Translating Dental, Oral, and Craniofacial Regenerative Medicine Innovations to the Clinic through Interdisciplinary Commercial Translation Architecture

Abstract

Few university-based regenerative medicine innovations in the dental, oral, and craniofacial (DOC) space have been commercialized and affected clinical practice in the United States. An analysis of the commercial translation literature and National Institute for Dental and Craniofacial Research’s (NIDCR’s) portfolio identified barriers to commercial translation of university-based DOC innovations. To overcome these barriers, the NIDCR established the Dental Oral Craniofacial Tissue Regeneration Consortium. We provide generalized strategies to inform readers how to bridge the “valley of death” and more effectively translate DOC technologies from the research laboratory or early stage company environment to clinical trials and bring needed innovations to the clinic. Three valleys of death are covered: 1) from basic science to translational development, 2) from translational technology validation to new company formation (or licensing to an existing company), and 3) from new company formation to scaling toward commercialization. An adapted phase-gate model is presented to inform DOC regenerative medicine teams how to involve regulatory, manufacturability, intellectual property, competitive assessments, business models, and commercially oriented funding mechanisms earlier in the translational development process. An Industrial Partners Program describes how to conduct market assessments, industry maps, business development processes, and industry relationship management methods to sustain commercial translation through the later-stage valley of death. Paramount to successfully implementing these methods is the coordination and collaboration of interdisciplinary teams around specific commercial translation goals and objectives. We also provide several case studies for translational projects with an emphasis on how they addressed DOC biomaterials for tissue regeneration within a rigorous commercial translation development environment. These generalized strategies and methods support innovations within a university-based and early stage company-based translational development process, traversing the many funding gaps in dental, oral, and craniofacial regenerative medicine innovations. Although the focus is on shepherding technologies through the US Food and Drug Administration, the approaches are applicable worldwide.

Bench-to-bedside: Feasibility of nano-engineered and drug-delivery biomaterials for bone-anchored implants and periodontal applications

“…The final step in translating an innovative drug delivery product for the market application is related to receiving approval from the controlling agencies and, in an appropriate order, the release into the market. However, this step has been reported as “the valley of death” due to the complexity of completing the product translation [ 16 , 107 ]. Three main points have been established regarding the requirements for successful translation and to overcome this gap: 1) basic research focused on translational products; 2) technology validation for subsequent company development; and 3) company formation with a focus on large-scale production [ 16 ] ( Fig.…”

“…However, this step has been reported as “the valley of death” due to the complexity of completing the product translation [ 16 , 107 ]. Three main points have been established regarding the requirements for successful translation and to overcome this gap: 1) basic research focused on translational products; 2) technology validation for subsequent company development; and 3) company formation with a focus on large-scale production [ 16 ] ( Fig. 4 ).…”

“…Lastly, the biggest challenges for the translation of BDDSs to the market are the clinical trials and their commercial approval by the responsible entities. Different reports have shown the difficulty of receiving commercial approval and/or demonstrate a major delay in the approval process [ 15 , 16 ] – consequences that often discourage funding bodies or even researchers themselves from continuing their development. Thus, the aim of this critical literature review is to clarify and detail the main steps and the main challenges involved in the development, analysis, and regulatory approval of BDDSs for clinical translation, as well as, the promising shift that biomaterials with drug-delivery systems and/or nano-engineered features may promote in the future clinical sector.…”

Dental Medicine and Engineering Unite to Transform Oral Health Innovations

“…The development of cross-trained talent at predoctoral and doctoral levels will provide a pipeline for postdoctoral and faculty recruitment. Importantly, established programs in tissue regeneration and clinical translation (e.g., Michigan-Pittsburgh-Wyss-Regenerative Medicine [Taylor et al 2021] (2021) to promote partnerships in oral health technologies can facilitate entrepreneurship and accelerate innovation. Similar initiatives are developing worldwide.…”

Interface between Materials and Oral Biology

“…This special issue of the Journal of Dental Research contains 4 state-of-the-art critical reviews tackling regenerative engineering (Hosseini et al, 2021), oral biomineralization (Moradian-Oldak and George, 2021), advanced testing modalities for dental restorations (Zhang et al, 2021), and the important factors involved in commercializing new innovations in regenerative materials (Taylor et al, 2021). The complex interactions occurring between biomaterials and fluids, as well as living cells and tissues in the oral environment, are highlighted in a series of 17 original research reports.…”