This Small Business Innovation Research (SBIR) Phase I project aims to develop a bioresorbable scaffold material for applications in advanced wound healing, i.e., diabetic ulcers and pressure sores. The specific goal is to develop a highly porous biomaterial that is bifunctional, i.e., used as a dressing material for wounds treated with vacuum therapy (Negative Pressure Wound Therapy-NPWT), and also serve as a scaffold for tissue regeneration. Research shows that patients treated with NPWT have to undergo several painful dressing changes due to the tissue ingrowth that occurs into current dressings. Further, this repeated injury during dressing changes further delays healing. The project will address this important unmet need by developing a resorbable dressing-scaffold material that will allow ingrowth during NPWT, and then degrade at a desired rate to allow normal tissue to be regenerated and organized within the wounds. The technology addresses major clinical unmet needs in advanced wound healing and will produce significant reductions in treatment costs while improving the quality of life for patients who suffer from these debilitating wounds.
The broader impacts of this research are in a variety of applications in tissue regeneration and repair for general, cardiothoracic, and plastic surgery; trauma, sportsmedicine, and fracture healing. This novel scaffold technology will be developed within the framework of large scale foam manufacturing methods using industrial foaming and thermal reticulation techniques. This will also reduce the cost of the biomaterial and substantially impact healthcare spending across a broad range of clinical application areas in the US.
Negative Pressure Wound Therapy (NPWT) using sub-atmospheric pressure has emerged as one of the most promising therapeutic approaches for enabling closure and healing of complex chronic wounds and ulcers. The basic principle of NPWT is the application of constant or intermittent sub-atmospheric pressure to wound surfaces through flexible porous dressing materials packed into the wound, which serve as a medium for exudate removal and also provide biomechanical stimulation. A major challenge with current NPWT systems is the use of temporary non-implantable dressing materials that need to be changed frequently, resulting in traumatic and painful dressing changes which can cause repetitive damage to the newly formed granulation tissue and lead to re-bleeding. This SBIR project addresses the major unmet clinical needs in the treatment of complex wounds using NPWT. The commercial value of this technology is tremendous in that it addresses a multibillion dollar global market in advanced wound care dressings within the framework of NPWT. It has the potential to significantly improve patient quality-of-life, as well as dramatically reduce the cost of health care for patients with complex chronic wounds. More broadly, the technology represents a disruptive change in biomedical scaffolds, and has the potential to lead to innovative, far-reaching, and cost-effective tissue engineering based solutions for a diverse range of therapeutic applications. In the Phase 1 program, Biomerix developed two families of partially and fully degradable bi-functional dressing-scaffold biomaterials with a fast degradation profile of two to three months and an intermediate degradation profile of four to six months. The bi-functional resorbable scaffolds are intended to function as an implantable interface dressing/scaffold during the early therapeutic phase to promote wound closure with minimal disruption to the nascent granulation tissue during dressing changes, and as a three-dimensional tissue scaffold post NPWT to support tissue ingrowth and remodeling. The scaffolds were made by polymerization reaction between isocyanates and polyols in the presence of processing aids. A simultaneous blowing reaction between isocyanate and water produces carbon dioxide (CO2) resulting in porous segmented and cross-linked scaffolds poly (urethane-urea) scaffolds. A thermal reticulation process was used to remove the cell membranes and create an open, porous scaffold with an inter-communicating and inter-connected network of cells and pores. This open porous scaffold is critical to enable fluid transportation during the acute phase of NPWT and tissue ingrowth during the remodeling phase after NPWT application. Two partially resorbable scaffold formulations using biostable aromatic MDI based hard segments with degradable polyester soft segments (PCL/PGA and PCL/PLA copolymer polyols) were successfully developed, and demonstrated properties suitable for satisfying the biomechanical requirements encountered during the acute phases of application of NPWT. Based on in-vitro testing, the program objective of creating partially resorbable scaffolds with fast and intermediate degradation profiles was met. Two fully degradable scaffold formulations using two novel resorbable aromatic diisocyanates with a degradable polyester soft segment (PCL/PGA copolymer polyol) were also successfully developed. Based on in-vitro testing, the program objective of creating a fully degradable scaffold with an intermediate degradation profile was met. The degradation products for all formulations were found to biocompatible. In the proposed Phase 2 program, one degradable dressing-scaffold formulation will be advanced towards commercialization, including formulation optimization, manufacturing scaleup, preclinical studies, and biocompatibility testing.
