Research

  

Research

Our research objective is to better elucidate the mechanisms behind tissue innervation and soft tissue reconstruction. Specifically, we focus on fabricating tissue systems from a variety of biopolymers to generate neurovascular and skeletal muscle tissue mimetics to enhance regeneration and innervation in incidents of traumatic injury, neuropathy, or genetic disorders both in in vitro systems and in vivo.

Some of the projects we are currently pursuing are:

Skeletal Muscle Tissue Regeneration

We focus on developing strategies to understand and augment skeletal muscle regeneration in craniofacial and limb settings. There is a significant need to develop strategies to treat volumetric muscle loss (VML) injuries, which occur from traumatic incidents ranging from car crashes to combat wounds. Our approaches include the development of off-the-shelf biomaterials to augment skeletal muscle repair, and separately we also develop in vitro mimetic tissues to understand the development and repair mechanisms behind skeletal muscle tissue formation.

        Representative Publications

  1. Grasman JM, Do DM, Page RL, Pins GD. Rapid release of growth factors regenerates force output in VML injuries. Biomaterials. Vol 72:49-60, 2015. PMID: 26344363.
  2. Kozan NG, Joshi M, Sicherer ST, Grasman JM. Porous biomaterial scaffolds for skeletal muscle tissue engineering. Frontiers in Bioengineering and Biotechnology. Vol 11:1245897, 2023. PMID: 37854885.
  3. Sicherer ST, Haque N, Parikh Y, Grasman JM. Current methodologies for inducing aligned myofibers in tissue constructs for skeletal muscle tissue regeneration. Advances in Wound Care. Vol 14(2):114-131, 2024. PMID 39126403.
  4. Sicherer ST, Guiliani J, Raju R, Parikh Y, Martin C, Pridmore J, Coombs K, Grasman JM. Effect of ECM proteins on force production of hydrogels seeded with myoblasts. J of Functional Biomaterials. Vol 17(6):299, 2026. PMID: 42346690.
     

Neurovascular Interactions

A major thrust of the lab is to develop 3D tissue models to understand the mechanisms of tissue innervation and neural network formation. We have developed tissue mimetics to study neurovascular interactions and neural network formation as a result of the interplay between the signaling cascades of vascular and neural networks. The model has identified several growth factors essential for the cross-talk between vascular and neural tissues. Interestingly, we are also identifying differences in neurovascular crosstalk based on the age and location of vascular cells, suggesting a regional specificity in the ability of vasculature to support axonal growth in adult tissues. We have characterized one of the first in vitro models of traumatic neural injury from a laceration injury, and are leveraging this system as well as these neurovascular interactions in the peripheral systems to maximize targeted innervation and reveal mechanisms to improve and/or otherwise accelerate peripheral nerve repair.

        Representative Publications

  1. Grasman JM, Kaplan DL. Human endothelial cells secrete neurotropic factors to direct axonal growth. Scientific Reports. Jun 22;7(1):4092, 2017. PMID: 28642578.
  2. Grasman JM, Ferreira JA, Kaplan DL. Tissue models for neurogenesis and repair in 3D. Advanced Functional Materials. Vol 30(25):e1800598, 2018. PMID: 32440261.
  3. Pfister BJ, Grasman JM, Loverde JR. Exploiting biomechanics to direct the formation of nervous tissue. Curr Opin Biomed Eng. Vol 14:59-66, 2020. DOI: 10.1016/j.cobme.2020.05.009.
     

Models and Scaffolds for Neuroengineering

In addition to studying neurovascular interactions, we are employing our hollow channel collagen hydrogel 3D model system to understand how innervation occurs and what signaling events are necessary to stimulate neural growth. We seek to understand the relationship between insoluble and soluble cues to drive axonal growth, as well as to understand the contribution of Schwann cells to enhance peripheral nerve repair. Recently, we have also begun to uncover novel contributions of calcium transience within the neuron that can potentially describe the function of calcium flux on axon growth and recovery after injury. The current system establishes a strong foundation upon which we can build additional complexity in tissue features to study the impact of pharmacologic supplementation or disease conditions for neuronal tissues.

        Representative Publications

  1. Tusnim J, Kutuzov P, Grasman JM. In vitro models for peripheral nerve regeneration. Advanced Healthcare Materials. Vol 13(30):2401605, 2024. PMID: 39324286.
  2. Tusnim J, Budharaju K, Grasman JM. Fabrication of ECM protein coated hollow collagen channels to study peripheral nerve regeneration. Scientific Reports. Vol 14:16096, 2024. PMID: 38997331.
  3. Tusnim J, Pfister BJ, Grasman JM. Dual Role of Ibuprofen and Indomethacin in Promoting Peripheral Nerve Regeneration In Vitro. Tissue Engineering Part A. Vol 31(13-14): 1026-1037, 2025. PMID: 39446790.
  4. Tusnim J, Patel S, Chelala K, O’Connor JP, Pfister BJ, Firestein BL, Grasman JM. Select NSAIDs enhance peripheral nerve growth and calcium signaling through PPARγ activation. Molecular and Cellular Neuroscience. Vol 136:104067, 2026. PMID: 41407133.
     

Biomaterial Customization

Biomaterial synthesis and characterization is critical for successful tissue engineered strategies. We focus on biopolymer (e.g. fibrin, collagen, and silk fibroin) scaffolds and work to tailor the structural, mechanical, and biochemical properties of these materials to enhance therapeutic outcomes. Current foci are in the fields of vascular, neural, and muscle tissue engineering.

        Representative Publications

  1. Grasman JM, Page RL, Dominko T, Pins GD. Crosslinking strategies facilitate tunable structural properties of fibrin microthreads. Acta Biomaterialia. Vol 8(11):4020-30, 2012. PMID: 22824528.
  2. Grasman JM, Williams M, Razis C, Bonzanni M, Golding A, Cairns DM, Levin M, Kaplan DL. Hyperosmolar potassium inhibits myofibroblast conversion and reduces scar tissue formation. ACS Biomaterials Science & Engineering. Vol 5(10):5327-5336, 2019.
  3. Kozan NG, Caswell S, Patel M, Grasman JM. Aligned collagen sponges with tunable pore size for skeletal muscle tissue regeneration. J of Functional Biomaterials. Vol 14(11):533, 2023. PMID 37998102.
  4. Kozan NG, Caswell S, Bolla S, Grasman JM. Aligned Collagen Sponges Loaded with Heparin, IGFBP-5, and IGF-1 Enhance Skeletal Muscle Tissue Regeneration. Journal of Biomedical Materials Research: Part B. Vol 113(8):e35619, 2025. PMID: 40693798.