March 8, 2013 Sigma Xi Competition

Hydrogel Composites with Carbon Nanobrushes for Tissue

Engineering

William H. Marks & Carolina I. Ragolta

Additional AuthorsSze C. Yang, George W. Dombi, & Sujata K. Bhatia

Medical Need: Cardiac Regeneration✤ Coronary Artery Disease

is a leading killer of men and women worldwide

✤ Congestive heart failure has 1-year mortality rate of 40%

✤ Image Source: National Heart Lung and Blood Institute

Medical Need: Cardiac Regeneration✤ Myocardial infarction

can lead to death of 109 cardiomyocytes

✤ 1.5 million Americans suffer myocardial infarctions each year

✤ Image Source: Medicine.net

Abstract

✤ Study carbon nanobrushes (CNBs) embedded in hydrogels for scaffolding in tissue engineering

✤ CNBs provide internal structure, conductivity, and are non-toxic

✤ Tested the ability of fibroblasts and myocytes to adhere to the gel and mechanical properties

✤ CNBs alter mechanical properties providing a high degree of customization

✤ Gels show promise for many wound healing applications

Medical Need: Regenerative Medicine

✤ Biomaterials must be biocompatible, non-cytotoxic, non-hemolytic, and non-inflammatory

✤ They must degrade within the physiologic environment

✤ Must be easily prepared, implantable, and scalable✤ Must be clinically relevant

Prior Related Work

✤ Cell encapsulation for 3D tissue growth (Hunt et al., 2010)✤ Collagen matrices for fibrogenesis (Chen et al., 2009)✤ Alginate gels with carbon nanotubes provide mild

inflammatory response (Kawaguchi et al., 2006)✤ “Scar in a Jar” collagen matrix for flexor tendon healing

(Dombi et al., 1994)✤ Cartilage tissue engineering by accurately spinning

hydrogels (Coburn et al., 2011)

Clinically Relevant Cell Lines

Primary Cardiac FibroblastsSource: Dr. Andrew Pelling, UCL

Primary Cardiac MyocytesSource: Dr. Poling Kuo, Harvard

Carbon Nanobrushes

✤ Electrically conducting polymers grafted onto carbon nanotubes

✤ Conductivity of materials is about 0.1 S/cm

✤ 5-20µm in length✤ 13-30nm in diameter✤ Imaged by negatively

staining with phosphotungstate

Pluronic F-127 Poloxamer Hydrogels✤ Reverse phase-change properties: solid at 37 , liquid at ℃

room temperature✤ Triblock copolymer of PEO-PPO✤ Non-ionic and biocompatible

Preparation of Composite Hydrogels with Carbon Nanobrushes✤ 30wt% poloxamer solution✤ Various CNB

concentrations✤ 0vol%✤ 0.1vol%✤ 0.5vol%✤ 1vol%

✤ Solidified at 37 and then ℃seeded with cells and DMEM

Growth of Fibroblasts

Fibroblasts in top layer of poloxamer gel after 48 hours

Migration of Fibroblasts

Fibroblasts in middle layer of poloxamer gel after 48 hours

Fibroblasts in bottom layer of poloxamer gel after 48 hours

Growth of Myocytes

Myocytes in top layer of poloxamer gel after 48 hours

Rheology: Temperature Sweep

Temperature sweep test of gels containing 0vol% and 5vol% CNB

Rheology: Time Sweep

Time sweep test of gels containing 0vol% and 5vol% CNB at 37℃

Rheology: Frequency Sweep

Frequency sweep test of gels containing 0vol% and 5vol% CNB at 37 ℃showing a crossover from predominately elastic to predominately viscous

Discussion

✤ Hydrogels embedded with CNBs support cell growth and migration

✤ CNBs change the properties of the gel on a macro scale by altering the frequency of the sol-gel transition point✤ Gels transition from predominately elastic to

predominately viscous✤ Additional degree of customizability

Ongoing and Future Work

✤ Properties of gels with different wt% of poloxamer✤ Incorporating crosslinkers into hydrogels✤ Injectability✤ Experiments with additional cell lineages

Translational Potential

Tissue PatchesSource: Gore

Skin GraftsSource: Medline

Tissue ScaffoldSource: National

Institute of Standards and Technology

Acknowledgements

✤ Dr. Sujata K. Bhatia, SEAS, Harvard

✤ Dr. Sze C. Yang, University of Rhode Island

✤ Dr. George W. Dombi, University of Rhode Island

✤ Dr. Patrick Campbell, SEAS, Harvard (Disease Biophysics Group)

✤ Harvard School of Engineering and Applied Sciences