CRSR, Research, Regenerative Rehabilitation Medical Research Program

About

In 2017, CRSR established the Regenerative and Rehabilitative Medical Research Laboratory, based at USUHS, to advance basic and translational research towards new therapies that combine rehabilitation and regenerative medicine. The portfolio of projects within the lab explore applications of neuroregeneration, orthopaedic tissue repair, vascular regeneration, biomaterials design, three-dimensional (3D) printing, and bioprinting to rehabilitation research.

Our Research

A major focus area for research within the Regenerative Rehabilitation laboratory is on 3D printing and bioprinting of biomaterials and the development of bioinks to fabricate peripheral nerve repair conduits and vascularized tissue grafts for nerve and musculoskeletal repair. During military combat, blast, fragmentary, and ballistic damage to the extremities can result in a spectrum of musculoskeletal trauma that includes injuries to the soft tissues, vessels, nerves, and bone. Currently available surgical treatments for motor, sensory, and mixed peripheral nerve injury include nerve autografts and axonal guidance tubes, but leave substantial room for improvement, especially for larger nerve defects. Without new therapeutics, significant nerve transections resulting from penetrating traumas, such as ammunition or shrapnel, cause significant loss of function for soldiers.

Our studies will demonstrate a potentially transformative first-in-class 3D printed collagen/nerve guide for maintaining nerve and muscle function, along with photobiomodulation therapy (PBMT). Given the higher level of biological and mechanical replication accuracy achievable with 3D bioprinting, we expect better functional recovery in long-gap peripheral repair.

To the best of our knowledge, vascularization has not been incorporated successfully into nerve conduit design. An interlinkage exists between nerve regeneration and vascularization, such that successful axonal growth and long-term survival depends on proper vasculature to allow for oxygen and nutrient supply as well as waste removal, especially in large traumatic injuries. We are developing a 3D printed, perfusable, functional microvascular network that can be directly embedded within 3D printed nerve grafts employed for peripheral nerve regeneration. These studies will lead to clinically meaningful therapies that immensely benefit all individuals, from service members and veterans to civilians, recovering from peripheral nerve or neuromuscular injuries.

Our Collaborators

• Dr. Juanita Anders (USU)
• Dr. Kim Byrnes (USU)
• Dr. Paul George (Stanford)
• Dr. Remi Veneziano (George Mason)
• Dr. Doug Fredericks (Iowa State)

SELECTED Publications/Abstracts

1. Shah Mohammadi M, Buchen JT, Pasquina PF, Niklason LE, Alvarez LM, Jariwala SH*. (2020). Critical considerations for regeneration of vascularized composite tissues. Tissue Engineering Part B: Reviews. Ahead of print. https://doi.org/10.1089/ten.TEB.2020.0223
2. Dixon AR, Jariwala SH*, Bilis Z, Loverde JR, Pasquina PF, Alvarez LM. (2018). Bridging the Gap in Peripheral Nerve Repair with 3D Printed and Bio-printed Conduits. Biomaterials, 186, 44-63. doi.org/10.1016/j.biomaterials.2018.09.010. PMID: 30278345.
3. Steiner R, Phillips E, Buchen J, Pasquina PF, Alvarez LM, Jariwala SH. Evaluation of 3D Printed Collagen Conduits photocrosslinked with Ruthenium for Peripheral Nerve Injury Repair. The AMSUS Hybrid Annual Meeting, February 2022, National Harbor, MD (Poster Presentation).
4. Steiner R, Buchen J, Pasquina PF, Alvarez LM, Jariwala SH. An in vitro 3D printed platform to investigate neuronal interdependency on vascularization for enhancing peripheral nerve repair. The Annual conference of Tissue Engineering and Regenerative Medicine International Society, Inc. (TERMIS), July 2022, Toronto, Canada. Poster presentation..
5. Steiner R, Phillips E, Buchen J, Pasquina PF, Alvarez LM, Jariwala SH. Evaluation of 3D Printed Collagen Conduits photocrosslinked with Ruthenium for Peripheral Nerve Injury Repair. Abstract submitted to the annual meeting of the Military Health System Research Symposium (MHSRS), August 2021, Kissimmee, FL
6. Jariwala SH, Steiner R, Buchen J, Pasquina PF, Alvarez LM. 3D Printed Collagen Conduits for Long-Gap Peripheral Nerve Repair. The Annual meeting of AMSUS, Virtual Meeting, December 2020.
7. Steiner R, Buchen J, Pasquina PF, Alvarez LM, Jariwala SH. An in vitro 3D printed platform to investigate peripheral nerve vascularization. The Annual meeting of AMSUS, Virtual Meeting, December 2020.
8. Jariwala SH, Bilis Z, Shah Mohammadi M, Pasquina PF, Alvarez LM. Assessment of Biomechanical Properties and Biocompatibility of 3D Printed Collagen Nerve Conduits: The Effects of Ruthenium versus Riboflavin Photocrosslinking. The Annual Meeting of Military Health System Research Symposium, Kissimmee, Florida, August 2019.
9. Dixon A, Jariwala SH, Bilis Z, Alvarez LM. Optimization of Photo-crosslinkable Collagen-Enriched Bioink for 3D Printing of Peripheral Nerve Conduits, The Annual meeting of Military Health System Research Symposium, Kissimmee, Florida, August 2018.