New insights into and novel applications of release technology for periodontal reconstructive therapies.

Periodontitis, an almost ubiquitous disorder in the adult population, induces the breakdown of tooth-supporting apparatus which, unfortunately, has an extremely limited capacity for self-repair and regeneration. The recent discovery of progenitor/stem cells residing in the periodontium, however, raises the possibility of restoring damaged periodontal tissues by recruiting their latent regenerative potential. Within the reparative process, stem cell fates may be influenced by a number of signaling molecules, such as growth factors (GFs), that require robust control for safe and effective regeneration of functional tissues. Numerous GFs with the ability to promote the regeneration of periodontal tissues have been identified thus far, but their clinical use is often hindered by delivery problems. Regulation of cell activity within a complex in vivo milieu requires the incorporation of multifaceted release technologies that offer physiological levels of GFs, mimicking the natural wound healing cascade by using tools of tissue engineering and protein/gene delivery. This should not be limited to the provision of a single GF but should instead release multiple essential GFs at an optimized ratio in a specific spatiotemporal mode. This article summarizes current limitations and new opportunities related to release technology in periodontal regenerative medicine, highlighting the importance as well as challenges with respect to delivering multiple GFs in an orderly temporal and spatial sequence to mimic their natural expression patterns. Recent progress highlights the importance of releasing endogenous GFs and developing commercially available products that may facilitate clinical translation.