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Biomedical subjects

K S Anseth

Publications and source records attributed to K S Anseth.

18 recordsLinked to original sources
PubMed2001

Attachment of fibronectin to poly(vinyl alcohol) hydrogels promotes NIH3T3 cell adhesion, proliferation, and migration.

Hydrogels have been used in biology and medicine for many years, and they possess many properties that make them advantageous for tissue engineering applications. Their high water content and tissue-like elasticity are similar to the native extracellular matrix of many tissues. In this work, we investigated the potential of a modified poly(vinyl alcohol) (PVA) hydrogel as a biomaterial for tissue engineering applications. First, the ability of NIH3T3 fibroblast cells to attach to PVA hydrogels was evaluated. Because of PVA's extremely hydrophilic nature, important cell adhesion proteins do not adsorb to PVA hydrogels, and consequently, cells are unable to adhere to the hydrogel. By covalently attaching the important cell adhesion protein fibronectin onto the PVA hydrogel surface, the rate of fibroblast attachment and proliferation was dramatically improved, and promoted two-dimensional cell migration. These studies illustrate that a fibronectin-modified PVA hydrogel is a potential biomaterial for tissue engineering applications.

3T3 Cells↗
PubMed2001

The effects of scaffold thickness on tissue engineered cartilage in photocrosslinked poly(ethylene oxide) hydrogels.

The thickness of human articular cartilage has been reported to vary from less than 0.5 up to 7 mm. Hence, tissue engineered cartilage scaffolds should be able to span the thickness of native cartilage to fill defects of all shapes and sizes. In this study, we demonstrate the potential for using photopolymerization technology to encapsulate chondrocytes in poly(ethylene oxide) hydrogels, which vary in thickness from 2 to 8 mm. Chondrocytes, encapsulated in an 8 mm thick, photocrosslinked hydrogel and cultured in vitro for 6 weeks, remained viable and produced cartilaginous tissue throughout the construct comparable to a 2 mm thick gel as seen both histologically and biochemically. In addition, the total collagen and glycosaminoglycan contents per wet weight of the 8 mm thick cell-polymer construct were 0.13 +/- 0.01 and 0.25 +/- 0.03%, respectively, and did not vary significantly as a function of spatial position in the construct. The histological evidence and the biochemical content were similar in all constructs of varying thickness. The results suggest that photocrosslinked hydrogels are promising scaffolds for tissue engineering cartilage as cell viability is readily maintained; uniform cell seeding is easy to achieve: and the biochemical content of the extracellular matrix is not compromised as the scaffold thickness is increased from 2 to 8 mm.

Animals↗
PubMed2001

Conversion and temperature profiles during the photoinitiated polymerization of thick orthopaedic biomaterials.

Polymerization of a tetrafunctional monomer was investigated under a variety of photoinitiation conditions to assess the ability to form thick materials in situ for orthopaedic applications. The major biological concerns include local cell and tissue necrosis due to the polymerization exotherm and low conversions at greater depths due to light attenuation through thick samples. Experimental results indicate that depth of cure and temperature rises are controllable by altering the photoinitiator concentration, initiating light intensity, and type of photoinitiator. For example, no measurable conversion was detected at a 1.0 cm depth when polymerization was initiated with 1.0 wt% DMPA and 100 mW/cm2 ultraviolet light, whereas approximately 40% conversion was obtained when the initiator concentration was lowered to 0.1 wt%. This conversion was further increased to approximately 55% when a photobleaching initiator system was employed. At the highest rate of initiation studied (i.e., 1.0 wt% DMPA irradiated with 100 mW/cm2 ultraviolet light), a maximum temperature of approximately 49 degrees C was reached at the sample surface; however, this temperature dramatically decreased to approximately 33 degrees C when the light intensity was decreased to 25 mW/cm2. Finally, dual initiating systems that synergistically combine the advantages of photoinitiation and thermal initiation were investigated.

Biocompatible Materials↗
PubMed2001

Photopolymerized biomaterials for application in the temporomandibular joint.

Chronic foreign body reactions have limited the successful application of alloplastic implants for treatment of temporomandibular joint (TMJ) disorders. There is a great clinical need for new materials with enhanced properties for application in the diarthrodial joint. Photopolymerizations may provide many advantages for fabricating new biomaterials for the TMJ and may address some of the notable differences between the TMJ and other articulations. Specifically, the feasibility of trans-tissue (i.e. through the skin) photopolymerizations may yield less-invasive surgical procedures. Also, novel 3-dimensional photoprocessing techniques may be used to fabricate patient-specific alloplastic devices for improved compliance and efficacy. Finally, the mild conditions necessary for photopolymerizations make the reaction ideal for encapsulating cells with the potential to create constructs for tissue engineering, which may be beneficial for disk replacement therapies.

Animals↗
PubMed2001

In situ forming lactic acid based orthopaedic biomaterials: influence of oligomer chemistry on osteoblast attachment and function.

The ability of osteoblasts to attach and function normally on scaffolds fabricated from synthetic materials is essential for musculoskeletal tissue engineering applications. In this study, the osteoconductivity of polymer networks formed from multifunctional lactic acid oligomers was assessed. These oligomers form highly crosslinked networks via a photoinitiated polymerization, which provides potential advantages for many orthopaedic applications. Depending on the initial oligomer chemistry and the resultant polymer hydrophobicity, protein adsorption and osteoblast function varied significantly between the various lactic acid based polymer chemistries. Results were compared to control polymers of tissue culture polystyrene (TCPS) and 50:50 poly(lactic-co-glycolic acid) (PLGA). The viability of osteoblasts attached to poly(2EG10LA) and poly(2EG6LA) was close to the TCPS and PLGA after 7 and 14 days of culture, whereas cell viability was approximately 50% lower on poly(8EG6LA). Additionally, the alkaline phosphatase activity and mineralization of attached osteoblasts were similar on poly(2EG10LA) and PLGA, whereas these markers of bone formation were significantly lower for poly(2EG6LA) and poly(8EG6LA). For example, the alkaline phosphatase activity of rat calvarial osteoblasts attached to poly(2EG10LA) was 0.048 +/- 0.006 micromol mg(-1) protein-min, but only 0.030 +/- 0.003 micromol mg(-1) protein-min for osteoblasts attached to poly(8EG6LA) after 14 days of culture. Finally, osteoblasts were seeded onto three-dimensional scaffolds to demonstrate the applicability of the scaffolds for bone tissue engineering.

Adsorption↗
PubMed2000

Surface and bulk modifications to photocrosslinked polyanhydrides to control degradation behavior.

A unique class of surface-eroding polyanhydrides was developed and explored for use in medical applications requiring high-strength biomaterials (e.g., orthopedics). In particular, dimethacrylated anhydride monomers were synthesized that photopolymerize quickly to render densely crosslinked polymer networks that degrade from the surface only by hydrolysis of labile anhydride linkages. Previous research on these materials has shown that the rate of hydrolysis of the degradable linkages is dependent on the hydrophobicity of the network composition. This article demonstrates the versatility in controlling the degradation process and resulting cellular response in these materials through the incorporation of new chemistries and the formation of polymer-polymer composite structures. Specifically, the rate of mass loss was controlled by the addition of hydrophobic linear polymers [e.g., poly(methyl methacrylate)] or monovinyl monomers based on hydrophobic natural components (e.g., cholesterol, steric acid). In addition, a newly established photografting method was used to modify the network surface chemistry with cholesterol- and stearic acid-based polymer grafts to control the degradation front and cellular interactions at the polymer-tissue interface. Finally, a porogen leaching method was used to form porous polyanhydride constructs, which can be subsequently filled with osteoblasts photoencapsulated in a hydrogel, as potential synthetic allograft materials for tissue engineering bone.

Anhydrides↗
PubMed2000

Photopolymerized, multilaminated matrix devices with optimized nonuniform initial concentration profiles to control drug release.

This paper describes a novel approach to obtain desired release profiles from diffusion-controlled matrix devices by employing nonuniform initial concentration profiles theoretically and experimentally. Theoretically, a model was developed to examine the effect of nonuniform initial concentration profiles on matrix release behavior, and an optimization technique was investigated to determine suitable nonuniform initial concentration profiles which provide desired release patterns. Experimentally, release rates of an organic dye from photopolymerized matrix devices were measured to test the application of these mathematical techniques and the efficacy of photolaminated matrices in approximating the optimized release behavior. All system parameters were measured by independent experiments, and the experimental release data agree very well with the computed results.

Acrylates↗
PubMed2000

Photopolymers in orthopedics: characterization of novel crosslinked polyanhydrides.

Novel, high modulus, degradable polymers were prepared from methacrylated anhydride monomers of tricarballylic acid (MTCA) and pyromellitylimidoalanine (MPMA-ala). Kinetic studies indicate that the time scale of photopolymerization of MTCA (< 30 s) is suitable for in vivo applications. Additionally, the tensile modulus of copolymers of these novel monomers with methacrylic anhydride (MA) ranged from 0.8 to 2.1 GPa, which lies between the modulus of trabecular and cortical bone. Degradation studies indicate that the copolymers of MTCA and MPMA-ala with MA are initially surface degrading, which is important to maintaining polymer strength through the degradation process. Monomers such as these that can be rapidly polymerized using ultraviolet or blue light into high modulus degradable materials have great potential in orthopedics.

Anhydrides↗
PubMed2000

A review of photocrosslinked polyanhydrides: in situ forming degradable networks.

Many orthopaedic injuries could benefit from a high-strength and degradable material with good tissue compatibility. In addition, there is a great clinical need for materials which are easily contoured or placed into complex-shaped defects by a surgeon. We have rationally designed a new class of photocrosslinkable polyanhydride monomers which in situ form high-strength and surface eroding networks of complex geometries. This paper highlights the advantages of these materials for orthopaedic applications and the technique of photopolymerization for reacting these monomers under physiological conditions. The rationale for the material design, photopolymerization kinetics, degradation behavior, and histology in subcutaneous tissue and a model bone defect are presented.

Anhydrides↗
PubMed2000

Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro.

This work investigates the cytocompatibility of several photoinitiating systems for potential cell encapsulation applications. Both UV and visible light initiating schemes were examined. The UV photoinitiators included 2,2-dimethoxy-2-phenylacetophenone (Irgacure 651), 1-hydroxycyclohexyl phenyl ketone (Irgacure 184), 2-methyl-1-[4-(methylthio) phenyl]-2-(4-morpholinyl)-1-propanone (Irgacure 907), and 2-hydroxy-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone (Darocur 2959). The visible light initiating systems included camphorquinone (CQ) with ethyl 4-N,N-dimethylaminobenzoate (4EDMAB) and triethanolamine (TEA) and the photosensitizer isopropyl thioxanthone. A cultured fibroblast cell line, NIH/3T3, was exposed to the photoinitiators at varying concentrations from 0.01% (w/w) to 0.1% (w/w) with and without the presence of initiating light. The results demonstrated that at low photoinitiator concentrations (< or = 0.01% (w/w)), all of the initiator molecules were cytocompatible with the exception of CQ, Irgacure 651, and 4EDMAB which had a relative survival approximately 50% lower than a control. In the presence of low intensity initiating light (approximately 6 mWcm(-2) of 365 nm UV light and approximately 60 mWcm(-2) of 470-490 nm visible light) and initiating radicals, Darocur 2959 at concentrations < or = 0.05% (w/w) and CQ at concentrations < or = 0.01% (w/w) were the most promising cytocompatible UV and visible light initiating systems, respectively. To demonstrate the potential use of cytocompatible photoinitiating systems in cell encapsulation applications, chondrocytes were encapsulated in a photocrosslinked hydrogel using 0.05% (w/w) Darocur 2959 (cytocompatible) and 0.01% (w/w) Irgacure 651 (cyto-incompatible). After photopolymerizing for 10 minutes with approximately 8 mWcm(-2) of 365 nm light, nearly all the chondrocytes survived the process with Darocur 2959 while very few of the chondrocytes survived the process with Irgacure 651.

3T3 Cells↗
PubMed1999

Photopolymerization of multilaminated poly(HEMA) hydrogels for controlled release.

A novel approach to immobilize nonuniform initial drug concentration profiles in multilaminated matrix devices utilizing photopolymerization techniques is presented. Solution polymerization of 2-hydroxyethyl methacrylate (HEMA) and diethylene glycol dimethacrylate (DEGDMA) in the presence of a model compound, acid orange 8 (AO8), was conducted using UV light and photoinitiators to construct a laminated matrix device. In this process, each layer was polymerized with a different AO8 concentration to form a nonuniform initial concentration profile in the matrix devices. The AO8 diffusion coefficients measured in this work were used in a concurrently developed model to predict the effects of nonuniform AO8 concentration profiles on AO8 release patterns. The release data predicted by the model agreed well with the experimentally determined data. The results indicate that a zero-order release pattern can be approximated by employing a suitable nonuniform initial drug concentration profile.

Acrylates↗
PubMed1999

Crosslinked polyanhydrides for use in orthopedic applications: degradation behavior and mechanics.

High-strength, surface-eroding polymers were synthesized from methacrylated anhydride monomers of sebacic acid (MSA) and 1,6-bis(carboxyphenoxy) hexane (MCPH). These multifunctional monomers were photopolymerized using ultraviolet light to produce highly crosslinked polyanhydride networks. Through this approach, the crosslinking density of the resulting polymer network was used to control the final mechanical properties, while the degradation time scale was controlled by the chemical composition of the network. The combined hydrophobicity of the polymer backbone with the hydrolytically labile anhydride linkages led to surface-eroding networks, as confirmed by linear cumulative mass loss profiles as a function of degradation time for crosslinked polymer disks. By copolymerizing varying amounts of MSA and MCPH, the degradation rate of the final network was controlled from 2 days to 1 year. The tensile modulus of crosslinked poly(MSA) (1.4 GPa) was nearly an order of magnitude larger than that of linear poly(sebacic acid). In general, the mechanical properties of the crosslinked polyanhydrides networks were within ranges of those reported for cortical and trabecular bone. However, unlike bulk degrading polyesters such as poly(lactic acid), these surface eroding networks maintained >70% of their tensile modulus with 50% mass degradation.

Acrylic Resins↗
PubMed1999

Photopolymerizable degradable polyanhydrides with osteocompatibility.

We have developed a new family of photopolymerizable, methacrylated anhydride monomers and oligomers that combine high strength, controlled degradation, and photoprocessibility in a singular system. Networks with degradation times ranging from 1 week to nearly 1 year and that retain up to 90% of their tensile modulus at 40% mass loss are attainable. In vivo studies in rats have shown that these networks possess excellent osteocompatibility. These combined properties could offer many advantages in medical applications ranging from dentistry to orthopedics.

Anhydrides↗
PubMed1999

The effects of crosslinking density on cartilage formation in photocrosslinkable hydrogels.

Photoencapsulation of chondrocytes to produce tissue engineered cartilage provides many benefits including rapid polymerization times, the ability to fabricate complex architectures in vivo, and spatial and temporal control during polymerization. Recently, we have examined the cytocompatibility of several photoinitiation schemes and found that low photoinitiator concentrations and light intensities in the ultraviolet and visible range are cytocompatible. In this work, we are currently investigating photocrosslinkable hydrogels based on poly(vinyl alcohol) (PVA) and poly(ethylene oxide) (PEO) as scaffolds for tissue engineering cartilage. In particular, the influence of the network crosslinking density, swelling ratio, and chemical composition on the ability of encapsulated chondrocytes to form extracellular matrix is examined. The cartilage produced in these hydrogels will be quantified using biochemical assays that measure DNA content and the amount of sulfated glycosaminoglycans and total collagen in the extracellular matrix. We have demonstrated that chondrocytes encapsulated in a polymer scaffold made from a 20 wt% solution of PEODM/PEO (40 wt% dimethacrylated PEO (MW 3400)/60 wt% PEO (MW 100 K)) form cartilage, and after four weeks the results based on the wet weight of cartilage were approximately 0.03 million cells/mg cartilage, approximately 1.5% glycosaminoglycans and approximately 4.5% total collagen.

Biomedical Engineering↗
PubMed1999

Fundamental studies of biodegradable hydrogels as cartilage replacement materials.

Through intelligent control of monomer chemistry and gelling techniques, biodegradable hydrogels with a range of mechanical strengths and degradation timescales have been constructed. A diacrylated, copoly(ethylene glycol-b-dl-lactic acid) (PEG-b-PLA) macromer was used to produce synthetic networks with equilibrium water contents (EWC) above 70% and initial compressive moduli values exceeding 1 MPa, demonstrating its viability as a cartilage replacement material. Experiments have shown that the mechanical strengths, EWCs, and useful lifetimes of these water-swellable networks are coupled to their copolymer chemistry as well as their processing conditions. A systematic study utilizing photopolymerized gels has been undertaken to elucidate the controlling factors behind the bulk-degradation process, as well as monitor changes in network structure with degradation. A statistical model will be used in conjunction with the experimental data to explain the exponential modulus decay and complex mass loss behavior observed during degradation for these hydrogels.

Biocompatible Materials↗
PubMed1996

Mucoadhesive poly(vinyl alcohol) hydrogels produced by freezing/thawing processes: applications in the development of wound healing systems.

Ultrapure poly(vinyl alcohol) (PVA) hydrogels were prepared by exposing an aqueous solution of 15 or 20 wt% PVA to repeated cycles of freezing for 6 or 12 h at -20 degrees C and thawing for 2 hours at 25 degrees C. The adhesive characteristics of the PVA gels in contact with a reconstituted mucus surface were quantified using a tensile technique. As the number of freezing/thawing cycles increased, the work of fracture (adhesion) decreased due to the increase in the PVA degree of crystallinity. Crystallinity was determined using differential scanning calorimetry. PVA gels prepared from the 20 wt% solution and exposed to two cycles of freezing/thawing exhibited the largest work of adhesion. Drug delivery studies were conducted with ketanserin, a wound healing enhancer. Release studies were conducted using PVA samples prepared from a 20-wt% solution that were exposed to two or three freezing cycles for 12 h followed by thawing for 2 h. Results from the release of the drug from the PVA sample exposed to two cycles showed that approximately 80% of the ketanserin was released within 4 h.

Adhesiveness↗
PubMed1996

The influence of comonomer composition on dimethacrylate resin properties for dental composites.

During the polymerization of multifunctional monomers for dental restorations, typical final double-bond conversions range from 55 to 75%. The low conversion results in a large amount of extractable monomer, reduced adhesion to the filler, and the potential for increased swelling. In this work, the ability to increase the maximum conversion by optimizing the copolymer composition is explored. A series of multi-ethylene glycol dimethacrylate monomers of various lengths was used as a model system to determine how the copolymer composition affects the final conversion, the mechanical properties, and the predicted shrinkage. It was found that the ultimate conversion can be significantly increased, shrinkage decreased, and mechanical properties maintained. It was found that up to 30 wt% of poly(ethylene glycol) 600 dimethacrylate could be added to diethylene glycol dimethacrylate without reducing the strength and increasing the conversion. Results for other comonomer combinations were similar.

Acrylates↗