We seek to recruit interdisciplinary translational project (ITP) teams from universities and industry nationwide that align with our clinical indication priorities in dental, oral, and craniofacial tissue engineering/regenerative medicine. Our first RFP was issued in May 2017 and the first cohort of ITP teams was selected in November 2017. The second cohort of ITP teams was selected in June 2018. We are currently soliciting additional projects through our Summer 2018 RFP, with pre-proposals due July 27, 2018.

We are developing an ITP team pipeline, as shown in the figure at right, through a process of structured innovation, during which we recruit, select, and advance only those technologies that optimally align with priorities of four key stakeholder groups — providers (clinicians and healthcare networks); producers (industry); payors; and patients.

ITP teams funded through our Winter 2017/2018 cycle

Novel drug candidate for therapy of arthritis of the TMJ - Denis Evseenko, MD, PhD (USC)

Replacement salivary tissues for relief of xerostomia - Mary C. Farach-Carson, PhD (University of Texas)

PILP: a novel method to repair dentin caries - Stefan Habelitz, PhD (UCSF)

HB-EGF for radiation-induced oral mucositis - Peter Santa Maria, MD, PhD (Stanford)

 

ITP teams funded through our Summer 2017 cycle

Stem cell-based therapies for bone regeneration around ailing dental implants - Tara Aghaloo, DDS, MD, PhD (UCLA)

An osteoconductive growth factor-free antimicrobial adhesive for treatment of peri-implantitis - Nasim Annabi, PhD (Northeastern University)

Calvarial bone regeneration using mesenchymal stem cells in swine - Yang Chai, DDS, PhD (USC)

Prevention of scar formation in the skin using topical focal adhesion kinase inhibitors - Geoffrey Gurtner, MD (Stanford University)

Promoting salivary gland regeneration using therapeutic delivery of carbachol - Sarah Knox, PhD (UCSF)

Mitigating radiation induced hyposalivation by activation of ALDH3A1 - Quynh-Thu Le, MD, FACR, FASTRO (Stanford University)

We have found that activation of ALDH3a1 enzyme, which is enriched in salivary stem cells, increased stem cell yield, and preserved saliva functions after irradiation in mice. We have discovered a natural product compound, Alda-341, that selectively activates ALDH3a1, is safe to use in humans, and when given to mice, can preserve saliva function after radiation without tumor protection. Therefore, we propose to conduct additional animal studies to optimize the duration of Alda-341 treatment, the sequencing between Alda-341 and radiation therapy, and human studies to determine the distribution of the drug to salivary glands.

Transdermal deferoxamine to enhance fat graft retention for reconstruction of irradiated soft tissue defects - Derrick Wan, MD (Stanford University)

Soft tissue defects following cancer resection of the head and neck present a reconstructive challenge with substantial medical burden. Adjuvant radiation therapy can be highly effective at reducing local recurrence, however detrimental collateral changes including macroscopic discoloration, loss of skin elasticity, microscopic obliteration of small vessels, and dermal thickening make management difficult. To mitigate some of these changes and facilitate reconstruction of irradiated defects, we have developed a transdermal drug delivery system to provide sustained cutaneous delivery of deferoxamine, an FDA approved iron chelator for treatment of acute iron poisoning and chronic iron overload. Local iron chelation can also in increase revascularization of ischemic tissue, and we have already demonstrated local injection of this medication to reverse many hallmarks of chronic radiation-induced soft tissue injury. Our proposal seeks to evaluate the effectiveness of transdermal deferoxamine delivery to improve blood flow and skin biomechanics of irradiated tissue, as well as to determine the ability for our novel patch to improve fat graft based reconstructive strategies.

Peptide-impregnated hydrogel system for improving cleft lip and palate wound healing - Zhong Zheng, PhD (Scarless Laboratories)

Development of therapeutic suture devices that can accelerate the reestablishment of tensile strength in high risk, high tension wounds can significantly minimize wound dehiscence and hypertrophic scarring to improve functional and aesthetic outcomes. To this end, we have found that a fibromodulin-derived peptide (PGP) can significantly promote fibroblast migration and increase wound tensile strength in both rodent and pig models. Additionally, PGP-coated absorbable surgical sutures showed a 50% increase in wound tensile strength compared with control non-peptide-coated sutures in porcine models, which are preferred by the US FDA for testing human cutaneous products. Given the broad indication for surgical sutures, using a gel formulation that can be applied with any suture configuration may provide application flexibility and a streamlined manufacturing strategy for commercialization. Thus, the goal of the current C-DOCTOR ITP Team award is to develop and accomplish key efficacy objectives to expedite the commercialization of a peptide-impregnated gel-type device that can be applied with any suture configuration (with respect to needle specifications, suture composition, and size) for accelerating the reestablishment of tensile strength and minimizing wound dehiscence. If successful, this product can significantly improve the quality of life of patients suffering from poor wound healing or dehiscence.