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Destruction of the alveolar bone in the jaws can occur due to periodontitis, trauma or following tumor resection. Common reconstructive therapy can include the use of bone grafts with limited predictability and efficacy. Romosozumab, approved by the FDA in 2019, is a humanized sclerostin-neutralizing antibody (Scl-Ab) indicated in postmenopausal women with osteoporosis at high risk for fracture. Preclinical models show that Scl-Ab administration preserves bone volume during periodontal disease, repairs bone defects surrounding dental implants, and reverses alveolar bone loss following extraction socket remodeling. To date, there are no studies evaluating Scl-Ab to repair osseous defects around teeth or to identify the efficacy of locally-delivered Scl-Ab for targeted drug delivery. In this investigation, the use of systemically-delivered versus low dose locally-delivered Scl-Ab via poly(lactic-co-glycolic) acid (PLGA) microspheres (MSs) was compared at experimentally-created alveolar bone defects in rats. Systemic Scl-Ab administration improved bone regeneration and tended to increase cementogenesis measured by histology and microcomputed tomography, while Scl-Ab delivered by MSs did not result in enhancements in bone or cemental repair compared to MSs alone or control. In conclusion, systemic administration of Scl-Ab promotes bone and cemental regeneration while local, low dose delivery did not heal periodontal osseous defects in this study.

At present, various tissue engineering strategies in the regenerative medicine have been developed for multiple tissue regeneration and integrative structure formations in musculoskeletal system. However, the regenerations of dental tissues or tooth-supportive structures are still challenging due to the micro-interfacial compartmentalization of multiple tissues, their integrations for systematic responses, and spatiotemporal organizations of engineered fibrous tissues. In particular, the biomaterial-based approaches are limitedly investigated for spatiotemporal controls of periodontal regenerations and challenging to promote micron-scaled interfacial tissue compartmentalization with their integrations for functioning restorations. This chapter demonstrates biomaterial applications for periodontal tissue engineering and the advanced 3D fabrication technologies for preclinical applications and the limited clinical trial using 3D scaffolding systems.

To fully regenerate the periodontal tissues remains a challenge in our daily practice. Periodontal regeneration is a complex process involving a series of cellular and molecular events. In the last two decades, significant advances have been made in applying proteins and peptides to treat periodontal osseous defects. Several products are currently available and a few others are under development. Stem cell therapy has also been vigorously investigated for regenerating craniofacial tissues including periodontia. In this chapter, we review the current status of protein- and cell-based therapies for periodontal regeneration, with an emphasis on products that have been tested in clinical studies.