Regenerative Medicine

In partnership with the US Army Medical Research & Materiel Command (USAMRMC), the Medical Technology Enterprise Consortium (MTEC) is pleased to announce the selectees in the initial round of research project awards issued under its February 29, 2016 Regenerative Medicine Request for Project Proposals. The projects listed at the bottom of this page were selected by the USAMRMC to receive funding as indicated.

The project teams funded through these awards will focus their activities on support areas of regenerative medicine manufacturing and prototyping that require development and harmonization into reproducible, consistent procedures which could stand the test of FDA approval. This emerging area of medical technology and innovation suffers from the lack of standard manufacturing procedures that support a combination product line. Outcomes from the activities conducted under these awards are anticipated to result in well-defined and sufficiently advanced prototypes and manufacturing procedures that may be included in regulatory applications for regenerative medicine products seeking FDA approval.

The research project award recipients were selected from the Offerors who responded to MTEC’s Regenerative Medicine Request for Project Proposals (16-01-REGEN). This solicitation invited proposals in five categories identified by USAMRMC as potential areas of improvement within the regenerative medicine domain.

These areas included:

  • Development of universal, defined culture media for regenerative medicine;
  • Bioreactors to enable efficient and cost-effective cell and tissue expansion for regenerative medicine products;
  • Cell, tissue and product preservation for regenerative and personalized medicine;
  • Large scale manufacturing and quality control of regenerative medicine – based products; and
  • Dynamic and innovative quality control for regenerative medicine manufacturing.

Commercial Scale Up of Bone Marrow-Derived Mesenchymal Stem Cells for Regenerative Medicine

Project Team: BioBridge Global; Rooster Bio, Inc.; StemBioSys; US Army Institute for Surgical Research
Award Amount: $8,079,619
Project Duration: 36 Months
Project Objective: The technology area being investigated is the development of large scale manufacturing and quality control of Regenerative Medicine – based products. The specific goal of this project is to make adult human mesenchymal stem cells manufactured without the use of animal products (i.e. “xeno-free” stem cells) widely available. This will be accomplished by leveraging the partners’ complementary technologies and processes, and adapting, optimizing and validating them for use in xeno-free microcarrier-based bioreactors of increasing capacity (500 mL → 3-5 Liters → 40-80 Liters).  These efforts will yield manufacturing technologies capable of producing commercial-scale, Current Good Manufacturing Practices (cGMP)-compliant stem cells. These cells will benefit both military and civilian regenerative medicine applications by accelerating clinical translation of cell therapies and tissue engineering technologies.

Year One Accomplishments:

  • Commercialized RoosterReplenish™-MSC-XF, a xeno-free human stem cell growth media booster.
  • Optimized 500mL microcarrier bioreactor culture conditions, achieving 200% of stem cell growth efficiency goal – ahead of schedule (400K cells/mL vs. 200K/mL goal).
  • Developed and validated a unique media additive that significantly increases stem cell potency.
  • Established clinical-grade manufacturing processes for making human platelet lysate products from 3 different sources of human platelets.
  • Developed prototype safety and potency assays – to potentiate future clinical use of stem cells.
  • Successfully initiated scale-up of the bioreactor process to 3L – ahead of schedule.
  • Optimization of cell growth and cell harvesting processes ongoing.

Year Two Accomplishments:

  • Developed a 500mL fed-batch bioreactor process (3D) for human stem cells that maintains the functional attributes of planar (2D) grown cells.
  • Scaled up and optimized a 3-5L fed-batch microcarrier bioreactor system that achieved stem cell growth of 430,000 cells/mL, which is over 200% of the stem cell growth efficiency goal of 200,000 cells/mL.
  • Developed a process for closed system harvesting of stem cells from a 3-5L fed-batch microcarrier bioreactor system with high cell recovery, efficient removal of microcarriers, and high post-filtration viability.
  • Completed tech transfer of the 3-5L fed-batch microcarrier bioreactor system from the development lab to a bio-manufacturing lab and demonstrated equivalency of cells expanded between the labs.
  • Completed Phase I and II animal trauma studies with cells generated using the 3-5L fed-batch microcarrier bioreactor system.
  • Successfully scaled-up the 3-5L fed batch microcarrier bioreactor system to a 40-80L bioreactor system.

Manufacture of a Settable Nanocrystalline Hydroxyapatite/Polymer Composite Bone Graft

Project Team: Vanderbilt University; Medtronic
Award Amount: $1,095,160 (does not include proposed cost share of $689,010)
Project Duration: 36 Months
Project Objective: The technology area being investigated is the development of an injectable, settable bone void filler. Proposed activities will support development of a Current Good Manufacturing Practices manufacturing process, validation of stability-indicating analytical methods, and defining animal studies for upcoming regulatory submission to the U.S. Food and Drug Administration (FDA).

Year One Accomplishments:

  • Developed commercial-scale manufacturing processes for raw materials
  • Manufactured kilogram quantities of raw materials
  • Identified preliminary packaging configurations for future testing
  • Demonstrated graft remodeling and new bone formation in a preclinical model of bone regeneration

Year Two Accomplishments:

  • Identified preliminary packaging systems for the bone void filler
  • Scaled-up manufacturing processes for the raw materials
  • Demonstrated that the bone void filler promoted new bone formation in a regulatory preclinical model

Development of Universal Media for the Support and Expansion of Human Cells for Regenerative Medicine Manufacturing

Project Team: RegenMed Development Organization
Award Amount: $5,000,000 (does not include proposed cost share of $5,200,000)
Project Duration: 60 Months
Project Objective: The overall objective of this project is to develop a well-defined xeno-free basal medium that supports the growth and viability of human cells derived from each of the three germ layers, and that can be used in conjunction with three specific supplements, each of which has been optimized to support the expansion of cells derived from one of the three germ layers. These germ layer-specific formulations will then be augmented with additional factors tailored to support the growth and function of several specific human cell types commonly employed in regenerative medicine. Since all formulations will be derived from the same “universal” basal medium, review by domestic and regulatory agencies will be greatly simplified and manufacturing costs will be substantially lowered.

Years One and Two Accomplishments:

  • Developed extensive growth curves, morphology panels, and cell viability characterization data for mesoderm-derived cell types grown in commercial media (containing animal serum) and our chemically-defined, xeno free medium using industry cost shared instrumentation (IncuCyte S3 Live Cell Imager and NC 200 Cell Counter).
  • Performed cost of goods analysis with industry collaborators on our media formulation to identify key cost drivers and potential alternatives/replacements.
  • Collaborated with biomedical industry leaders to develop immunophenotypic panels for characterizing cells using flow cytometry and immunocytochemistry techniques.
  • Successfully worked with an industry collaborator to manufacture 20L of our final chemically-defined, xeno-free medium developed for mesoderm-derived cell types.
  • Established documentation for over thirteen different research related processes to develop standard procedures and validation strategies.

Year Three Accomplishments

  • Formulated two Universal media for the support of ectoderm and endoderm derived cell types based upon the previously developed mesoderm medium.
  • Developed supplement packs for the support of challenging cell types, including cells of the nervous system such as Schwann cells, astrocytes, and glial cells.
  • Performed an independent secondary site validation of universal media performance for mesoderm and ectoderm derived cell types.
  • Demonstrated the clinical scale expansion of bone marrow mesenchymal stem in  ReMDO universal medium.
  • Created a library of cell performance data sheets, including standardized procedures and validation metrics, for expanding specific human cell types in ReMDO media.
  • Collaborated with industry partners to develop tissue culture substrates for facilitating epithelial cell growth.
  • Successfully worked with Industry cost share partners to develop supplement packs comprised of FDA approved reagents.
  • Collaborated with industry cost share partners to develop a metabolic panel to qualitatively define cell proliferation.

Development of a Universal Bioink with Tunable Mechanical Properties for Regenerative Medicine Additive Manufacturing of Clinical Products

Project Team: RegenMed Development Organization
Award Amount: $5,000,000 (does not include proposed cost share of $5,200,000)
Project Duration: 60 Months
Project Objective: The overall objective of this project is to formulate a base bioink with a modular cocktail of cross-linkers that can be used to tune the mechanical properties of the hydrogel, both for bioprinting, and for adjusting the final stiffness of the bioprinted construct to match the stiffness of native tissues, ensuring optimal cell survival and tissue construct function. A series of bioprinting experiments will be conducted using several representative human cell types, with various bioink formulations and across a range of printing resolutions, to confirm that the greatest bioprinting speed is attainable while maintaining construct ultrastructure, cell viability, and function. A library of formulations using the standardized components will then be generated to provide reference points for fine tuning bioinks for additional applications. The development of this almost infinitely tunable bioink formulation will make it possible to achieve cost efficient manufacturing of a wide range of bioprinted regenerative medicine products.

Years One and Two Accomplishments:

  • Developed extrusion bioink comprised of native extracellular matrix components found naturally in human tissue, engineered to support bioprinting applications.
  • Customized modular bioink formulations to support a wide variety of cell types, ranging from common cell lines, primary cells from various tissue types, stem cells, and patient-specific cell populations based on industry collaborator’s needs, preferences, and commercial market.
  • Developed a modular bioink that is compatible with all extrusion bioprinting platforms, and has been tested across the most common bioprinter devices in the industry.
  • Engineered a technology platform that supports biofabrication of 3D tissue constructs, as well as increased throughput of organoid generation for drug screening and personalized medicine applications.Year Three Accomplishments
  • Developed functionalized bioink comprised of native extracellular matrix components found naturally in human tissue, which can be modified to be compatible with both extrusion and inkjet printing.
  • Developed standardized techniques to measure printability of inkjet bioink formulations, allowing us to predict its compatibility with the inkjet printing modality and quantify its printing resolution.
  • Created a library of customizable modular biochemical formulations to support a variety cell types, ranging from common cell lines, primary cells from various tissue types, stem cells, and patient-specific cell populations.
  • Developed SOPs documenting the synthesis process for the functionalized bioink components and creation of tissue specific formulations