Chronic diabetic foot ulcers are a significant worldwide healthcare burden, reaching a cost of $11 billion in the US alone during 2014. These wounds are notoriously difficult to manage because of slow healing, weak tissue after healing, and high infection rates. Low-cost bandaging and wound dressings are used to treat diabetic wounds in the early stages, but have poor efficacy and often allow progression to the chronic phase, where expensive bioengineered skin substitutes are used. These bioengineered treatments have not shown sufficient efficacy to warrant reimbursement early at their high cost, and thus see low practical efficacy in wound care clinics today. In 2014 there were 100,000+ amputations performed due to diabetic foot ulcers, and the average cost of an outpatient visit was $4500 with ulcer healing rates of only 50%, and recurrence rates above 30%. It is clear that a significant market opportunity exists to create a biomaterial therapy with the efficacy of an advanced skin substitute at the cost of a wound dressing. Low product cost and ease-of-use will drive reimbursement and adoption in the early (acute) phase of wound care, and a regenerative therapy will increase healed tissue mechanical and vascular properties mitigating the chronic wound phase, improving outcomes for patients and reducing costs to payers. Until now, there have been no low cost treatments that when applied can integrate into the wound bed and promote regeneration without sutures or implantation. We at Tempo Therapeutics have developed a fundamentally new synthetic (low cost) poly(ethylene glycol) biomaterial (MAP gel) that is flowable (ease of application) and bonds to the wound bed upon application to produce a material that enables functional tissue regeneration. Our technology is the first of its kind, allowing filling of any shape/size wound bed with a synthetic, low cost product that actually promotes accelerated wound healing and functional tissue regeneration. Upon application within the wound bed, the material is set and bonded to the tissue bed with 30 seconds of white light exposure. This unique approach provides a microporous network of void space in the material where tissue can freely grow into the material before it is degraded. In vivo, the MAP gel enables immediate wound sealing, accelerated healing, and increased regeneration with a single application to the wound taking only minutes. Here we aim to continue the development of the MAP gel for the treatment of slow-healing diabetic wounds. Specifically, we will engineer a slowly degrading material to address slow healing wounds, and harness the modular nature of our material to create degradation profiles that will support large tissue structure formation in vivo (a characteristic unique to the MAP gel and previously unobtainable with current technologies). We will assess both the rate of tissue healing and the amount of tissue regeneration in a diabetic murine wound healing model, as well as the mechanical strength of the reformed tissue after healing compared to current treatments. Completion of our proposed Aims will result lay the groundwork for successful phase II large animal porcine studies of safety and efficacy, ultimately towards a strong FDA portfolio for 510(k) approval.
Public Health Relevance Statement: Public Health Relevance: In the proposed work, we will continue development of the Microporous Annealed Particle (MAP) gel system as a transformative high efficacy, low?cost treatment for diabetic foot ulcers. The MAP gel, the flagship biomaterial technology of Tempo Therapeutics, Inc., has unique characteristics that enable it to completely fill a wound site, allowing strong integration with surrounding tissue, while also enabling fast tissue healing and tissue regeneration. The MAP gel is the first of its kind, enabling tissue healing and regeneration without any further medical intervention. Completion of the proposed Aims will enable Tempo to translate our previous high?efficacy wound treatment in healthy mice to the impaired wound healing in diabetic mice, both in terms of acceleration of healing and increased tissue mechanical properties after wounds are healed. This data will lay the groundwork for phase II studies to support FDA approval via the 510(k) pathway.
Project Terms: Acceleration; Acute; Address; Adoption; Allografting; Amino Acid Substitution; Amputation; Animals; Antibiotic Therapy; Bandage; Beds; Biocompatible Materials; Biomedical Engineering; Blood Vessels; Caring; Characteristics; Chronic; Chronic Phase; chronic wound; Cicatrix; Clinic; cost; Crosslinker; Data; db/db mouse; Debridement; Dermal; Development; diabetic; Diabetic Foot Ulcer; Diabetic mouse; diabetic patient; Diabetic wound; diabetic wound healing; Emollients; Engineering; ethylene glycol; Exposure to; Family suidae; Fibroblasts; Fibrosis; Foundations; Gel; Gelatinase A; Healed; healing; Healthcare; Hematoxylin and Eosin Staining Method; Human; Hydrogels; Impaired wound healing; implantation; improved; improved outcome; in vitro testing; in vivo; Infection; Inflammation; Injectable; Injury; Intervention; Light; Marketing; Matrix Metalloproteinases; Mechanics; Medical; Methods; Modeling; Monitor; Morbidity - disease rate; mortality; mouse model; Mus; Natural regeneration; Nature; Outpatients; particle; Pathway interactions; Patient-Focused Outcomes; Patients; Phase; phase 2 study; Polyethylene Glycols; pre-clinical; Property; public health relevance; Publishing; Recurrence; regenerative therapy; research study; safety study; scaffold; seal; Shapes; Site; Skin Substitutes; Splint Device; Staging; stem; Sterile coverings; Structure; Surgical sutures; System; Technology; Tensile Strength; Therapeutic; Tissue Grafts; tissue regeneration; Tissues; Translating; Treatment Cost; Trichrome stain; Ulcer; Vascularization; Visit; Work; wound; Wound Healing
