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Biomedical subjects

L G Cima

Publications and source records attributed to L G Cima.

7 recordsLinked to original sources

Injectable cartilage.

Slowly polymerizing calcium alginate gels were investigated as a means of delivering large numbers of isolated chondrocytes by means of injection to determine if these gels would promote engraftment and could provide three-dimensional templates for new cartilage growth. Chondrocytes isolated from the articular surface of calf forelimbs were added to a 1% sodium alginate dissolved in a 0.1 M potassium phosphate buffer solution (pH 7.4) to generate a final cellular density of 10 x 10(6)/ml (representing approximately 10 percent of the cellular density of human juvenile articular cartilage). The calcium alginate-chondrocyte mixture was injected through a 22-gauge needle in 100-microliters aliquots under the panniculus carnosus on the dorsum of nude mice and incubated for 6 (n = 4), 8 (n = 11), and 12 (n = 12) weeks in vivo. Time-zero specimens (n = 10) consisting of 100-microliters aliquots of the calcium alginate-chondrocyte mixture were used to calculate initial weight. At harvest, all calcium alginate-chondrocyte specimens exhibited a pearly opalescence and were firm to palpation as early as 6 weeks after injection. By 12 weeks of in vivo incubation, the specimens weighed 0.15 +/- 0.04 gm, significantly more than the initial weight of 0.11 +/- 0.01 gm (p < 0.05). Specimens stained with hematoxylin and eosin demonstrated lacunae within a basophilic ground-glass substance. Control specimens of calcium alginate without chondrocytes (n = 4) had a doughy consistency 12 weeks after injection and had no histologic evidence of cartilage formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alginates

Polymer substrates for controlled biological interactions.

The identification of a myriad of small peptide and carbohydrate ligands recognized by cell surface receptors has generated enthusiasm for the use of these ligands of components of biomaterials for controlling cellular interactions. Achieving control of cell interactions via ligand modification of materials also requires that nonspecific interactions of cells with these materials due to surface adsorption of biological macromolecules is minimized. Polyethylene oxide (PEO) exhibits extraordinary inertness toward most biological macromolecules and is thus receiving increasing attention as a component of new materials for controlling cell behavior. Both surface and bulk modifications with PEO are being applied to develop a range of bland substrate materials as vehicles for ligand immobilization.

Animals

A hydrodynamic interpretation of crisis in sickle cell anemia.

The occurrence of crisis events in patients with sickle cell disease is associated with an increase in blood plasma viscosity, the hydrodynamic consequences of which are examined here. A mathematical model of the flow of sickle cells in capillaries predicts that for moderate increases in plasma viscosity, a regime of multivalued solutions for blood velocities is encountered, and the likely physical response is a precipitous drop to the lowest velocity solution. This behavior results from the coupling of the hydrodynamics with sickle erythrocyte rheology and oxygen transport to the surrounding tissue; no such catastrophe is predicted for normal erythrocytes. The type of velocity changes predicted by the model strongly suggest that plasma viscosity changes may play an important role in initiating or exacerbating crisis.

Anemia, Sickle Cell

Preparation of poly(glycolic acid) bonded fiber structures for cell attachment and transplantation.

A novel method was developed to prepare three-dimensional structures with desired shapes used as templates for cell transplantation. The produced biomaterials are highly porous with large surface/volume and provide the necessary space for attachment and proliferation of the transplanted cells. The processing technique calls for the formation of a composite material with nonbonded fibers embedded in a matrix followed by thermal treatment and the selective dissolution of the matrix. To evaluate the technique, poly(glycolic acid) (PGA) fiber meshes were bonded using poly(L-lactic acid) (PLLA) as a matrix. The bonded structures were highly porous with values of porosity up to 0.81 and area/volume ratios as high as 0.05 micron-1.

Animals

Injectable alginate seeded with chondrocytes as a potential treatment for vesicoureteral reflux.

Injection of polytetrafluoroethylene (Teflon) or collagen has been used in the endoscopic treatment of vesicoureteral reflux. Although the principle of an endoscopic treatment is valid, there are concerns regarding the long-term safety and effectiveness of these substances. The goal of several investigators has been to find alternate implant materials that would be safe for human use. Toward this goal we conducted a study to determine the effect of chondrocytes using a biodegradable polymer solution as a template. Hyaline cartilage was obtained from the articular surfaces of calf shoulders and chondrocytes were harvested. Chondrocyte suspensions were concentrated to 20, 30 and 40 x 10(6) cells per cc and mixed with dry alginate powder (a biodegradable polymer) to form a gel. Twelve athymic mice were injected subcutaneously with a chondrocyte-alginate solution. Each mouse had 4 injection sites, consisting of control, 10, 15 and 20 x 10(6) chondrocyte cells (48 injection sites). Mice were sacrificed at 2, 4, 6 and 12 weeks after injection. Histological examination of the injection sites demonstrated evidence of cartilage formation in 34 of the 36 experimental injection sites. Gross examination of the injection sites with increasing time showed that the polymer gels were progressively replaced by cartilage. The ultimate size of the cartilage formed was related to the initial chondrocyte concentration injected, and appeared to be uniform and stable within each category. There was no evidence of cartilage formation in the 12 controls. Histological analyses of distant organs showed no evidence of cartilage or alginate gel migration, or granuloma formation. In conclusion, chondrocyte-alginate gel suspensions are injectable, appear to be nonmigratory and are able to conserve their volume. In addition, the use of autologous cartilage cells would preclude an immunological reaction. These preliminary studies indicate that autologous cartilage-polymer gel solutions may be potentially useful in the endoscopic treatment of reflux.

Alginates

Tissue engineering by cell transplantation using degradable polymer substrates.

This paper reviews our research in developing novel matrices for cell transplantation using bioresorbable polymers. We focus on applications to liver and cartilage as paradigms for regeneration of metabolic and structural tissue, but review the approach in the context of cell transplantation as a whole. Important engineering issues in the design of successful devices are the surface chemistry and surface microstructure, which influence the ability of the cells to attach, grow, and function normally; the porosity and macroscopic dimensions, which affect the transport of nutrients to the implanted cells; the shape, which may be necessary for proper function in tissues like cartilage; and the choice of implantation site, which may be dictated by the total mass of the implant and which may influence the dimensions of the device by the available vascularity. Studies show that both liver and cartilage cells can be transplanted in small animals using this approach.

Animals

Future directions in biomaterials.

Biomaterials have made a great impact on medicine. However, numerous challenges remain. This paper discusses three representative areas involving important medical problems. First, drug delivery systems; major considerations include drug-polymer interactions, drug transformation, diffusion properties of drugs and, if degradation occurs, of polymer degradation products through polymer matrices developing a more complete understanding of matrix degradation in the case of erodible polymers and developing new engineered polymers designed for specific purposes such as vaccination or pulsatile release. Second, cell-polymer interactions, including the fate of inert polymers, the use of polymers as templates for tissue regeneration and the study of polymers which aid cell transplantation. Third, orthopaedic biomaterials, including basic research in the behaviour of chondrocytes, osteocytes and connective tissue-free interfaces and applied research involving computer-aided design of biomaterials and the creation of orthopaedic biomaterials.

Biocompatible Materials