Regenerative Medicine Resource Center - 2021 Annual Report by M Dentistry

2021 Annual Report

Letter from the Leadership As we look back on 2021, we share a great sense of gratitude for the many individuals who have relentlessly continued to support the Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center. Our project teams and advisors have remained nimble and adapted to new ways of conducting research and advancing technologies. We hope you enjoy this year’s annual report, highlighting new center-wide initiatives and achievements, as well as advancements of the individual Interdisciplinary Translational Projects (ITPs). These accomplishments are a testament to the resiliency and the continued commitment of the Resource Center members, project teams, advisors, sponsors, and all those who support our mission to bring promising tissue engineering and regenerative medicine technologies to the dental, oral and craniofacial clinical marketplace. Thank you for your continued support of the Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center. Sincerely, David Kohn, PhD | University of Michigan William Giannobile, DDS, DMedSc | Harvard University David Mooney, PhD | Wyss Institute Charles Sfeir, DDS, PhD | University of Pittsburgh William Wagner, PhD | University of Pittsburgh

Our Mission Our mission is to strategically partner with scientists, engineers and clinicians to translate dental, oral and craniofacial tissue engineering and regenerative medicine technologies to the clinical marketplace. We assist by building a customized approach for success utilizing an innovative toolkit, access to an exclusive mentorship and an expansive community of translational resources.

About the MPWRM Resource Center The Michigan-Pittsburgh-Wyss Regenerative Medicine (MPWRM) Resource Center is one of the two national Resource Centers established by the National Institute of Dental and Craniofacial Research (NIDCR)’s Dental Oral and Craniofacial Tissue Regeneration Consortium (DOCTRC) initiative, under Award Numbers U24DE026915 and U24DE029462. With the overarching goal of developing clinical trial-ready tissue engineering/ regenerative medicine products and protocols, the DOCTRC initiative provides funding and resources through the Interdisciplinary Translational Project (ITP) program administered by the two national Resource Centers.

The MPWRM Resource Center brings together a multidisciplinary team of clinicians, engineers, scientists, and technology commercialization and regulatory experts from academia and industry to support the regenerative medicine research community by providing resources and expertise to guide innovations that address unmet clinical needs for the regeneration or restoration of DOC tissues. Through the Core Services and Resources provided, the MPWRM Resource Center strives to accelerate the translation of promising technologies towards clinical trials and beyond.

Core Services and Resources In Vitro/ In Vivo Validation

Regulatory

microCT | Histology | Histomorphometry Biomechanics | Mechanical/ Functional Assessment Materials Fabrication & Characterization Pre-Clinical Animal Models and Testing

Identify and navigate the regulatory pathways; Assist in the implementation of design controls; Prepare and facilitate FDA submissions

Training Resources Assist in the translation of scientific discoveries into clinical practice; Cultivate multidisciplinary collaborations through stategic partnerships; Train the next generation of researchers to improve health outcomes for patients in need

Standardization | Quality Controls Provide input and tools as an approach to developing carefully planned studies; Serve as a resource to help interpret FDA requirements

Intellectual Property/ Commercialization Evaluate and analyze IP opportunities to strengthen proprietary position; Assist investigators to define and successfully achieve business milestones; Provide guidance on technology commercialization process

Market Assessment Support strategic decision making for new technology development by exploring market opportunities and current business trends

Prototyping | Manufacturing Cell/ Materials Characterization & Manufacturing Method and Process Development Drug Release Profiling www.mpwrm-doctrc.org

ITP Program in Numbers

96 14

Total number of Interdisciplinary Translational Projects

ACCELERATED

Total number of Applications Reviewed

Currently Active ITPs

The ITP program seeks to identify promising regenerative medicine/ tissue engineering technologies that address clear unmet clinical need with market potential in the dental, oral, and craniofacial (DOC) space, and to catalyze the clinical translation of these technologies towards FDA submissions. The long-term goal is to achieve high impact outcomes in the clinical marketplace.

Currently Active Interdisciplinary Translational Projects (n=13)

Tissues Addressed

Technology Type

Device Biologic Drug Cellular

92%

Bone Tooth Dental Implant Skin Muscle

Institution

Periodontal Salivary Gland Nerve TMJ

ITP teams with issued or pending patent/ applications

www.mpwrm-doctrc.org

External: for-profit Internal External

69% ITP teams with FDA submissions

Resource Center Impact

8 $15M 34

Follow-on grants and award recognitions

Follow-on funding (including grants and fundraising activities)

Number of external entities with whom ITP teams have established collaboration/ discussions and non-disclosure agreements

From the ITP teams... ... practitioner interviews with The Avenues were key to validating our commercialization plan. – Taboas / Ray team

Dental-specific market expertise has been very hard to find. The dental-specific expertise provided by the Resource Center has been very valuable. – Emergence Dental / nanoMAG team

It has been a tremendous learning curve on how to navigate quality controls, and we value all the details that go into an experiment requirement document as we prepare towards regulated studies, and compile documents for the FDA submission. Continue to provide the tremendous support!

The Resource Center has helped our team move marketing and regulatory efforts forward much faster. The help has been instrumental to the success of our project. – Rubin team

The interface between the Resource Center and RevBio has led to a very successful partnership since the development of a novel device requires a broad range of experts from quality assurance to regulatory affairs. In addition, the industry knowledge and market research capabilities of The Avenues Company have helped to further define the clinical need and elucidate the market potential for our product. Overall, the Resource Center and its internal resources have been critical in advancing the development of our product. – RevBio team

– Lombaert / Passineau team

www.mpwrm-doctrc.org

Year in Review

2020

December

2021

1st Joint DOCTRC retreat. MPWRM Resource Center and C-DOCTOR host a first joint annual retreat as a single consortium, DOCTRC (Dental, Oral, Craniofacial Tissue Regeneration Consortium). Held virtually, the retreat was attended by the membership of both centers and the respective ITP teams, as well as by NIDCR leadership and guests. The day consisted of poster presentations by the project teams, and breakout sessions to discuss how to increase the diversity of project PIs in the ITP program. Key retreat outcomes include programs for professional development and diversity, equity, and inclusion for members of the consortium.

January Translational Research Consult Program launched. The Translational Research Consult Program provides guidance in a particular translational research discipline as related to the development of a technology towards clinical implementation in the DOC space. The program provides an in-kind one-hour teleconference consultation with one of the MPWRM Resource Center’s experts, in response to information provided by the applicant through an online application process. Program is open to researchers world-wide. ITP team, Emergence Dental, joins AlphaLab Health program of Innovation Works. ITP team Emergence Dental is one of the inaugural cohort companies of AlphaLab Health, and closes a seed investment from AlphaLab Health.

www.mpwrm-doctrc.org

April MPWRM Resource Center publishes a white paper in Journal of Dental Research. Article provides providing generalized strategies and methods to support the translation of early-stage dental, oral, and craniofacial regenerative medicine innovations. Included is a translational development status questionnaire, a tool to assess the translational stage of a project and to build a roadmap towards FDA submissions. Editors of Journal of Dental Research, interview Resource Center PI, David Kohn, PhD (UMichigan) , to highlight the Center’s white paper publication. ITP Program Cycle 6 Request for Applications released. MPWRM Resource Center solicits an open request for applications for its ITP program. ITP team, GreenMark Biomedical, secures FDA clearance to market its LumiCare™ Caries Detection Rinse. Launch of the product took place at the National ADA show in Las Vegas in October 2021. ITP team, RevBio’s work with Tetranite highlighted by NIH. RevBio’s work with Tetranite® for local delivery of nonaddictive pain medicine funded by NIH’s HEAL initiative is highlighted on NIH website.

June MPWRM Resource Center hosts 3rd Annual Stakeholder’s Summit. This year’s event featured a panel discussion on successful clinical translation of innovations to product adoption in the oral regeneration market. Panelists included key opinion and industry leaders in the field, providing a robust discussion on the topic. Recording of the event can be viewed on our website. In addition, project teams and corporate attendees participated in a 1:1 speed networking event.

ITP team, Ostiio, is awarded a Phase I SBIR award from the America’s Seed Fund - National Science Foundation.

July C-DOCTOR and MPWRM Resource Center host a Symposium at the 2021 IADR/AADR/CADR General Session & Exhibition, entitled Clinical Translation of Tissue Engineering & Regenerative Medicine Technologies. – Jeanne Ambruster (The Avenues Company): “Right to left thinking optimizes clinical adoption” – Scott Fraser, PhD (University of Southern California): “Translating intravital imaging: bench to bedside and back” – Michael Jamieson, DRSc (Core Director, C-DOCTOR): “Three steps forward and two steps back: the importance of understanding the regulatory pathway” – Darnell Kaigler, DDS, MS, PhD (University of Michigan): “Overcoming challenges in the clinical translation of research” ITP PI, Kacey Marra, PhD (UPittsburgh), receives a DoD award. Kacey Marra, PhD, PI of an ITP, A Novel Conduit that Enhances Nerve Regeneration, is awarded a 2-year award of more than $2M from the Department of Defense to obtain regulatory approval for the novel nerve guide.

September ITP team, Ostiio, chosen to participate in the prestigious MassChallenge 2021 Accelerator cohort. From over 3,000 that applied, Ostiio was one of 221 companies from across the globe invited to participate. ITP team, GreenMark Biomedical’s LumiCare™ product is recognized as Cellerant Best of Class Technology Award for 2 years in a row.

October DOCTRC launches Innovator Network Series. As an outcome of the first joint DOCTRC retreat, the MPWRM Resource Center and C-DOCTOR launch an Innovator Networking Series to connect projects across the Consortium and to support the research community in the DOC space. Based on the poll of both Center’s ITP teams, this first session focuses on professional development, in particular, on academic entrepreneurship.

December 2nd Joint DOCTRC retreat. MPWRM Resource Center and C-DOCTOR host the second annual joint retreat as a single consortium.

August William Wagner, PhD (UPittsburgh), a Resource Center PI, is featured at International Space Station Research and Development Conference 2021, and discusses opportunities for biomanufacturing in space.

www.mpwrm-doctrc.org

RegendoGEL: A Bioinspired Hydrogel System for Endodontic Therapy Clinical Need Tooth damage, decay and eventual tooth loss is the clinical problem addressed by our product, RegendoGEL. Specifically, RegendoGEL will be used for vital pulp therapy. In contrast to currently used dental materials for tooth repair, RegendoGEL is a first-in-kind regenerative dental product for vital dental pulp and dentin regeneration. RegendoGEL will harness the regenerative properties of natural dental pulp to heal the tooth, by promoting natural dental pulp and dentin formation.

PamelaName Yelick, PhD TuftsSchool University

Luiz Bertassoni, DDS, PhD Oregon Health & Science University

Solution RegendoGEL is a hydrogel based material that contains bioactive molecules that promote natural tooth dental pulp and dentin formation. RegendoGEL is a first-in-kind regenerative dental product for vital dental pulp and dentin regeneration, intended to treat damaged teeth in a similar manner currently being used for synthetic, non-regenerative dental materials such as calcium and silicate cements and MTA.

Competitive Advantage

RegendoGEL is a first-in-kind regenerative biomaterial for vital pulp therapy, which contains natural tooth derived bioactive molecules that promote vital pulp and dentin regeneration. RegendoGEL is biocompatible, biodegradable and non-inflammatory, and repairs teeth up to 5X faster and better than currently used synthetic pulp therapy materials.

As compared to conventional rigid silicate or calcium hydroxide-based products, RegendoGEL will stimulate natural dental pulp and dental regeneration, repairing the tooth defect with natural, vital, dental tissues. RegendoGEL has been shown to accomplish this as much as 5 times faster than existing products in the market. Its biocompatibility, non-inflammatory, and degradable properties reverse the degenerative cycle of tooth repair, which normally progresses from a small cavity and filling, to larger fillings, eventually leading to endodontic treatments and replacement therapy such as dental implant or bridge.

ITP Support ITP support has been extensive. Business advice has been provided from the Regulatory Core, including the anticipated classification of RegendoGEL as Class II 510(k) product. Pre-clinical Animal Model Core conducted animal studies, and the micro-CT and histology Cores performed analyses of the harvested teeth, under guidance from the Statistical Core. Ongoing guidance on how to bring our product to the market has been provided by the Prototype & Manufacturing Core, and IP/ Commercialization Cores.

Clinical Translation Pathway

Publications: Khayat et al. GelMA-Encapsulated hDPSCs and HUVECs for Dental Pulp Regeneration. J Dent Res 2017 Parthiban et al. Engineering pericyte-supported microvascular capillaries in cell-laden hydrogels using stem cells from the bone marrow, dental pulp and dental apical papilla. Sci Rep 2020 IP: US16/618,329 Dental Pulp Constructs US15/777,304 Pulp Regeneration Compositions and Methods of Forming and Using the Same Anticipated regulatory pathway: IDE to enable 510(k) Anticipated commercialization strategy: New company formation, partnership for distribution Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center is supported in part by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Number U24DE026915 and U24DE029462. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

https://facultyprofiles.tufts.edu/ pamela-yelick www.bertassonilab.com

www.mpwrm-doctrc.org

Vital-Dent, A Revitalizing Root Canal Implant Clinical Need Dentist in the USA perform approximately five million procedures per year to treat pulpitis in the pediatric population (5-19 years old). Children are subject to multiple procedures attempting to conserve their permanent immature teeth because most therapies are not regenerative, suffering tooth discoloration, loss of tooth structure, and limited (if any) tooth growth. Definitive treatment is often postponed until the child’s growth stops. Therefore, dentists, parents, and insurers desire a commercial product to treat irreversible pulpitis and improve the outcomes of current pulp therapies in children.

Solution

Juan Taboas, PhD University of Pittsburgh

Herb Ray, DMD

University of Pittsburgh

Vital-Dent is an acellular, drug-free, off-the-shelf implantable device to regenerate tooth pulp and maintain vitality of immature permanent teeth treated with endodontic therapies (a.k.a. root canal treatment, RCT). It is a colorless hydrogel supplied as powder in a syringe kit. The dentist rehydrates Vital-Dent with saline in the kit. They then apply the hydrogel into the instrumented canal space as they would conventional canal obturation. The hydrogel set in three minutes with a dental curing lamp and the tooth is sealed with a bioceramic. Restoration follows conventional methods.

Competitive Advantage Unlike commercially available materials, Vital-Dent is resorbable and promotes continued tooth development, pulp and dentin regeneration, root strengthening, and long-term survival of the tooth. The only regenerative therapy (revascularization) fills the instrumented tooth with a blood clot or other autologous blood product, but is more difficult to implement and has variable outcomes with no definitive implant material. Vital-Dent better fits conventional clinic workflows and yields better outcomes with less canal calcification.

ITP Support We have planned a product portfolio in regenerative endodontics, a marketplace estimated at $3B with no leader. With help from the Market Assessment Core, we defined the indication for market entry as pulpectomy of irreversible pulpitis in 10-15 year olds. We filed patent applications with IP analysis with the IP/ Commercialization Core. We froze the device composition and completed a large-scale demonstration of safety and efficacy in a dog model of pulpectomies with the Regulatory Core. We identified a regulatory path with and are working on an FDA request for designation. We established relationships with VC firms and dental suppliers, all advancing commercialization.

…so we are trying to do whatever is possible to save the tooth first – Parent of a patient seeking Vital-Dent

Clinical Translation Pathway

Publications: Zaky et al. Effect of the Periapical “Inflammatory Plug” on Dental Pulp Regeneration: A Histologic In Vivo Study. J Endod 2020 Vieira et al. Pediatric Endodontic Treatment of Adolescent Patients. Dent Clin North Am 2021 IP: PCT/US2019/023132 Regeneration of Vital Tooth Pulp Anticipated regulatory pathway: Class II device Anticipated commercialization strategy: Plan formation of a start-up company Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center is supported in part by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Number U24DE026915 and U24DE029462. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

www.mpwrm-doctrc.org

www.dental.pitt.edu/people/ juan-m-taboas-ms-phd

Targeted Remineralization Treatment Using Mineral Loaded Starch Nanoparticle Clinical Need

Steven Bloembergen, PhD GreenMark Biomedical Inc.

Over $200 Billion is spent globally on dental caries and its complications, the most prevalent chronic disease worldwide. Disease management is moving away from surgical to a more medical approach, but the challenge is that there are no effective ways to monitor treatment success, and there are no FDA-approved nonsurgical caries treatments. Off-label methods include professionally applied fluoride varnishes, prescription and OTC fluoride toothpastes, and calcium phosphate remineralization agents. However, these are unable to regenerate enamel within the depth of subsurface carious lesions.

Solution Small fluoride and mineral-loaded starch particles have been developed by GreenMark Biomedical Inc. and its University of Michigan collaborators for treatment of non-cavitated carious lesions. These particles have been designed for targeted delivery to the enamel subsurface. Two caries-targeting products have emerged, one based on fluoride free mineral-loaded particles, and its fluoride-containing analog. Subsurface remineralization was demonstrated for both using enamel density measurements, as well as the occlusion of dentinal tubules, key to treatment of dentinal hypersensitivity.

Competitive Advantage Targeted regeneration of enamel will allow for more natural repair of dental caries using painless and non-invasive treatment, reducing discomfort during dental procedures, preserving dental tissue and improving long term oral health of patients.

While traditional fluoride treatments merely impact the extreme surface layer of enamel lesions, targeting to the dominant subsurface lesion is expected to enable a superior non-surgical dental treatment. High localized concentration of minerals and fluoride is expected to facilitate tooth structure regeneration through formation of hydroxyapatite-like crystals, yielding superior remineralization of lesions compared to other available treatments.

ITP Support The support from the ITP program has helped advance the technology with access to critical expertise and facilities, continued technical, regulatory, clinical and marketing validation.

Clinical Translation Pathway

Publications: Jones et al. Nanoparticle-based targeting and detection of microcavities. Adv Healthc Mater 2017 Targeted Enamel Remineralization with Mineral-Loaded Starch Particles. IADR 2021 IP: US10,987,434 Detection and Treatment of Caries and Microcavities with Nanoparticles Anticipated regulatory pathway: De Novo 510(k) Class II (tooth structure regeneration) Anticipated commercialization strategy: Direct sales force currently being developed by GreenMark for LumiCare™ product, complemented with distribution agreements with global strategic partner(s). Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center is supported in part by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Number U24DE026915 and U24DE029462. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

https://greenmark.bio

www.mpwrm-doctrc.org

Abaloparatide to Treat Alveolar Bone Loss for Dental Implant Reconstruction Clinical Need It is estimated that 2 million patients receive dental implants in the U.S. annually and up to 50% are post-menopausal women with osteoporosis. Dental implants are a highly efficacious treatment modality for tooth loss, but osteoporosis patients may be denied implant therapy due to concerns regarding bone quantity and quality. Predictable treatments to arrest and regenerate lost tissues around teeth and/or tooth-replacing dental implants are limited, and to date, there are no FDA-approved bone anabolic agents available to treat periodontal or peri-implant bone loss.

Solution A team of researchers led by Dean William Giannobile at the Harvard School of Dental Medicine is investigating the therapeutic potential of a systemic osteoanabolic drug, abaloparatide, to restore lost periodontium or enhance formation of implant-supporting alveolar bone. This approach offers easy dosing to regenerate lost periodontium or improve peri-implant bone density.

William Giannobile, DDS, DMedSc Harvard University

Competitive Advantage By taking advantage of easy delivery of abaloparatide, which is already clinically approved for improvement of bone density in other indications such as osteoporosis, this approach may represent an improved access to drug therapies for periodontal and dental implant-related diseases that might otherwise not be as available due to limited reimbursement through typical dental insurance.

ITP Support The work supported by the ITP program is focused on the progression to a phase I/II human clinical trial to use on-label systemic abaloparatide to adjunctively treat alveolar bone loss and enable implant treatment for patients with compromised bone quality.

Clinical Translation Pathway

Publications: Christiansen et al. Bone mineral density response rates are greater in patients treated with abaloparatide compared with those treated with placebo or teriparatide: Results from the ACTIVE phase 3 trial. Bone 2019 IP: US10,568,937 Formulations of Abaloparatide, Transdermal Patches Thereof, and Uses Thereof Anticipated regulatory pathway: FDA-approved since 2017; no new IND required for dental implant study in on-label osteoporosis patients Anticipated commercialization strategy: In development with the MPWRM Commercialization/ Market Needs Core and Radius Health.

This novel technology offers systemic bone anabolic drug delivery to promote the regeneration of bone lost due to periodontal disease or dental implants needing bone reconstruction.

Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center is supported in part by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Number U24DE026915 and U24DE029462. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

https://hsdm.harvard.edu/ giannobile-laboratory

www.mpwrm-doctrc.org

Immunomodulatory Strategies to Treat Periodontal Disease Clinical Need

Steven Little, PhD University of Pittsburgh

Charles Sfeir, DDS, PhD

University of Pittsburgh

Periodontitis is one of the most pressing oral health concerns today, affecting nearly half of adults over age of 30 in the U.S. When left untreated, patients may require dental implants and bone grafting procedures. Antibiotics (killing of bacteria) are currently used as an adjunct therapy to scaling and root planing, which remain the current gold standard of care for periodontitis. However, with all medical practice shifting away from the overuse of antibiotics, new treatment modalities that address the host immune response responsible for most of the damage and disease progression are needed.

Solution A team at the University of Pittsburgh led by Dr. Steven Little (PI) and Dr. Charles Sfeir, DDS (co-I) has developed non-antibiotic, controlled release microparticle systems that repair the underlying immunomodulation dysfunction responsible for tissue degeneration in periodontitis. The formulation recruits regulatory T cells to induce homeostasis and thereby reduce inflammation and destruction to promote tissue regeneration.

Competitive Advantage By targeting the underlying immunoregulatory discourse in periodontitis (a treatment strategy that is disparate to current antibiotic adjunct therapy), a controlled release system is thought to overcome the current limitation in the treatment of periodontal diseases.

This new class of treatments is extremely exciting in that organizing extraordinarily tiny amounts of proteins that are already found in the body seem to be capable of influencing the body’s own cells to repair the destructive inflammation that produces periodontal disease. To give perspective, it is possible to deliver millions of times less drug and achieve a better effect than the current gold standard.

ITP Support The goal of the work under the ITP program is to develop GMP-grade manufacturing and sterilization protocols to produce quality-controlled product for pharmacokinetic testing and toxicology studies in support of an FDA submission.

Clinical Translation Pathway

Publications: Glowacki et al. Prevention of Inflammation-Mediated Bone Loss in Murine and Canine Periodontal Disease via Recruitment of Regulatory Lymphocytes. Proc Natl Acad Sci USA 2013 Garlet et al. Restoring Host-Microbe Homeostasis via Selective Chemoattraction of Tregs. J Dent Res 2014 IP: US8,846,098 Artificial Cell Constructs for Cellular Manipulation Anticipated regulatory pathway: IND Anticipated commercialization strategy: In development with MPWRM Cores Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center is supported in part by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Number U24DE026915 and U24DE029462. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

www.littlelab.pitt.edu https://www.dental.pitt. edu/people/charles-ssfeir-dds-phd 10

www.mpwrm-doctrc.org

Optimization of a Novel Organic-Mineral Bone Adhesive for Dental Bone Grafting Clinical Need Based on market research conducted by RevBio, almost half the patients that seek a dental implant supported crown suffer from chronic edentulism and require extensive bone grafting to rebuild their alveolar ridge. Over 30% of the time, these grafting procedures achieve less than desired results and require some form of re-grafting adding to the overall cost, treatment time, and morbidity for these patients.

Solution Tetranite® (TN) is a synthetic, injectable, cohesive organic-mineral bone scaffold with adhesive properties that resorbs and is replaced by bone on a timescale commensurate with existing graft materials but does not require ancillary fixation (screws, tacks) or containment devices (membranes, mesh). The Tetranite Dental Adhesive Bone Scaffold (TN-ADBS) product comprises of a kit consisting of (a) the formulation powders and granules sealed in a mixing bowl, (b) aqueous medium pre-filled syringe, (c) a spatula and (d) delivery system that is sourced as an off-the-shelf syringe.

Joseph Fiorellini, DMD, DMSc

University of Pennsylvania

George Kay, DMD, MMSc RevBio

Competitive Advantage Currently available particulate bone grafting products require significant surgical skill to apply. In contrast, TN-ADBS is a flowable biomaterial that is both cohesive and adhesive which enables the placement of the product without the ancillary containment and fixation aids. The product will reduce the overall time necessary to conduct ridge augmentation procedures, better maintain graft volume over time, and minimize the need for re-grafting, which adds time, cost, and risk to successful patient care.

ITP Support ITP support has enabled RevBio to accomplish key product development and marketing milestones, including market survey to validate the clinical need and a lack of any known competitive products with comparable clinical value proposition, refinement of preclinical animal model and product formulation, GLP preclinical studies and supplier audits, provision of advice on user handling trials, and regulatory guidance in developing and refining a cohesive strategy for the commercial approval of the product.

Clinical Translation Pathway

Publications: Brown et al. From bench-to-bedside: Licensing and development of a mineral-organic bone adhesive for bone repair. Transactions of the Annual Meeting of the Society for Biomaterials and the Annual International Biomaterials Symposium 2019 Taylor et al. Translating Dental, Oral, and Craniofacial Regenerative Medicine Innovations to the Clinic through Interdisciplinary Commercial Translation Architecture. J Dent Res 2021 IP: US8,232,327, US8,273,803 Tetracalcium Phosphate Based Organophosphorus Compositions and Methods US8,765,189 Organophosphorous & Multivalent Metal Compound Compositions and Methods Anticipated regulatory pathway: Device-led combination product Anticipated commercialization strategy: In development

The Resource Center has been an excellent collaboration between NIDCR, academia and industry. Not only does the collaboration foster the development of a clinical product but also accelerates the process. From histology core services to regulatory advice, the Center has worked hand in hand with us to ensure not only first-class science but development of the program for other investigators. All in all, this has been one of the most enriching processes in my time in translational research.

www.revbio.com

www.mpwrm-doctrc.org

Customizable CMFlex™ Bone Grafts for Craniomaxillofacial Bone Defect Applications Clinical Need

Ramille Shah, PhD Dimension Inx

Craniomaxillofacial (CMF) bony defects are challenging to reconstruct. Autologous bone grafting remains the gold standard, but donor site morbidity, surgical complications at the donor site, scarcity of donor tissue, and the time and skill set needed to shape into irregular defects can be limiting. Alternatives such as synthetic or allograft bone chips, granules, or putties are used but can migrate from the defect, inhibit tissue integration due to limited porosity, and increase infection risk. These drawbacks emphasize the significant need for better biomaterial solutions.

Solution Our intended product is a 3D-printed bone graft, CMFlex™, that possesses a hierarchically porous structure made up of a majority calcium phosphate (CaP) and minority poly(lactide-co-glycolide) (PLG) with the following measurable benefits: osteoregenerative, safe, shape and volume maintaining, surgically-friendly (i.e., pliable enough to be press fit into defects and easily cut/shaped while maintaining structural integrity), manufacturable and scalable, and commercially viable (i.e., acceptable price point).

Competitive Advantage Unlike other synthetic bone grafts used for these indications, the use of 3D-printing to manufacture CMFlex™ imparts several advantages: 1) a distinct, inherent nano/microstructure that is responsible for much of the product’s unique properties (e.g., pliable yet made of mostly osteoconductive ceramic), 2) enables a 3D interconnected porous structure ideal for protein adhesion, cell migration, and tissue integration, and 3) permits future form factors (including patient-specific) to be rapidly designed and implemented. .

ITP’s support will help us develop transformative biomaterials that address critical needs in treating CMF deficiencies.

ITP Support ITP program will support continued market development efforts for CMFlex™.

Clinical Translation Pathway

Publications: Jakus et al. Hyperelastic “Bone”: A Highly Versatile, Growth Factor-Free, Osteoregenerative, Scalable, and Surgically Friendly Biomaterial. Sci Transl Med 2016 Huang et al. 3D-Printed “Hyperelastic Bone” Scaffolds Accelerate Bone Regeneration in Critical-Sized Calvarial Bone Defects. Plast Reconstr Surg 2019 IP: US10,584,254 Ink Compositions for Three-Dimensional Printing and Methods of Forming Objects Using the Ink Compositions US15/963,348 Ceramic-Containing Bioactive Inks and Printing Methods for Tissue Engineering Applications Anticipated regulatory pathway: 510(k) Anticipated commercialization strategy: Develop products until ready for commercialization and then partner with strategics for marketing, sales, and distribution. Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center is supported in part by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Number U24DE026915 and U24DE029462. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

www.dimensioninx.com

www.mpwrm-doctrc.org

AmpliMag Mesh and Mesh Fixation System Clinical Need Over one million dental bone grafting procedures are performed annually in the US, most frequently before dental implant placement. In the most challenging grafting procedures, where there is a significant vertical deficit, even expert clinicians face revision rates reaching 25% due to the difficulty of reliably regenerating sufficient bone for implant placement. Currently used barrier membranes, meshes and fixation systems are unable to offer the form-stability needed to protect healing grafting sites from mechanical insults, while also offering resorbability and gingival tissue friendliness. The inability of regenerative products to offer these three features result in dental bone grafting procedures that are highly technique-sensitive, prone to adverse events, and require invasive removal procedures.

Solution

Andrew Brown, PhD

Stephen LeBeau, PhD

Emergence Dental

nanoMAG

The AmpliMag Bone Grafting System provides the form-stability and gingival-tissue friendliness needed to minimize adverse events and maximize bone regeneration. The system is fully resorbable which eliminates the need to retrieve hardware following healing. The AmpliMag system is based on a patented magnesium alloy developed by nanoMAG and device designs developed at the University of Pittsburgh.

Competitive Advantage No other barrier membranes or meshes offer both form-stability and resorbability which, taken together, enable maximization of alveolar ridge augmentation while obviating the need for device removal.

ITP Support The ITP program has provided financial support for design, manufacturing, and benchtop and pre-clinical testing activities for the AmpliMag barrier membrane. Additionally, the Resource Center has provided expert clinical, market, regulatory, and quality advice.

Clinical Translation Pathway

Publications: Brown et al. Porous magnesium/PLGA composite scaffolds for enhanced bone regeneration following tooth extraction. Acta Biomater 2015 IP: US10,022,470 High Strength and Bio-Absorbable Magnesium Alloys PCT/US2019/018545 Improved Magnesium Alloy and Process for Making the Same Anticipated regulatory pathway: Device, 510(k) as 2 separate products (mesh/ fixation system) Anticipated commercialization strategy: Emergence Dental, Inc. will partner with an existing dental regenerative or implant company on clinical adoption studies and distribution activities.

Emergence Dental was founded to combine biomaterial intellectual property from nanoMAG and University of Pittsburgh to address unmet needs in dental bone regeneration. The Resource Center has enabled us to accelerate the development of the AmpliMag Mesh and Fixation System not just with funding, but with expertise that we have not been able to access elsewhere.

www.nanomag.us www.emergencedental.com

www.mpwrm-doctrc.org

Ostiio: A Smart, Fully-Implantable CMF Distractor Clinical Need Each year >200K newborns suffer from conditions that restrict growth of the skull or jawbone. Left untreated these can have life threatening outcomes in an otherwise healthy child. However, treatments are complex and traumatic. Distraction is a gentler therapy that uses a device to slowly expand abnormal bone, but: 1) distractors are semi-buried, increasing complication risk; 2) manual expansion is performed by parents, leading to noncompliance; 3) surgeons are blinded to treatment, forcing weekly x-rays & exams.

Ari Wes, MD Ostiio LLC

Solution Ostiio’s integrated therapy uniquely solves pain points of distraction to improve patient outcomes and experience while reducing cost. 1) The fully buried implant is magnetically expanded without contact, removing the complication risk of semi-buried devices. 2) The automated driver simplifies expansion to a button push, reducing parental noncompliance. 3) The remote monitoring platform allows surgeons to track treatment progress and address complications early on, reducing post-op follow-up.

Competitive Advantage Although distraction is the segment within the craniomaxillofacial device market that offers differentiation opportunity, major competitors have been focused on iterating upon the same basic technology that was first introduced to market >20 years ago to provide greater flexibility to the surgeon in the operating room. But treatment takes place at home. Ostiio instead is focused on transforming how distraction is provided by parents and monitored by surgeons to improve patient outcomes and experience while reducing cost.

Unlike typical grants, ITP enables productization, allowing us to bring our life-altering tech a step closer to reality.

ITP Support The ITP program has enabled Ostiio to advance its integrated therapy from the early prototyping phase into a formal, staged product development process. Working within a quality management system, Ostiio has developed functional, working prototypes that exceed the most critical product specification by more than 2.5 times. In parallel, Ostiio has been able to initiate key regulatory activities and complete important market validation work.

Clinical Translation Pathway

Publications: Zhang et al. Evaluation of parental and surgeon stressors and perceptions of distraction osteogenesis in pediatric craniofacial patients: a cross-sectional survey study. Childs Nerv Syst 2018 Zapatero et al. A quantification of scalp thickness pre- and post-posterior vault distraction osteogenesis. Plast Reconstr Surg (manuscript accepted) IP: PCT/US2018/021269 Systems and Methods for Contactless Craniomaxillofacial Distraction PCT/US2020/017918 Systems and Methods for a Smart, Implantable Craniomaxillofacial Distractor Anticipated regulatory pathway: Class II medical device via 510(k) pathway Anticipated commercialization strategy: Pilot therapy in influential centers and leverage these KOL relationships to drive awareness Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center is supported in part by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Number U24DE026915 and U24DE029462. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

https://ostiio.com

www.mpwrm-doctrc.org

Non-Viral Aquaporin1 Gene Therapy to Restore Salivary Flow Clinical Need In the treatment of head and neck cancers, radiotherapy is commonly executed in conjunction with other modalities, such as surgery and/or chemotherapy. Because of the anatomical proximity, salivary glands receive secondary radiation damage, which results in xerostomia. While intensity-modulated radiotherapy significantly reduces the incidence of radiation-induced xerostomia, a need still exists for patients suffering from xerostomia, especially those in whom amifostine leads to significant side effects.

Solution The method of ultrasound-assisted gene transfer (UAGT) was developed to deliver the AQP1 gene in irradiated salivary gland for the amelioration of radiation-induced xerostomia. This non-viral gene delivery is based on sonoporation generated by the ultrasound, enabling gene transfer into radiation-surviving salivary gland cells. The delivery of the water channel AQP1 to the parotid glands in a mini-swine model restored salivary flow post-radiation to pre-treatment levels, demonstrating the efficacy of our non-viral AQP1 gene transfer approach.

Michael Passineau, PhD Allegheny Health Network

Isabelle Lombaert, PhD University of Michigan

Competitive Advantage While a recent clinical trial using a viral-based AQP1 gene delivery demonstrated an increase in saliva production, this approach has not advanced beyond a successful Phase I/II trial due to side-effects generated by the adenovirus vector. With our non-viral based approach, it is anticipated that enhanced safety is provided and that serial dosing is feasible to provide patients with AQP1 gene therapy throughout their lifetime.

ITP Support The long-term objective of this research program is to improve the quality of life in patients who suffer from radiation-induced xerostomia. Through the ITP support, the team has demonstrated the safety of the UAGT method, and collected data on the efficacy of UAGT for the delivery of AQP1 gene therapy towards enabling FDA submission.

Clinical Translation Pathway

Publications: Wang et al. Ultrasound-assisted nonviral gene transfer of AQP1 to the irradiated minipig parotid gland restores fluid secretion. Gene Ther 2015 IP: In development Anticipated regulatory pathway: Biologic; IND to enable BLA Anticipated commercialization strategy: New company formation/ license to industry partners

We aim to develop a safe and non-viral gene therapy approach to provide lifelong relief of xerostomia in head-and-neck cancer patients whose salivary function is affected by radiation therapy.

https://media.dent.umich.edu/ labs/lombaert

www.mpwrm-doctrc.org

Tissue Engineering Functional Human Lips Clinical Need The intended product assists in the repair/ regeneration resulting from traumatic avulsion injuries or secondary to cancer ablative surgery involving a sphincter/stoma/lumen/opening that result in loss of volumetric muscle mass and function in the body such as the face (lips, eyelids) and urogenital tract (anal sphincter, vagina).

Stephen Feinberg, DDS, PhD University of Michigan

Solution The product consists of a pre-fabricated innervated (motor nerve) pre-vascularized pre-laminated (PIPP) composite “designer” soft tissue microvascular free flap, based on latissimus dorsi muscle (LDM), that is composed of autogenous oral-skin-dermis-muscle that can be used in functional reconstruction of human lips. The in vitro produced muco-cutaneous “laminate” is composed of autogenous oral and skin keratinocytes cultured on an acellular dermal matrix, and is placed on LDM using the body as an “in situ bioreactor” to finalize the tissue engineering medical product. The stoma/opening in the PIPP flap is maintained with a proprietary biocompatible obturator.

Competitive Advantage There are no other competitive products on the market. The gold standard is the radial forearm free flap with the palmaris longus tendon, which creates an immobile, stiff lip, or an allogeneic cadaver graft that requires immunosuppression. The ultimate source of the cells to develop the soft tissue constructs (lips), PIPP, will come from the patient, thus making the construct autochthonous (self to self) and obviates the need for immunosuppression seen with allogeneic grafts.

Our goal is to establish a platform technology to create a paradigm shift in functional reconstruction of composite soft tissues with a mucocutaneous junction, containing a stoma/ opening/lumen.

ITP Support ITP has supported the creation of an autogenous mucocutaneous construct to use as a laminate for the PIPP flap, development and fabrication of a biocompatible proprietary obturator to maintain the stoma opening, and the development of an athymic rat model for use in preclinical GLP studies. Regulatory guidance and consultation for preparation of an IND submission to the FDA for a first-in-human clinical trial are supported by the program.

Clinical Translation Pathway

Publications: Peramo et al. Tissue Engineering of Lips and Muco-Cutaneous Junctions: In Vitro Development of Tissue Engineered Constructs of Oral Mucosa and Skin for Lip Reconstruction. Tissue Eng Part C Methods 2012 Kuo et al. Principles of Soft Tissue Engineering for Craniomaxillofacial Reconstruction. In: Melville J., Shum J., Young S., Wong M. (eds) Regenerative Strategies for Maxillary and Mandibular Reconstruction. Springer, Cham. IP: US PRV Obturator, Methods of Forming a Prefabricated, Innervated, Pre-Vascularized, Prelaminated (PIPP) Flap Using an Obturator to Maintain a Stoma or Lumen, and Methods of Restoring Damaged or Surgically-Removed Soft Tissue with A PIPP Free or Rotational Flap. Anticipated regulatory pathway: Combination product through a single IND/BLA pathway Anticipated commercialization strategy: In development Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center is supported in part by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Number U24DE026915 and U24DE029462. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

www.mpwrm-doctrc.org

Tough Adhesive for Oral Wound Care Clinical Need Bandages are commonly used for epidermal wounds, but an effective and easy to apply wound care product that stays in place to protect an oral wound does not exist. Unprotected wounds in the mouth can be a source of discomfort, pain, and infection. Application of Tough Adhesive over these wounds will greatly enhance patient comfort and oral wound care.

Solution Tough Adhesive is a hydrogel-based adhesive comprised of two primary elements. The hydrogel consists of an interpenetrating network of alginate and polyacrylamide. The adhesive is composed of chitosan, which forms covalent bonds across the interface. When used together, the hydrogel and adhesive adhere to wet tissue and provide over five times the adhesion energy of cyanoacrylate while also providing a long duration mechanical barrier for the wound and flexibility to stretch with the wound without damaging the underlying tissue.

Jamie Murbach, PhD Amend Surgical, Inc.

Competitive Advantage There are limited products available that will safely adhere to sutured or non-sutured oral wounds. Periacryl, a cyanoacrylate-based product indicated as a dental cement, is often used off-label for wound closure. It requires a dry environment to fully set and is rigid, not stretching to accommodate movement or swelling. Tough Adhesive adheres to tissue in a wet environment, stretches with the wound, and stays in place for weeks, allowing wound healing to occur.

ITP Support The ITP program will support design and development activities including evaluation of sterilization modalities, modifications of the Tough Adhesive technology to the challenges of the oral environment, evaluation of toxicological risks, and execution of a canine animal study to evaluate wound healing and removal of test articles. This program will provide our business with financial assistance, clinical expertise, and market and regulatory guidance leading up to FDA pre-submission.

Clinical Translation Pathway

Publications: Li et al. Tough Adhesives for Diverse Wet Surfaces. Science 2017 Yang et al. Topological adhesion of wet materials. Adv Mater 2018 IP: US11,033,658 Interpenetrating Networks with Covalent and Ionic Crosslinks PCT/US2019/055779 Bio-Inspired Degradable Tough Adhesives for Diverse Wet Environments Anticipated regulatory pathway: 510(k) Anticipated commercialization strategy: Upon FDA clearance, a post-market multisite clinical study will be initiated. Marketing and sales communications will focus on patient comfort.

Tough Adhesive protects oral wounds and improves wound healing and patient comfort.

https://amendsurgical.com

www.mpwrm-doctrc.org

Extracellular Matrix Scaffold for TMJ Disc Repair Clinical Need Removal of the Temporomandibular Joint (TMJ) disc is often the only option for surgeons to relieve symptoms (increase movement). However, this procedure leaves the patient with bone-on-bone contact that can lead to further degeneration of the joint. After TMJ disc removal, most surgeons do not replace it since there are no available alloplastic products. A few try autologous tissue replacements with muscle, or dermis, or fat grafts, but these have been shown to resorb within a year.

Alejandro Almarza, PhD University of Pittsburgh

Solution The TMJ Repair Graft is a fully developed, implantable extracellular matrix (ECM)-based device composed of porcine small intestine submucosa matrix developed by researchers from the McGowan Institute for Regenerative Medicine and surgeons from the Department of Oral and Maxillofacial Surgery at the University of Pittsburgh. This device has been developed to replace the disc of the temporomandibular joint (TMJ) by inducing the formation of new, patient specific, functional tissue formation.

Competitive Advantage

This technology will provide an off-the-shelf solution for the repair of the TMJ disc.

ECM device has been tailored to meet customer needs: • ECM device is an “off-the-shelf” product • ECM device is easily implantable without extensive training or changes in the current surgical paradigms • ECM device can be manufactured in multiple shapes and sizes to accommodate differences in patient joint size and shape ECM device improves patient outcomes: • Provides a temporary cushion for the TMJ, avoiding the wear and tear prevalent in current treatment options • Prevents degenerative changes to bones • Provides a template for new, host tissue formation

ITP Support In preparation for submission of a pre-IDE application to the FDA, the ITP program has supported the evaluation of the safety of the GMP device in a GLP animal study at the acute timepoint of 21 days. We have now shown that the GMP device is safe as seen by no adverse response in the surrounding tissue in the histopathological analysis. Furthermore, there was a lack of negative findings for clinical pathology, mortality, and body weight/weight change.

Clinical Translation Pathway

www.engineering.pitt.edu/TMJ

Publications: Brown et al. Extracellular matrix as an inductive template for temporomandibular joint meniscus reconstruction: a pilot study. J Oral Maxillofac Surg 2011 Brown et al. Inductive, scaffold-based, regenerative medicine approach to reconstruction of the temporomandibular joint disk. J Oral Maxillofac Surg 2012 IP: US9,314,340 Joint Bioscaffolds Anticipated regulatory pathway: Anticipated: Device, IDE to enable PMA Anticipated commercialization strategy: License technology after first-in-human trial Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center is supported in part by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Number U24DE026915 and U24DE029462. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

www.mpwrm-doctrc.org

A Device to Preserve Adipose Tissue Grafts for Soft Tissue Reconstruction Clinical Need Soft tissue deformities and volume/ contour deformities from craniofacial trauma, congenital anomalies, and cancer treatment are difficult to correct. Current standard of care includes injectable fillers, implants, and soft tissue flap procedures, which have limitations and often involve operations with significant risk. As such, autologous fat transfer is being explored as a lower risk alternative. However, as optimal results with fat transfer often require at least two treatments, there is a need for an on-site preservation of harvested tissue for subsequent procedures to minimize donor site morbidity and encourage fast recovery.

Solution A team of researchers at the University of Pittsburgh led by Dr. Peter Rubin has previously validated the use of autologous fat transfer as a minimally invasive therapy for the restoration of craniofacial form. In order to facilitate fat transfer with minimal donor site morbidity, the team has developed a novel device to cryopreserve adipose for storage at the treatment facility, which can directly be used for the subsequent fat transfer(s).

J. Peter Rubin, MD, FACS

University of Pittsburgh

Competitive Advantage With the on-site cryopreservation and storage of the fat tissue, the device is envisioned to reduce patient and clinician burden for tissue harvest. The utilization of the device obviates the need for repeat tissue grafting procedures, and is anticipated to lead to reduction in treatment costs as the fat transfer injections may be performed outside of an operating room in a less acute setting.

ITP Support The work supported by the ITP program is focused on the generation of a prototype cryopreservation/ storage device that can be used for clinical trials. Towards that end, project plans include prototype development and validation, as well as the development of a regulatory strategy and commercialization plan.

Clinical Translation Pathway

Publications: Kokai et al. Optimization and Standardization of the Immunodeficient Mouse Model for Assessing at Grafting Outcomes. Plast Reconstr Surg 2017 IP: PCT/US2018/049083 Method and Kit for Preservation of Adipose Tissue Grafts Anticipated regulatory pathway: Device, 510(k) Anticipated commercialization strategy: In development with the MPWRM Commercialization/ Market Assessment Core

The ability to easily and inexpensively store tissue on-site will result in significant decrease in patient discomfort and risk, as well as significant decrease in surgeon time spent on the repeat procedure.

https://plasticsurgery.pitt.edu/ research/research-labs/ adipose-stem-cell-center-ascc

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Towards a Sustainable Future Formally launched in March 2017, the Michigan-PittsburghWyss Regenerative Medicine Resource Center continues to shepherd promising regenerative medicine technologies towards initiation of clinical trials, commercialization, and ultimately clinical adoption. In collaboration with our sister resource center, C-DOCTOR (Center for Dental, Oral, & Craniofacial Tissue & Organ Regeneration), and our sponsor, National Institute of Dental and Craniofacial Research (NIDCR), we have developed a unique consortium that is now a proven model for catalyzing the translation of regenerative medicine technologies. We have forged strategic partnerships, built infrastructure, and provided expertise to support over 20 Interdisciplinary Translational Projects (ITPs). The MPWRM Resource Center brings together driven investigators and a network of capabilities and talent committed to the translation of technologies to products under one umbrella, to accelerate the clinical translation of promising dental, oral, and craniofacial regenerative therapies. As a supporter of the Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center, you will get an early view of cutting edge research and product development efforts for regenerative therapies in the dental, oral, and craniofacial space. Our portfolio of ITPs represents a curated compilation of active regenerative medicine approaches selected by the Resource Center based on compelling clinical need and commercial potential. Technologies are advanced by teams from prestigious academic institutions and startup companies, in close collaboration with the expertise and support of the Resource Center. You will be invited to help shape the future of the Resource Center and translation of

dental, oral, and craniofacial regenerative medicine technologies through opportunities to participate in and sponsor Resource Center events. These include our annual and semi-annual retreats, which bring together researchers, Resource Center experts, and guests who share a common passion in advancing regenerative technologies for the treatment of dental, oral, and craniofacial tissues. The Michigan-Pittsburgh-Wyss Regenerative Medicine Resource Center is a national center with a mission to serve the larger dental, oral, and craniofacial community beyond the ITPs we support. By expanding our impact beyond the MPWRM Resource Center members, we aim to strengthen our value and relevance to the broader community. The network of specialized expertise and the infrastructure of the MPWRM Resource Center is truly unique, with an unmatched combination of intellectual power and assets specific to the dental, oral, and craniofacial space. In a challenging economic time with a low risk tolerance for investing in early/ new innovations, a well-connected enterprise with a corresponding financial wherewithal is essential to enable high risk/ high reward projects of value. With your support, the MPWRM Resource Center will thrive as an attractive opportunity for not only financial investments but also for strategic partnerships to enable a sustainable innovation ecosystem that reaps long-term value in positively impacting patient lives. For more information on how to engage with our community, please contact us at MPWRMResourceCenter@umich.edu.

www.mpwrm-doctrc.org

Operating Committee The MPWRM Resource Center is governed by an Operating Committee, which is charged with providing strategic leadership and oversight for the Resource Center. The Operating Committee also prioritizes and selects Interdisciplinary Translational Projects (ITPs) to be supported by the Resource Center, in concert with NIDCR.

Jeanne Ambruster The Avenues Company Albert Donnenberg, PhD University of Pittsburgh Kay Fuller, RAC Medical Device Regulatory Solutions LLC William Giannobile, DDS, DMedSc Harvard University Steven Goldstein, PhD University of Michigan Ken Hargreaves, DDS, PhD University of Texas Health Center San Antonio Darnell Kaigler, DDS, PhD University of Michigan David Kohn, PhD University of Michigan Paul Kostenuik, PhD Phylon Pharma Services/ Radius Health, Inc. David Mooney, PhD Wyss Institute at Harvard University Vicki Rosen, PhD Harvard University Charles Sfeir, DDS, PhD University of Pittsburgh Tony Torres University of Pittsburgh William Wagner, PhD University of Pittsburgh

www.mpwrm-doctrc.org

Contacts Program Administration Patrick Cantini

Interdisciplinary Translational Project (ITP) Program Mutsumi Yoshida, PhD

University of Pittsburgh/McGowan Institute 450 Technology Drive, Suite 300 Pittsburgh, Pennsylvania 15219 (412) 624-5209 | cantinip@upmc.edu

University of Michigan – School of Dentistry 1011 North University Avenue, Room 3303 Ann Arbor, Michigan 48109 (734) 764-4622 | yoshidam@umich.edu

Photo courtesy of Emergence Dental/ University of Pittsburgh Histology Core