Projects
We have maintained a 15-year close working relationship with BD (Becton, Dickinson and Company) – BARD, a global medical technology company that seeks to improve the discovery, diagnostics and delivery of healthcare. Our scientific collaborations with BD-BARD involve the design and development of new biomaterial therapies and the improvement of existing therapies for several tissue regeneration applications. In addition, we channel our established pre-clinical models and experimental methodologies towards obtaining regulatory approval for our industry partnerships. At any time, we have 10 actively running projects within BD-BARD, with a with major focus on evaluating the innate and adaptive host response, a critical determinant of the downstream remodelling outcomes.
Our broad pre-clinical work ranges from smaller animal models involving rodents including inbred and genetically modified strains, to larger animal models such as pigs and dogs. The models are used for several indications including hernia repair, volumetric muscle loss, upper and lower GI and surgical site infection. A comprehensive analysis of downstream remodelling outcomes is performed using the facilities in our state-of-the art histology laboratory including histological and immunohistochemical techniques. We also test functional outcomes within these models using mechanical testing equipment to assess strength of hernia repair, electromyography to measure muscle twitch and contraction, isometric torque analysis to measure joint torque and microbiological techniques to evaluate surgical site contamination.
MTEC VML:
“Enhanced Bioscaffold for Volumetric Muscle Loss”
Award Amount: $1,980,707
Principal Investigators (University of Pittsburgh): Dr. Stephen Badylak, DVM, PhD, MD and Dr. J. Peter Rubin, MD, FACS)
Industry Partner: Becton Dickinson
Surgical mesh materials composed of extracellular matrix (ECM) can promote functional tissue remodeling by mechanisms that include stem cell maturation and differentiation and modulation of the host immune response toward a regulatory, pro-healing phenotype. There are two objectives for the present work: 1) to determine if an antibiotic coated version of a biologic scaffold that showed efficacy for promoting muscle regeneration in patients with volumetric muscle loss (VML) in a previous human cohort study could perform equally well, and 2) to develop and test an alternative antibiotic coating that has the added benefit of enhancing the strength of soft tissue repair.
From 2011 to 2015, we conducted a thirteen-patient cohort study in which ECM surgical meshes were used to treat VML. Results showed significant restoration of vascularized, innervated, and functional skeletal muscle with a marked improvement in the quality of life for all patients (ClinicalTrails.gov, identifier NCT01292876). The objective of the present study is to corroborate and extend the findings of the previous study by not only increasing the number of patients treated with this acellular approach, but also utilizing an FDA-approved ECM-based surgical mesh coated with a bioresorbable L-Tyrosine succinate polymer which serves as a carrier for the antibacterial agents Rifampin and Minocycline (XENMATRIX™ AB). The proposed study will assess structure and function in patients undergoing musculotendinous tissue unit repair and reinforcement with XENMATRIX™ AB.
In parallel animal studies, we will evaluate the effect of an enhanced version of XENMATRIX™ AB, coated with doxycycline and Rifampin, upon the healing response and functional outcome in established preclinical animal models of VML. The enhanced version involves a substitution of doxycycline for minocycline. Preliminary studies in our laboratory have shown that XENMATRIX™ with a doxycycline surface coating significantly increased the mesh-fascial interface tensile strength compared to an uncoated XenMatrix™ control in a rat model of incisional hernia repair.
MTEC BIOMFG:
“Large scale manufacturing of extracellular matrix (ECM) hydrogels for regenerative medicine applications”
Funding: $2,208,987
Prime Awardee: University of Pittsburgh (PI: Dr. Stephen Badylak, DVM, PhD, MD)
Subcontractor: ECM Therapeutics, Inc.
A major limitation to widespread clinical translation of extracellular matrix (ECM) hydrogels is the lack of large-scale manufacturing techniques. ECM hydrogel products used for preclinical and clinical studies are fabricated using laboratory‐based processes. Without the development of scalable commercial manufacturing processes, these ECM hydrogel products will fail to meet their true potential in regenerative medicine-based clinical applications.
The objective of the present study is to develop scalable, production ready commercial ECM hydrogel prototypes for use in regenerative medicine clinical applications. This study will advance ECM hydrogel production from laboratory protocols to cGMP-compatible manufacturing processes that will overcome current challenges in ECM hydrogel production and enable clinical translation of this next generation regenerative medicine-based therapy.
DARPA:
Phase 1 Funding: $10,928,518
Prime Awardee: University of Pittsburgh (PI: Dr. Stephen Badylak, DVM, PhD, MD)
Subcontractors: Carnegie Mellon University, Rice University, Northwestern University, University of Vermont, Morgridge Institute for Research, Uniformed Services University of the Health Sciences (USUHS, SC2i)
The REPAIR (Regenerative Electronic Platform through Advanced Intelligent Regulation) project will develop a therapeutic patch with the ability to monitor and regulate key elements of the soft tissue wound healing process to promote functional tissue replacement rather than default scar tissue formation. Key elements of the patch include sensing and actuating bioelectrodes supported by an extracellular matrix (ECM)-based hydrogel. Control of the wound microenvironment is managed by artificial intelligence (AI)-driven algorithms focused upon immunomodulation and innervation at the wound site. The test system for this project is an in vivo model of volumetric muscle loss, a common and debilitating traumatic combat injury. The research team is highly interdisciplinary and comprised of more than 15 separate investigators at seven different academic and military institutions.
The project is split into three main Technical Areas (TAs). TA1 is using bioengineering approaches to develop light-triggered soluble molecules expression, 3D-printed ECM, and unique materials for electrical actuators. TA2 is focused on developing electrical and optical sensors to assess the wound state via measurements of biochemical and biophysical markers of the immune response and the innervation state. TA3 is using mechanistic, agent-based computational models of wound healing, calibrated with spatial data from canine and human combat wounds, to define optimal control policies for the REPAIR patch.
