establish a non-critical bone defect in rabbits femoral neck area, as it is an increasing problem for humans, being the most affected osteoporotic fracture. Other authors have used mandible, tibial or distal femur critical or non-critical bone defects for biomaterial applications [33,34].…”