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:

Neural Engineering and 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, and we are characterizing traumatic injury models within this system to understand mechanisms behind neural repair and network reformation.

        Representative Publications

  1. Grasman JM, Kaplan DL. Human endothelial cells secrete neurotropic factors to direct axonal growth. Scientific Reports. Jun 22;7(1):4092. doi: 10.1038/s41598-017-04460-8, 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. doi: 10.1002/adfm.201803822, 2018. PMID: 29717798.

Skeletal Muscle Tissue Engineering

The second major thrust of the lab is to develop 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 also to 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. Grasman JM, Zayas MJ, Page RL, Pins GD. Biomimetic scaffolds for regeneration of volumetric muscle loss in skeletal muscle injuries. Acta Biomaterialia. Vol 25:2-15, 2015. PMID: 26219862.
  3. Grasman JM, Page RL, Pins GD. Design of an in vitro model of cell recruitment for skeletal muscle regeneration using HGF-loaded fibrin microthreads. Tissue Engineering Part A. Vol 23(15-16):773-783, 2017. PMID: 28351217.
  4. Zhao S, Tseng P, Grasman J, Wang Y, Li W, Yavuz B, Chen Y, Howell L, Rincon J, Omenetto FG, Kaplan DL. Programmable hydrogel ionic circuits for biologically matched electronic interfaces.  Advanced Materials. Vol 30(25):e1800598, 2018.

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, Pumphrey L, Dunphy M, Perez-Rogers J, Pins GD. Static axial stretching enhances the mechanical properties and cellular responses of fibrin microthreads. Acta Biomaterialia. Vol 10(10):4367-76, 2014. PMID: 24954911.
  3. Grasman JM, O'Brien MP, Ackerman K, Gagnon KA, Wong GM, Pins GD. The effect of sterilization methods on the structural and chemical properties of fibrin microthread scaffolds. Macromolecular Biosciences. Vol 16:836-46, 2016. PMID: 26847494.
  4. 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.