Roland Stone

The formation of linear aggregates in magnetic hyperthermia: implications on specific absorption rate and magnetic anisotropy.

The design and application of magnetic nanoparticles for use as magnetic hyperthermia agents has garnered increasing interest over the past several years. When designing these systems, the fundamentals of particle design play a key role in the observed specific absorption rate (SAR). This includes the particles core size, polymer brush length, and colloidal arrangement. While the role of particle core size on the observed SAR has been significantly reported, the role of the polymer brush length has not attracted as much attention. It has recently been reported that for some suspensions linear aggregates form in the presence of an applied external magnetic field, i.e. chains of magnetic particles. The formation of these chains may have the potential for a dramatic impact on the biomedical application of these materials, specifically the efficiency of the particles to transfer magnetic energy to the surrounding cells. In this study we demonstrate the dependence of SAR on magnetite nanoparticle core size and brush length as well as observe the formation of magnetically induced colloidal arrangements. Colloidally stable magnetic nanoparticles were demonstrated to form linear aggregates in an alternating magnetic field. The length and distribution of the aggregates were dependent upon the stabilizing polymer molecular weight. As the molecular weight of the stabilizing layer increased, the magnetic interparticle interactions decreased therefore limiting chain formation. In addition, theoretical calculations demonstrated that interparticle spacing has a significant impact on the magnetic behavior of these materials. This work has several implications for the design of nanoparticle and magnetic hyperthermia systems, while improving understanding of how colloidal arrangement affects SAR.

Investigation of the stability of magnetite nanoparticles functionalized with catechol based ligands in biological media

A novel tri-nitroDOPA terminated polymer based ligand has been developed for the stabilization of magnetite nanoparticles. The synthesis involves a process in which ethylene oxide is polymerized using a trivinyl initiator, modified with carboxylic acid using a free radical addition of mercaptoundecanoic acid, and then functionalized with nitroDOPA using N,N′-dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide (NHS) chemistry. This newly synthesized polymer is then compared to more traditional monofunctional catechol based ligands of similar molecular weights (∼5000 g mol−1), by testing their effectiveness at stabilizing magnetite nanoparticles (∼6.5 nm in diameter) in biological media. Colloidal stability was tested using dynamic light scattering (DLS) and thermal gravimetric analysis (TGA) to observe the change in particle stability when influenced by phosphate buffered saline (PBS). The time dependent stability of these polymer-coated aqueous suspensions of magnetite was then analysed using DLS to observe the change in the hydrodynamic diameter as a function of time in both PBS and fetal bovine serum (FBS). It was observed over the course of this study that magnetite particles stabilized with PEO-tri-nitroDOPA were more stable than their monofunctional counterparts, retaining stability inside PBS for extended periods of time with no sign of significant hydrodynamic size change and only 8.1% polymer loss over 48 hours in PBS. This is a significant improvement compared to the monocoatechol polymer ligands, where losses of polymer coating of 32.2% were recorded along with large increases of hydrodynamic diameter. The tri-nitroDOPA polymer also displayed stability in FBS over 24 hours, as where the monocatechol ligands displayed heavy clustering and sedimentation over the same time period.

Highly stable multi-anchored magnetic nanoparticles for optical imaging within biofilms.

Magnetic nanoparticles are the next tool in medical diagnoses and treatment in many different biomedical applications, including magnetic hyperthermia as alternative treatment for cancer and bacterial infections, as well as the disruption of biofilms. The colloidal stability of the magnetic nanoparticles in a biological environment is crucial for efficient delivery. A surface that can be easily modifiable can also improve the delivery and imaging properties of the magnetic nanoparticle by adding targeting and imaging moieties, providing a platform for additional modification. The strategy presented in this work includes multiple nitroDOPA anchors for robust binding to the surface tied to the same polymer backbone as multiple poly(ethylene oxide) chains for steric stability. This approach provides biocompatibility and enhanced stability in fetal bovine serum (FBS) and phosphate buffer saline (PBS). As a proof of concept, these polymer-particles complexes were then modified with a near infrared dye and utilized in characterizing the integration of magnetic nanoparticles in biofilms. The work presented in this manuscript describes the synthesis and characterization of a nontoxic platform for the labeling of near IR-dyes for bioimaging.

Mechanical characterization of a bifunctional Tetronic hydrogel adhesive for soft tissues

Although a number of tissue adhesives and sealants for surgical use are currently available, attaining a useful balance in high strength, high compliance, and low swelling has proven difficult. Recent studies have demonstrated that a four-arm poly(propylene oxide)-poly(ethylene oxide) block copolymer, Tetronic, can be chemically modified to form a hydrogel tissue adhesive (Cho et al., Acta Biomater 2012;8:2223-2232; Barrett et al., Adv Health Mater 2012;1-11; Balakrishnan, Evaluating mechanical performance of hydrogel-based adhesives for soft tissue applications. Clemson University, All Theses, Paper 1574: Tiger Prints; 2013). Building on the success of these studies, this study explored bifunctionalization of Tetronic with acrylates for chemical crosslinking of the hydrogel and N-hydroxysuccinimide (NHS) for reaction with tissue amines. The adhesive bond strengths of various uni and bifunctional Tetronic blends (T1107 ACR: T1107 ACR/NHS) determined by lap shear testing ranged between 8 and 74 kPa, with the 75:25 (T1107 ACR: T1107 ACR/NHS) blend displaying the highest value. These results indicated that addition of NHS led to improvement of tissue bond strength over acrylation alone. Furthermore, ex vivo pressure tests using the rat bladder demonstrated that the bifunctional Tetronic adhesive exhibited high compliance and maintained pressures under hundreds of filling and emptying cycles. Together, the results of this study provided evidence that the bifunctional Tetronic adhesive with a proper blend ratio may be used to achieve an accurate balance in bulk and tissue bond strengths, as well as the compliance and durability for soft tissue such as the bladder.

Society for biomaterials student award winner in the graduate degree category, 2015 annual meeting and exposition, charlotte, NC, April 15-18, 2015

Although a number of tissue adhesives and sealants for surgical use are currently available, attaining a useful balance in high strength, high compliance, and low swelling has proven difficult. Recent studies have demonstrated that a four-arm poly(propylene oxide)-poly(ethylene oxide) block copolymer, Tetronic, can be chemically modified to form a hydrogel tissue adhesive (Cho et al., Acta Biomater 2012;8:2223-2232; Barrett et al., Adv Health Mater 2012;1-11; Balakrishnan, Evaluating mechanical performance of hydrogel-based adhesives for soft tissue applications. Clemson University, All Theses, Paper 1574: Tiger Prints; 2013). Building on the success of these studies, this study explored bifunctionalization of Tetronic with acrylates for chemical crosslinking of the hydrogel and N-hydroxysuccinimide (NHS) for reaction with tissue amines. The adhesive bond strengths of various uni and bifunctional Tetronic blends (T1107 ACR: T1107 ACR/NHS) determined by lap shear testing ranged between 8 and 74 kPa, with the 75:25 (T1107 ACR: T1107 ACR/NHS) blend displaying the highest value. These results indicated that addition of NHS led to improvement of tissue bond strength over acrylation alone. Furthermore, ex vivo pressure tests using the rat bladder demonstrated that the bifunctional Tetronic adhesive exhibited high compliance and maintained pressures under hundreds of filling and emptying cycles. Together, the results of this study provided evidence that the bifunctional Tetronic adhesive with a proper blend ratio may be used to achieve an accurate balance in bulk and tissue bond strengths, as well as the compliance and durability for soft tissue such as the bladder.

Mechanical characterization of a bifunctional Tetronic hydrogel adhesive for soft tissues: Society for Biomaterials Student Award Winner in the Graduate Degree Category, 2015 Annual Meeting and Exposition, Charlotte, NC, April 15-18, 2015

Although a number of tissue adhesives and sealants for surgical use are currently available, attaining a useful balance in high strength, high compliance, and low swelling has proven difficult. Recent studies have demonstrated that a four-arm poly(propylene oxide)-poly(ethylene oxide) block copolymer, Tetronic, can be chemically modified to form a hydrogel tissue adhesive (Cho et al., Acta Biomater 2012;8:2223-2232; Barrett et al., Adv Health Mater 2012;1-11; Balakrishnan, Evaluating mechanical performance of hydrogel-based adhesives for soft tissue applications. Clemson University, All Theses, Paper 1574: Tiger Prints; 2013). Building on the success of these studies, this study explored bifunctionalization of Tetronic with acrylates for chemical crosslinking of the hydrogel and N-hydroxysuccinimide (NHS) for reaction with tissue amines. The adhesive bond strengths of various uni and bifunctional Tetronic blends (T1107 ACR: T1107 ACR/NHS) determined by lap shear testing ranged between 8 and 74 kPa, with the 75:25 (T1107 ACR: T1107 ACR/NHS) blend displaying the highest value. These results indicated that addition of NHS led to improvement of tissue bond strength over acrylation alone. Furthermore, ex vivo pressure tests using the rat bladder demonstrated that the bifunctional Tetronic adhesive exhibited high compliance and maintained pressures under hundreds of filling and emptying cycles. Together, the results of this study provided evidence that the bifunctional Tetronic adhesive with a proper blend ratio may be used to achieve an accurate balance in bulk and tissue bond strengths, as well as the compliance and durability for soft tissue such as the bladder.