The longstanding goals of this laboratory are to understand the fundamental processes involved in creating mechanical barriers to axonal regeneration in situ and ex situ; to develop therapeutic drug delivery systems which promote axonal regeneration; and to develop in vitro cell culture models of central nervous system components to understand which physical and chemical cues guide axon growth. Additionally, we’re developing novel bone cements for vertebroplasty and other applications.
Nerve Regeneration and SCI
We have developed an indentation method to probe microscale mechanical properties of spinal cord tissue in its native state. We use indentation and spectroscopic methods to study fundamental structure-property relationships of the spinal cord and how they change upon injury.
Chondroitin sulfate proteoglycans are upregulated after spinal cord injury, creating a barrier to axonal regeneration. Chondroitinase ABC degrades the inhibitory chondroitin sulfate side chains, permitting axon sprouting. We are working on developing and optimizing several fabrication techniques to create cABC-loaded poly(lactide-co-glycolide) (85:15) microspheres and nanospheres. Currently, research includes characterization of particles created via double emulsion, spontaneous emulsification, and modified single emulsion procedures. We are also characterizing encapsulation and effectiveness of treatment using particles containing glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF).
Cell Culture Models of the CNS
Extracellular matrix (ECM) plays an important role in cell migration, adhesion, and differentiation; thus, it is important to understand the role of ECM proteins in nerve regeneration. We are investigating polyacrylamide (pAA) hydrogels as scaffold material for nerve regeneration since their mechanical properties are easily tunable and their macroporous structure allows for penetration of media to provide a physiological environment. We are studying neurite outgrowth of pheochromocytoma (PC12) cells and primary neurons on pAA substrates demonstrating varying surface chemistry, topography, and moduli.
Bone Cement
Acrylic poly(methyl methacrylate) (PMMA) bone cements have been primarily developed for the augmentation and fixation of total joint arthroplasties in order to provide an interface responsible for stabilization and transferring of mechanical loads between the implant and bone. Even though the mechanical and physical properties of acrylic powder-liquid cements are well understood and described in the literature, there is a vast interest in the development of new cement formulations to overcome the number of drawbacks associated with the application of this material in vivo. Standard two-solution bone cement (STSBC) emerged as an alternative to powder-liquid formulations, having the advantage of being less porous and having higher flexural strength and modulus of elasticity. The simple preparation and mixing procedure associated with a metered delivery on demand make this material attractive for a range of different applications. We have developed novel two-solution cements by the incorporation of cross-linked PMMA microspheres and nanospheres in the powder phase of the cement, as well as by the complete substitution of the linear PMMA by nanospherical brushes (PMMA-g-PMMA) in order to control the initial viscosity of the cement dough at higher polymer-to-monomer ratios. These multi-solution cements are expected to find applications in kyphoplasty and vertebroplasty, which require tailored viscosities and setting characteristics for optimal injection of the material through small cannulas and needles. Cements containing cross-linked PMMA particles present reduced viscosity in comparison to the standard two-solution formulation and adequate mechanical and setting properties for the treatment of vertebral compression fractures.
