Prototype Acceleration (PA)

The Prototype Acceleration Award (PAA) mechanism focuses on advancing novel prototype technologies into the next major stage of development or next major milestone within a 12 month period of performance.  Examples of the next major stage of development/milestone include, but are not limited to:  late animal testing and regulatory filing; manufacturing; next clinical trial; regulatory approval; etc. Projects must eventually result in deliverables that transition medical solutions to government and/or industry partners. The research project award recipients were selected from the Offerors who responded to MTEC’s 17-02-Prototype Acceleration (PA) Request for Project Proposals (17-02-PA).

Pre-clinical assessment of bioprinted human skin for wound healing and skin regeneration (Project Completed)

Project Team: Wake Forest University
Award Amount:  $299,999 (does not include proposed cost share of $150,000)
Project Duration: 12 Months
Project Objectives: The ultimate goal of a skin graft is to regenerate authentic anatomy and physiology of native skin. We have recently demonstrated bioprinting of skin constructs using human cells and matured them in vitro to stratified tri-layered structures containing epidermis, dermis and hypodermis, similar to native human skin. The overall goal of the project is to bioprint full-thickness human skin with hair follicle appendages, microvasculature, immune cells and pigmentation and use it as a skin graft in immunodeficient rats. The bioprinted skin graft will undergo extensive characterization of cell viability in vivo, cellular function, wound healing and skin regeneration. Long-term analyses will assess inflammatory cell infiltration, skin remodeling and potential fibrosis and integration with host tissues. Altogether, the study will constitute preclinical assessment of bioprinted skin graft for treatment of burn injuries and other skin-related injuries.

Accomplishments (Closed-Out): 

The ultimate goal of a skin graft is to regenerate authentic anatomy and physiology of native skin. The team from the Wake Forest School of Medicine completed an optimization process of human skin cell expansion including fibroblasts, pre-adipocytes, keratinocytes and endothelial cells. Using these and other human skin cells, multiple 3×3 cm human skin constructs, containing up to seven different cell types, were successfully fabricated by a custom-made tissue bioprinter (A-C). These bioprinted human skin grafts were used to treat large full thickness wounds in immune-deficient mice. All wounds treated with bioprinted skin closed by day 21, compared with open wounds in control mice (D). The closure of wounds treated with bioprinted skin was primarily due to epithelialization (E) compared with sparse wound coverage, incomplete closure and contraction in control groups. Importantly, 90 days post grafting, the biopronted skin was phenotypically similar to human skin, recapitulated normal collagen remodeling and neovascularization, compared with scar-like tissue in untreated wounds and unorganized skin architecture in wounds treated with hydrogel only (F). Gene expression analysis supported these finding and showed upregulation of expression of Collagen 1 and 3, LOX-2 and MMP 1. Altogether, the results of this study demonstrated maturation and integration of bioprinted human skin into full thickness wounds in mice, along with a significant improvement in wound closure and human skin appearance.

Host-targeted Immune Stimulation by PUL-042 for Prevention of Pneumonia in a Ferret Model of the Damaged Lung

Project Team: Pulmotect, Inc., University of Alabama at Birmingham (Department of Pulmonary, Allergy, and Critical Care)
Award Amount: $300,000
Project Duration: 12 Months
Project Objective: PUL-042 is an innate immune stimulating therapeutic now in early clinical stage drug development. Administered by inhalation, PUL-042 activates defense mechanisms in the epithelial cells that line the lung, resulting in rapid protection from bacterial, viral, and fungal infections. Patients with smoke damaged lungs are especially vulnerable to developing pneumonia caused by infectious microbes, which increases mortality rates and the risks of long-term damage. The funded research study will evaluate the ability of PUL-042 to protect against infectious challenges in a chronic smoke damage model. If successful, PUL-042 could be further developed specifically for patients who have been exposed to smoke from fires and explosions.

Manufacturing of a Negative Pressure Wound Therapy Dressing for Hand Wounds: ReHeal Glove (Project Completed)

Project Team: University of Texas at Arlington, ReHeal LLC
Award Amount: $227,487
Project Duration: 12 Months
Project Objective:  Complex hand wounds can be debilitating and current therapies often fail to restore hands to being adequate for daily living. Vacuum assisted wound closure is an effective method for healing hand injuries but this technique immobilizes the hand which is counterproductive for functional recovery. Our negative pressure wound dressing is an advanced hand wound care system that enables vacuum application while permitting motion during healing to preserve joint range of motion and dexterity. This wound care system is comprised of a flexible and transparent glove-shaped wound dressing which offers a better solution for hand wound care over current technologies. The goal of this project is to develop manufacturing processes and packaging for this wound dressing to enable future clinical trial.

Accomplishments (Closed-out):

The University of Texas at Arlington completed their MTEC Prototype Acceleration Award, where they:

  • Developed a dip molding apparatus
  • Created a mold tooling design and a dip molding process for medical grade silicone
  • Developed an assembly process for attaching the tubing and wrist strap to complete the glove manufacturing process
  • Established basic quality control metrics for the glove
  • Evaluated sterilization and packaging processes
  • Manufactured 100 silicone gloves

After completion of the MTEC award, the team tested the glove on five healthy volunteers at University of Washington – Harborview Medical Center. The glove is now ready to progress into early feasibility pilot trials. MTEC is excited to follow this project through its next set of milestones.

Natural Polymer Microbead and Electrospun Mesh Technologies for the Sustained Release of Regenerative Growth Factors for the Treatment of Burns and Ischemic Wounds (Project Completed)

Project Team: SpherIngenics Inc. and Virginia Commonwealth University
Award Amount: $295,634 (cost share = $46,875)
Project Duration: 12 Months
Project Objective: The objective of this project is to develop and apply a sustained release delivery system for growth factors to promote healing and closure of chronic, ischemic wounds.  Specifically, alginate microbeads will serve as a sustained release delivery system for PLGA microparticles containing angiogenic growth factors VEGF and FGF-2 and will be applied to a challenging clinical model in both wildtype and diabetic rat models.  On the left is an image of the microbeads and microparticles once lyophilized for storage.  The center and right images show the microbeads containing PLGA loaded particles with a fluorescent protein once reconstituted in a physiologically balanced aqueous solution.  The system is lyophilizable allowing for a single step reconstitution in standard physiologic balanced solutions while still maintaining the spherical shape, release kinetics, and protein activity of the system prior to storage.  This greatly enhances shelf life of the product, ease of use and storage considerations.  Finally, the system is injectable through standard syringes and needles, thus alleviating the need for specialized injection, mixing, or curing equipment as is common with current growth factor delivery systems and hydrogels.

Accomplishments (Closed-out):

SpherIngenics, Inc. completed their MTEC Prototype Acceleration Award aimed to develop an alginate microbead technology for the treatment of challenging wounds, such as infected wounds. With MTEC funding, this project developed a system to encapsulate growth factor-loaded microparticles into a sustained release, alginate microbead system. This system was then tested in vitro (bench-top experiments) for the ability to promote angiogenesis (new blood vessel formation). Next, in vivo tests (animal experiments) were performed evaluating this system for wound closure using type I and type II diabetic rats as a model of chronic wounds. Finally, incorporation of silver nanoparticles into the microbead system was tested and shown to be an effective antimicrobial therapeutic to fight against wound infection both in vitro and in vivo. This project is now ready to advance into large animal proof-of-concept studies as the next step toward regulatory application. MTEC is excited to follow this project through its next set of milestones.

Intelligently Engineered Skin for the Treatment of Severe Burns (Project Completed)

Project Team: Upside Biotechnologies Ltd.
Award Amount: $112,500 (cost share = $970,000)
Project Duration: 12 Months
Project Objective: Upside Biotechnology is developing what it believes will be the treatment of choice for sufferers of large burns (greater that one third of the body burnt). Current treatment relies on repeated applications of split skin grafts; an approach which is slow and painful, requires long hospital stays, and often leads to poor cosmetic outcomes. For Upside’s product, an individual suffering from an acute major burn will have a single split skin graft or biopsy taken at the time the burn wound is initially debrided, typically shortly after admission. The skin sample will be sent to a central laboratory where the cells from the skin will be extracted and cultured using proprietary methods. For a typical major burn, it is expected that multiple full-thickness (epidermis and dermis) sheets of skin of 200 x 200 mm will be sent back from the central laboratory, ready to graft onto the patient’s burn after 16 days. The engineered skin is grown in a proprietary chamber on a specially designed, biodegradable, biocompatible mesh that confers excellent handling characteristics.

Accomplishments (Closed-out):

The MTEC project has aided Upside to progress the development of the product to the point where the company has defined the production process, completed the final design of its proprietary growth chamber, undertaken proof of concept work, drafted clinical trial protocol and held its first meeting with the FDA.

Electroceutical Technology Against Bacterial Drug Resistance

Project Team: Indiana University
Award Amount: $200,000 (does not include proposed cost share of $100,000)
Project Duration: 12 Months
Project Objective: Therapeutic flow of Electric Charge (EDT) will be developed as MTEC Technology for prototype acceleration. The following two aims have been proposed: i) Aim 1: To determine the ability of optimized electroceutical EDT dressings to eliminate mixed species, multi-drug resistant infection in an in vitro assay and porcine burn infection model. ii) Aim 2: To test whether wound closure in a pair-matched setting is improved using optimized EDT treatment compared to standard of care (SoC) in biofilm/MDR-infected porcine burn wounds.

Year 1 accomplishments

  • Selected commercial motor neuron source, with in-vitro validation and QC
  • Selected therapeutic delivery formulation consisting of GRAS and cGMP components
  • Selected simple intramuscular injection as the preferred means of therapeutic delivery
  • Selected species for pre-clinical studies
  • Designed all pre-clinical study protocols, including in-vivo end-point measurements