The craniofacial region contains skin, bones, cartilage, the temporomandibular joint (TMJ), teeth, periodontal tissues, mucosa, salivary glands, muscles, nerves, and blood vessels. Applying tissue engineering therapeutically helps replace lost tissues after trauma or cancer. Despite recent advances, it remains essential to standardize and validate the most appropriate animal models to effectively translate preclinical data to clinical situations. Therefore, this review focused on applying various animal models in craniofacial tissue engineering and regeneration. This research was based on PubMed, Scopus, and Google Scholar data available until January 2023. This study included only English-language publications describing animal models' application in craniofacial tissue engineering (in vivo and review studies). Study selection was based on evaluating titles, abstracts, and full texts. The total number of initial studies was 6454. Following the screening process, 295 articles remained on the final list. Numerous in vivo studies have shown that small and large animal models can benefit clinical conditions by assessing the efficacy and safety of new therapeutic interventions, devices, and biomaterials in animals with similar diseases/defects to humans. Different species' anatomical, physiologic, and biological features must be considered in developing innovative, reproducible, and discriminative experimental models to select an appropriate animal model for a specific tissue defect. As a result, understanding the parallels between human and veterinary medicine can benefit both fields. 

Exploring the Use of Animal Models in Craniofacial Regenerative Medicine: A Narrative Review

Protected by the surrounding mineralized barriers of enamel, dentin, and cementum, dental pulp is a functionally versatile tissue that fulfills multiple roles [...]

Engineering the Future of Dental Health: Exploring Molecular Advancements in Dental Pulp Regeneration

Regenerative endodontics: repair or true regeneration? A narrative review

Dental pulp stem cells (DPSCs) originate from the neural crest and the present mesenchymal phenotype showed self-renewal capabilities and can differentiate into at least three lineages. DPSCs are easily isolated with minimal harm, no notable ethical constraints, and without general anesthesia to the donor individuals. Furthermore, cryopreservation of DPSCs provides this opportunity for autologous transplantation in future studies without fundamental changes in stemness, viability, proliferation, and differentiating features. Current approaches for pulp tissue regeneration include pulp revascularization, cell-homing-based regenerative endodontic treatment (RET), cell-transplantation-based regenerative endodontic treatment, and allogeneic transplantation. In recent years, a novel technology, organoid, provides a mimic physiological condition and tissue construct that can be applied for tissue engineering, genetic manipulation, disease modeling, single-cell high throughput analysis, living biobank, cryopreserving and maintaining cells, and therapeutic approaches based on personalized medicine. The organoids can be a reliable preclinical prediction model for evaluating cell behavior, monitoring drug response or resistance, and comparing healthy and pathological conditions for therapeutic and prognostic approaches. In the current review, we focused on the promising application of 3D organoid technology based on DPSCs in oral and maxillofacial tissue regeneration. We discussed encountering challenges and limitations, and found promising solutions to overcome obstacles. 

Regenerative application of oral and maxillofacial 3D organoids based on dental pulp stem cell

Regenerative endodontics therapy (RET) is a pioneering approach in dentistry that aims to restore damaged dental pulp and promote tissue regeneration in non-vital teeth. It belongs to the broader field of regenerative medicine, where stem cells, scaffolds, and bioactive molecules are central components. The goal of RET is to achieve true tissue regeneration, fully restoring both the structure and function of damaged tissues, in contrast to repair, which only restores basic functionality through scar formation or tissue remodeling. Histological studies conducted in various research models, ranging from animal studies to human case studies, have provided valuable insights into the nature of tissue regeneration in RET. However, the quality of regenerated tissue can vary significantly among studies. Some research reports have described the presence of fibrous or fibrovascular tissue with limited functionality, resembling repair rather than true regeneration. This variation can be attributed to the impact of disinfection protocols on stem cell viability and differentiation potential. In conclusion, RET has the potential for both repair and true regeneration processes, with outcomes influenced by factors such as disinfection methods and the source of stem cells. Despite the remaining challenges, promising results suggest that RET could revolutionize dental pulp regeneration, especially when approaches that utilize the body\'s stem cells are optimized for clinical use. Further research and protocol refinement is essential to fully unlock the regenerative potential of this exciting field.

Efforts to heal damaged pulp tissue through tissue engineering have produced positive results in pilot trials. However, the differentiation between real regeneration and mere repair is not possible through clinical measures. Therefore, preclinical study models are still of great importance, both to gain insights into treatment outcomes on tissue and cell levels and to develop further concepts for dental pulp regeneration. This review aims at compiling information about different in vitro and in vivo ectopic, semiorthotopic, and orthotopic models. In this context, the differences between monolayer and three-dimensional cell cultures are discussed, a semiorthotopic transplantation model is introduced as an in vivo model for dental pulp regeneration, and finally, different animal models used for in vivo orthotopic investigations are presented.

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A Compilation of Study Models for Dental Pulp Regeneration

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A Compilation of Study Models for Dental Pulp Regeneration