(15d) Non-Synthetic Polymer Biomodification Using Gold Nanoparticles | AIChE

(15d) Non-Synthetic Polymer Biomodification Using Gold Nanoparticles

Authors 

Buckley, C. D. - Presenter, The Ohio State University
Vermeersch, K. A. - Presenter, The Ohio State University
Westerfield, J. T. - Presenter, The Ohio State University


Nanoparticles, due to their unique size-dependent properties, provide an opportunity for modification of many biomaterials. Gold nanoparticles are ideal for many of these applications because of their optical characteristics, ability to be synthesized in a variety of sizes, simple conjugation chemistry, and biocompatibility, especially compared to other nanoparticles such as quantum dots. Applications of gold nanoparticle-biomaterial composites include the creation of materials with increased biocompatibility and with the ability to detect the presence of specific biomolecules.

Whereas polymeric biomaterials display excellent mechanical characteristics and compatibility to native tissue, they do not readily support cell adhesion. Unfortunately, modification of these materials can be difficult. For example, agarose and poly (ethylene glycol) (PEG) hydrogel neural tissue mimetics only weakly support cell growth, and cell adhesion molecules must be added to improve the cell-material interface. Methods to chemically modify agarose and PEG hydrogels have been developed, but these methods tend to be difficult and time consuming. A new technique for modification, using gold nanoparticles embedded within a hydrogel matrix, offers a solution to these problems. The particles serve as attachment points for cell adhesion peptides to facilitate bioconjugation. These methods can be applied to many types of hydrogels with different pore sizes simply by changing the nanoparticle size, as opposed to developing novel synthetic chemistry. Several sizes of gold nanoparticles have been synthesized, entrained in agarose hydrogels, and tested to show that the bulk of particles remain in the gel for a substantial length of time. This method does not affect the gel's chemical structure, so changes in mechanical properties should be minimized, allowing the gel to best match the corresponding native tissue. A cell-binding peptide has successfully been conjugated to gold nanoparticles, demonstrating feasibility. The extent of peptide attachment is currently being quantified, and the effect of the peptide on cell growth and adhesion is being studied. Due to its flexibility, this technology is not limited to a single biomaterial, but can be applied to all areas of tissue engineering, providing novel methods of non-synthetic bioconjugation.

In addition to biomodification, these materials offer the opportunity for integrated sensing, due to the well recognized optical properties of gold nanoparticles. Biosensor detection is based on the absorbance shift resulting from surface plasmon resonance (SPR) experienced by aggregated AuNPs. For example, two bound gold nanoparticles experience a SPR-induced absorbance shift as a result of proximity. When the particles are separated, the absorbance returns to its original value. In our proof-of-concept device, particle aggregation is achieved using a cell binding peptide (CGGGRGDSGGGC), whereas cleavage is produced by an enzyme that promotes cell detachment (trypsin), returning particles to their initial unaggregated state. Particles are also modified with tri(ethylene glycol) mono-11-mercaptoundecyl ether, a stabilizing agent that protects the AuNPs from unwanted aggregation. Although our proof-of-concept system examines cell adhesion using the RGD peptide/trypsin protease system, this biosensor could be customized to almost any enzyme-substrate combination. Any substrate with thiol ends (which can be added through cysteine termination) has the ability to bind the AuNPs together, and any substrate specific enzyme can cleave the peptide bond activating the sensor. Thus, analyte sensing can be directly built into the modified hydrogel.

This modification method has numerous advantages. Both the increased biocompatibility and sensing applications of gold nanoparticle-biomaterial composites are improvements over systems based on just hydrogels and polymers or just nanoparticles alone. The combined system provides the hydrogel biomaterials with increased functionality without the requirement of complicated syntheses. In addition, the nanoparticles are provided with a supportive framework. Some of the most promising biosensor models employ aqueous nanoparticles, which are not inherently portable and operate only in the liquid phase. A hydrogel support permits the development of portable devices with potential for gas phase operation. The methods described here are also very flexible as a result of the ability to functionalize the gold nanoparticles with a wide array of biomolecules, providing a composite system with a variety of features.