Melissa A. Grunlan

Photo-cross-linked PDMSstar-PEG hydrogels: synthesis, characterization, and potential application for tissue engineering scaffolds.

Inorganic-organic hydrogels with tunable chemical and physical properties were prepared from methacrylated star polydimethylsiloxane (PDMS(star)-MA) and diacrylated poly(ethylene glycol) (PEG-DA) for use as tissue engineering scaffolds. A total of 18 compositionally unique hydrogels were prepared by photo-cross-linking, varying weight ratios of PEG-DA and PDMS(star)-MA of different molecular weights (M(n)): PEG-DA (M(n) = 3.4k and 6k g/mol) and PDMS(star)-MA (M(n) = 1.8k, 5k, and 7k g/mol). Introduction of PDMS(star)-MA caused formation of discrete PDMS-enriched microparticles dispersed within the PEG matrix. The swelling ratio, mechanical properties in tension and compression, nonspecific protein adhesion, controlled introduction of bioactivity, and cytotoxicity of hydrogels were studied. This library of inorganic-organic hydrogels with tunable properties provides a useful platform to study the effect of scaffold properties on cell behavior.

Influence of hydrogel mechanical properties and mesh size on vocal fold fibroblast extracellular matrix production and phenotype.

Current clinical management of vocal fold (VF) scarring produces inconsistent and often suboptimal results. Researchers are investigating a number of alternative treatments for VF lamina propria (LP) scarring, including designer implant materials for functional LP regeneration. In the present study, we investigate the effects of the initial scaffold elastic modulus and mesh size on encapsulated VF fibroblast (VFF) extracellular matrix (ECM) production toward rational scaffold design. Poly(ethylene glycol) diacrylate (PEGDA) hydrogels were selected for this study since their material properties, including mechanical properties, mesh size, degradation rate and bioactivity, can be tightly controlled and systematically modified. Porcine VFF were encapsulated in four PEGDA hydrogels with degradation half lives of approximately 25 days, but with initial elastic compressive moduli and mesh sizes ranging from approximately 30 to 100kPa and from approximately 9 to 27nm, respectively. After 30 days of static culture, VFF ECM production and phenotype in each formulation was assessed biochemically and histologically. Sulfated glycosaminoglycan synthesis increased in similar degree with both increasing initial modulus and decreasing initial mesh size. In contrast, elastin production decreased with increasing initial modulus but increased with decreasing initial mesh size. Both collagen deposition and the induction of a myofibroblastic phenotype depended strongly on initial mesh size but appeared largely unaffected by variations in initial modulus. The present results indicate that scaffold mesh size warrants further investigation as a critical regulator of VFF ECM synthesis. Furthermore, this study validates a systematic and controlled approach for analyzing VFF response to scaffold properties, which should aid in rational scaffold selection/design.

The influence of poly(ethylene oxide) grafting via siloxane tethers on protein adsorption

Amphiphilic PEO-silanes (a-c) having siloxane tethers of varying lengths with the general formula alpha-(EtO)3Si-(CH2)2-oligodimethylsiloxane(n)-block-poly(ethylene oxide)8-OCH3 [n=0 (a), n=4 (b), and n=13 (c)] were grafted onto silicon wafers and resistance to adsorption of plasma proteins was measured. Distancing the PEO segment from the hydrolyzable triethoxysilane [(EtO)3Si] grafting group by a oligodimethylsiloxane tether represents a new method of grafting PEO chains to surfaces. Properties of surfaces grafted with a-c were compared to surfaces grafted with a traditional PEO-silane containing a propyl spacer [(EtO)3Si-(CH2)3-poly(ethylene oxide)8-OCH3, PEO control]. As the siloxane tether length increased, chain density of PEO-silanes grafted onto oxidized silicon wafers decreased and hydrophobicity of the PEO-silane increased which led to a decrease in surface hydrophilicity. Despite decreased surface hydrophilicity, resistance to the adsorption of bovine serum albumin (BSA) increased in the order: PEO control

Design of a self-cleaning thermoresponsive nanocomposite hydrogel membrane for implantable biosensors.

Following implantation of a biosensor, adhesion of proteins and cells and eventual fibrous encapsulation will limit analyte diffusion and impair sensor performance. A thermoresponsive nanocomposite hydrogel was developed as a self-cleaning biosensor membrane to minimize the effect of the host response and its utility for an optical glucose sensor, demonstrated here. It was previously reported that thermoresponsive nanocomposite hydrogels prepared from photopolymerization of an aqueous solution of N-isopropylacrylamide (NIPAAm) and polysiloxane colloidal nanoparticles released adhered cells with thermal cycling. However, poly(N-isopropylacrylamide) hydrogels exhibit a volume phase transition temperature (VPTT) of approximately 33-34 degrees C, which is below body temperature. Thus, the hydrogel would be in a collapsed state in vivo, which would ultimately limit diffusion of the target analyte (e.g., glucose) to the encapsulated sensor. In this study, the VPTT of the nanocomposite hydrogel was increased by introducing N-vinylpyrrolidone (NVP) as a comonomer, so that the hydrogel was in the swollen state in vivo. This thermoresponsive nanocomposite hydrogel was prepared by the photopolymerization of an aqueous solution of NIPAAm, NVP, and polysiloxane colloidal nanoparticles. In addition to a VPTT a few degrees above body temperature, the hydrogel also exhibited good mechanical strength, glucose diffusion, and in vitro cell release upon thermal cycling. Thus, this nanocomposite hydrogel may be useful as a biosensor membrane to minimize biofouling and extend the lifetime and efficiency of implantable glucose sensors and other biosensors.

Biomechanical properties of synthetic and biologic graft materials following long-term implantation in the rabbit abdomen and vagina

OBJECTIVE We sought to evaluate the effects of anatomic location and ovariectomy on biomechanical properties of synthetic and biologic graft materials after long-term implantation. STUDY DESIGN A total of 35 rabbits underwent ovariectomy or sham laparotomy and were implanted with polypropylene (PP) mesh (n = 17) or cross-linked porcine dermis (PS) (n = 18) in the vagina and abdomen. Grafts were harvested 9 months later and underwent mechanical properties testing. RESULTS After implantation, PS was similar in strength (P = .52) but was twice as stiff as PP (P = .04) and had a maximal elongation only half that of PP (P < .001). Degradation of PS was associated with decreased ultimate tensile strength (P = .03) and elastic modulus (P = .046). Vaginal PP grafts shrunk more (P < .001) and were less stiff than abdominal PP grafts (P = .049) but were not different in strength (P = .19). Ovariectomy had no effect (P > .05). CONCLUSION Cross-linked PS undergoes long-term degradation resulting in compromised biomechanical properties and thus is likely inferior to lightweight PP meshes for pelvic organ prolapse and incontinence procedures.

Bacteria and diatom resistance of silicones modified with PEO-silane amphiphiles

Silicone coatings with enhanced antifouling behavior towards bacteria, diatoms, and a diatom dominated slime were prepared by incorporating PEO-silane amphiphiles with varied siloxane tether lengths (a–c): α-(EtO)3Si(CH2)2-oligodimethylsiloxanen-block-poly(ethylene oxide)8-OCH3 [n = 0 (a), 4 (b), and 13 (c)]. Three modified silicone coatings (A–C) were prepared by the acid-catalyzed sol–gel cross-linking of a–c, respectively, each with a stoichiometric 2:3 M ratio of α, ω-bis(Si–OH)polydimethylsiloxane (Mn = 3,000 g mol−1). The coatings were exposed to the marine bacterium Bacillus sp.416 and the diatom (microalga) Cylindrotheca closterium, as well as a mixed community of Bacillus sp. and C. closterium. In addition, in situ microfouling was assessed by maintaining the coatings in the Atlantic Ocean. Under all test conditions, biofouling was reduced to the highest extent on coating C which was prepared with the PEO-silane amphiphile having the longest siloxane tether length (c).

Ultra-strong thermoresponsive double network hydrogels†

Thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels are widely studied smart materials, particularly for biomedical applications, but are limited by their mechanical strength. In this study, double network (DN) hydrogels were prepared with an asymmetric crosslink design and inclusion of an electrostatic co-monomer, 2-acrylamido-2-methylpropane sulfonic acid (AMPS). These P(NIPAAm-co-AMPS)/PNIPAAm DN hydrogels were sequentially formed with a tightly crosslinked 1st network comprised of variable levels of AMPS (100 : 0 to 25 : 75 wt% ratio of NIPAAm:AMPS) and a loosely crosslinked 2nd network comprised of PNIPAAm. The impact of AMPS content in the 1st network on the volume phase transition temperature (VPTT), morphology, deswelling-reswelling kinetics and mechanical properties was evaluated. Without substantially altering the VPTT of conventional PNIPAAm hydrogels but with improving thermosensitivity, the DN hydrogel formed with 25 : 75 wt% of NIPAAm:AMPS achieved exceptional strength, high modulus and high %strain at break.

Development of a self-cleaning sensor membrane for implantable biosensors

Fibrous tissue encapsulation may slow the diffusion of the target analyte to an implanted sensor and compromise the optical signal. Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels are thermoresponsive, exhibiting temperature-modulated swelling behavior that could be used to prevent biofouling. Unfortunately, PNIPAAm hydrogels are limited by poor mechanical strength. In this study, a unique thermoresponsive nanocomposite hydrogel was developed to create a mechanically robust self-cleaning sensor membrane for implantable biosensors. This hydrogel was prepared by the photochemical cure of an aqueous solution of NIPAAm and copoly(dimethylsiloxane/methylvinylsiloxane) colloidal nanoparticles ( approximately 219 nm). At temperatures above the volume phase transition temperature (VPTT) of approximately 33-34 degrees C, the hydrogel deswells and becomes hydrophobic, whereas lowering the temperature below the VPTT causes the hydrogel to swell and become hydrophilic. The potential of this material to minimize biofouling via temperature-modulation while maintaining sensor viability was investigated using glucose as a target analyte. PNIPAAm composite hydrogels with and without poration were compared to a pure PNIPAAm hydrogel and a nonthermoresponsive poly(ethylene glycol) (PEG) hydrogel. Poration led to a substantial increase in diffusion. Cycling the temperature of the nanocomposite hydrogels around the VPTT caused significant detachment of GFP-H2B 3T3 fibroblast cells.

Thermoresponsive nanocomposite double network hydrogels

The utility and efficacy of thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels as smart materials is limited by their physical properties. In this study, we sought to design PNIPAAm nanocomposite hydrogels which displayed enhanced mechanical properties as well as deswelling-reswelling kinetics but without reducing equilibrium swelling or altering the convenient volume phase transition temperature (VPTT) of PNIPAAm. PNIPAAm hydrogels were formed as double networks (DN) comprised of a tightly crosslinked 1st network and a loosely crosslinked 2nd network. In addition, polysiloxane nanoparticles of two different average diameters (~50 nm and ~200 nm) were incorporated during formation of the 1st or 2nd network. The influence of the hydrogel composition on VPTT, morphology, equilibrium swelling, deswelling-reswelling kinetics and mechanical properties was evaluated. We observed that DN hydrogels formed with ~200 nm polysiloxane nanoparticles introduced during formation of the 1st network achieved the best combination of the desired properties.

Shape memory polymers with silicon-containing segments

Thermoresponsive shape memory polymers are stimuli-responsive materials whose shape is modulated by heat. They have been investigated as smart materials in a variety of biomedical, industrial and aerospace applications. The vast majority of shape memory polymers have been limited to those prepared from organic polymers. In this present work, shape memory polymers comprised of inorganic silicon-containing polymer segments (polydimethylsiloxane, PDMS) and organic poly(ε-caprolactone) (PCL) segments were developed. Because of its low T g, PDMS served as a highly effective soft segment. The photochemical cure of diacrylated PCL n -block-PDMS37-block-PCL n macromers with tailored PCL segment lengths produced networks with excellent mechanical properties, shape fixity, and shape recovery.