Current Research

Arborizing Fiberoptic Microneedle Device for Photo-thermo-chemotherapy of Malignant Glioma
The goal of this project is to develop a superior convective-enhanced delivery (CED) treatment for malignant gliomas (MGs), in which a chemotherapeutic drug (carboplatin) is broadly and uniformly delivered with a novel medical device to primary tumors and infiltrative cells (extending >2 cm).

Bio-Mechano-Optic Stimulation and Sensing (BMOSS)
BMOSS is a technology currently under development in the Medical Device Lab. We previously demonstrated the use of mechanical deformation for reducing tissue light scattering and increasing optical penetration depth. 

Bone Scaffolds for Heat Shock Protein Induced Regeneration and Healing
The ultimate goal of this project is to develop a superior bone scaffold through stress conditioning and HSP delivery with the capability to enhance wound healing and bone regeneration in vivo.

Development and Manufacturing of Fiberoptic Microneedle Devices for Cosmetic and Cancer Treatments
Our goals are to: 1) manufacture prototype parallel arrays of FMDs for laser fat removal, and, 2) demonstrate the superior capabilities of FMDs vs. conventional laser lipolysis methods. 

Optical Molecular Tomography for Regenerative Medicine
The overall goal of this project is to develop a first-of-its-kind multi-probe, multi-modal optical molecular tomography (OMT) system for regenerative medicine and to demonstrate its utility in visualizing the real-time development of bioengineered blood vessels, both in bioreactors and after implantation into living animals. 

PAST RESEARCH

Arborizing Fiberoptic Microneedle Device for Photo-thermo-chemotherapy of Malignant Glioma

Sponsor: Coulter Foundation
Performance Period: 9/1/11-8/31/13
PI: Chris Rylander, co-PIs: John Robertson and John Rossmeisl

The goal of this project is to develop a superior convective-enhanced delivery (CED) treatment for malignant gliomas (MGs), in which a chemotherapeutic drug (carboplatin) is broadly and uniformly delivered with a novel medical device to primary tumors and infiltrative cells (extending >2 cm). To accomplish this goal, a fiberoptic microneedle device (FMD) will be developed and utilized as outlined in the Specific Aims:

Aim 1: Design and evaluate FMD prototypes for controlled microneedle arborization and broad distribution of drugs using explanted porcine and canine brain tissue.

Aim 2: Design and evaluate FMD prototypes for photo-thermo-chemotherapeutic (PTC) drug perfusion touniformly saturate selected regions of explanted brain tissue.

Aim 3: Test FMD with caboplatin+Gd-DTPA in canine patients with spontaneous MGs and evaluate treatment with MR imaging.

Photo-thermo-chemotherapeutic treatment of explanted brain tissue with a blue tracer dye.Section through brain region perfused by FMD.

Left: photo-thermo-chemotherapeutic treatment of explanted brain tissue with a blue tracer dye. Right: section through brain region perfused by FMD.

Bio-Mechano-Optic Stimulation and Sensing (BMOSS)

MOSS is a technology currently under development in the Medical Device Lab. We previously demonstrated the use of mechanical deformation for reducing tissue light scattering and increasing optical penetration depth. Such tissue optical responses are inextricably linked to the mechanical stress/strain state of the tissue, particularly the tissue microstructural response to deformation. BMOSS may be able to take advantage of this coupled relationship to in order to diagnose disease states or study mechanobiological behavior.


Trans-illuminated USAF 1951 resolution target viewed through indented 
ex vivo porcine skin. The intensity profile can be used to evaluate image resolution and contrast.


Dynamic responses of (a) Tissue thickness, (b) Compressive load, and (c) Light transmission in indented 
ex vivo porcine skin samples.

Bone Scaffolds for Heat Shock Protein Induced Regeneration and Healing

NSF: CBET: GARDE: 1067654
9/01/2011-8/31/2014

PI: M. Nichole Rylander, co-PIs: Ge Wang, Joseph Freeman, Chris Rylander, and M. Renee Prater

The ultimate goal of this project is to develop a superior bone scaffold through stress conditioning and HSP delivery with the capability to enhance wound healing and bone regeneration in vivo. The transformative nature of the proposed bone scaffold lies in its novel fabrication methods comprised of co-electrospinning polymers coupled with integrated HSP releasing microspheres, conditioning with thermal+tensile stress, and encapsulation of microspheres for HSP release from the scaffold to the surrounding tissue. To accomplish the overall goal, we will complete the following objectives:

1) Construct a novel microbioreactor system to apply combinatorial (thermal+tensile) stress and create a scaffold capable of exogenous HSP delivery and wound healing.

2) Apply combinatorial thermal and tensile stress preconditioning protocols alone and with exogenous HSP delivery to bone scaffolds using a novel microbioreactor system and determine ideal conditions for enhancing bone formation.

3) Evaluate effectiveness of bone scaffolds preconditioned with thermal+tensile stress and HSP delivery to heal bone defects in a rat craniofacial defect model.

Clinical perspective for HSP based scaffolds. Scaffolds containing stem cells will be preconditioned with thermal, mechanical, and biochemical cues (strategy 1). HSP will also be delivered throughout the scaffold using microspheres (carriers) (strategy 2). Scaffold will be implanted in diseased or fractured bone and further regeneration will be promoted by HSP release from the scaffold into the tissue.

Clinical perspective for HSP based scaffolds. Scaffolds containing stem cells will be preconditioned with thermal, mechanical, and biochemical cues (strategy 1). HSP will also be delivered throughout the scaffold using microspheres (carriers) (strategy 2). Scaffold will be implanted in diseased or fractured bone and further regeneration will be promoted by HSP release from the scaffold into the tissue.

Development and Manufacturing of Fiberoptic Microneedle Devices for Cosmetic and Cancer Treatments

Sponsor: Center for Innovative Technology; Commonwealth Research Commercialization Fund
Performance Period: 1/6/2014-1/5/2015,
PI: Chris Rylander, co-PI: John Robertson, Post-doc: Katelyn Colacino

Our goals are to: 1) manufacture prototype parallel arrays of FMDs for laser fat removal, and, 2) demonstrate the superior capabilities of FMDs vs. conventional laser lipolysis methods. To achieve these goals, we will carry out the following specific aims:

Specific Aim 1: Design and manufacture prototype FMDs for demonstration of laser fat removal.

Specific Aim 2: Evaluate performance of FMD prototypes in excised pig skin.

Specific Aim 3: Evaluate FMD fat removal vs. conventional laser fat removal through a comparative study with in vivo pig models.

Fiberoptic Microneedle Device (FMD) schematic illustration of (top) Alternative design #1 using compression between two rigid plates, and (bottom) Alternative design #2 utilizing layered elastomeric ferrule.

Optical Molecular Tomography for Regenerative Medicine

Sponsor: NIH: NHLBI: R01 HL098912
Performance Period: 3/1/10-11/30/13
PI: Ge Wang, co-PIs: Chris Rylander, M. Nichole Rylander, and Yong Xu

The overall goal of this project is to develop a first-of-its-kind multi-probe, multi-modal optical molecular tomography (OMT) system for regenerative medicine and to demonstrate its utility in visualizing the real-time development of bioengineered blood vessels, both in bioreactors and after implantation into living animals. We will achieve the following aims:

Aim 1 – System Prototyping: Develop prototypes for hybrid optical molecular tomography to monitor bioengineered blood vessel constructs in bioreactors (in vitro prototype) and after implantation into sheep (in vivo prototype). We will employ fluorescent probes to label a cylindrical electrospun matrix scaffold and two cell types (vascular endothelial and smooth muscle cells). Optical fibers embedded in the scaffold will facilitate optical coherence tomography (OCT) and optical molecular tomography (OMT). The primary novelty of this multi-modal system lies in the enabling capabilities for multi-probe high-resolution analyses.

Aim 2 – Algorithm Development: Develop processing and reconstruction methods for the proposed optical molecular tomography system. Processing will be needed to minimize any excitation, measurement and reconstruction artifacts/noise. We will perform multi-spectral fluorescence tomography reconstructions based on our new phase-approximation model for photon transport. We will conduct systematic comparison in numerical simulation and tissue phantom experiments to optimize the imaging performance towards the design goals of 100μm 3D resolution in vitro and 500μm 3D resolution in vivo.

Aim 3 – In vitro Studies: Apply the imaging system to assess development of the bioengineered vessels in a pulsatile bioreactor for up to 30 days. We will investigate the endothelial coverage of the scaffold’s luminal surface, migration of smooth muscle cells in the scaffold’s porous outer compartment, and population dynamics of the two cell types. Fluorescent reporters will be utilized to monitor cell-type-specific gene expression in real-time, and to verify physiological responses of cells in the engineered vessel. We will validate optical molecular tomography results by comparison with conventional assays, including histology and measurements of specific mRNA and proteins.

Aim 4 – In vivo Studies: Apply the imaging system to assess the further development of bioengineered blood vessel constructs after anastomosis into the carotid arteries of sheep (up to 4 months). Features of interest to be analyzed are similar to those in vitro, and include scaffold remodeling, and the survival, continued growth and migration, and tissue-appropriate gene expression of cells initially seeded in the vessels. We will validate the OMT results by comparison with traditional histological, molecular, and physiological analyses.