MATERIALS AND METHODS: A melatonin-loaded alginate-chitosan/beta-tricalcium phosphate composite hydrogel was successfully prepared and characterized. Thirty-six critical-sized bilateral class II furcation defects were created in six Mongrel dogs, and were randomly divided and allocated to three cohorts; sham, unloaded composite, and melatonin-loaded. Periodontal regenerative capacity was evaluated via histologic and histomorphometric analysis.

RESULTS: Melatonin-treated group showed accelerated bone formation and advanced maturity, with a significant twofold increase in newly formed inter-radicular bone compared with the unloaded composite. The short-term regenerative efficacy was evident 4 weeks postoperatively as a significant increase in cementum length concurrent with reduction of entrapped epithelium. After 8 weeks, the scaffold produced a quality of newly synthesized bone similar to normal compact bone, with potent periodontal ligament attachment.

METHODS: Review of the literature was conducted using keywords (and MeSH) like Bioreactor, Regenerative Dentistry, Fourth Factor, Stem Cells, etc., from the journals published in English. All the searched abstracts, published in indexed journals were read and reviewed to further refine the list of included articles. Based on the relevance of abstracts pertaining to the manuscript, full-text articles were assessed.

RESULTS: Bioreactors provide a prerequisite platform to create, test, and validate the biomaterials and techniques proposed for dental tissue regeneration. Flow perfusion, rotational, spinner-flask, strain and customize-combined bioreactors have been applied for the regeneration of bone, periodontal ligament, gingiva, cementum, oral mucosa, temporomandibular joint and vascular tissues. Customized bioreactors can support cellular/biofilm growth as well as apply cyclic loading. Center of disease control & dip-flow biofilm-reactors and micro-bioreactor have been used to evaluate the biological properties of dental biomaterials, their performance assessment and interaction with biofilms. Few case reports have also applied the concept of in vivo bioreactor for the repair of musculoskeletal defects and used customdesigned bioreactor (Aastrom) to repair the defects of cleft-palate.