Production of marked prolongation of islet xenograft survival (rat to mouse) by local release of mouse and rat antilymphocyte sera at transplant site.

Polymer rods impregnated with lyophilized particles of mouse (M) or rat (R) antilymphocyte serum (ALS) were placed adjacent to rat islet xenografts transplanted beneath the kidney capsule of diabetic mice. Insertion of rods containing only MALS or RALS had no effect on the survival time of the rat islet xenografts. In contrast, the insertion of both MALS and RALS rods with the graft produced a marked prolongation of islet xenograft survival (mean survival time greater than 55.

Long-term cross-species brain transplantation of a polymer-encapsulated dopamine-secreting cell line.

Cross-species transplantation of dopamine-releasing cell lines protected against immune rejection by a semi-permeable synthetic membrane may provide a source of neurotransmitters for the treatment of Parkinson's disease. Experiments were carried out to assess whether polymer-encapsulated PC12 cells, a catecholaminergic cell line derived from a rat pheochromocytoma, could survive in vitro as well as in vivo after implantation in the striatum of adult guinea pigs. When maintained in vitro, the encapsulated PC12 cells exhibited good survival, proliferated, and spontaneously released dopamine for at least 6 months.

Influence of surface texture of polymeric sheets on peripheral nerve regeneration in a two-compartment guidance system.

Synthetic guidance channels are useful tools to study the mechanisms underlying peripheral nerve regeneration. In the present study, the lumen of silicone elastomer tubes was divided into two compartments by a polymer strip 10 mm long placed along the tube length. The influence of varying the surface texture of hydrophilic and hydrophobic polymer strips on the morphology of the regenerated neural tissue was analysed.

Macroencapsulation of dopamine-secreting cells by coextrusion with an organic polymer solution.

A new method of coextruding living cells in the core of a forming hollow fibre is described. PC12 cells, an immortalized cell line which secretes large amounts of dopamine, and dissociated bovine adrenal chromaffin cells, a non-dividing cell type which also secretes dopamine, were coextruded by a dry-jet wet spinning technique through a double-lumen spinneret from a 15% weight by volume solution of poly(acrylonitrile vinyl chloride) in either dimethylsulphoxide (DMSO), dimethylacetamide (DMAC) or dimethylformamide (DMF). Closure of the fibre was achieved by mounting polytetrafluoroethylene tubes on a rotating coaxial wheel system which squeezed the forming hollow fibre at regular intervals.

The morphology of regenerating peripheral nerves is modulated by the surface microgeometry of polymeric guidance channels.

The present study was designed to evaluate the influence of synthetic guidance channel surface microgeometry on morphological patterns of neural regeneration. Tubes with smooth (S), rough (R), or alternating smooth-rough (S/R) or rough-smooth (R/S) inner surfaces but with identical chemical composition and permeability characteristics were used to bridge a 4-mm nerve gap in a transected mouse sciatic nerve. Animals received S and R channels for 1, 2 and 4 weeks and both S/R and R/S channels for 2 and 4 weeks.

NGF released from a polymer matrix prevents loss of ChAT expression in basal forebrain neurons following a fimbria-fornix lesion.

Following a unilateral fimbria-fornix lesion, the delivery of nerve growth factor (NGF) to the ipsilateral lateral ventricle of the rat can prevent the lesion-induced loss of choline acetyltransferase (ChAT) expression in the ipsilateral medial septum and vertical diagonal band region. In the present study, the ability of polymer rods to deliver NGF and to prevent a decrease in basal forebrain ChAT expression following a fimbria-fornix lesion was assessed. NGF was loaded into an ethylene vinyl acetate copolymer (EVAc) rod, fabricated by a melt-extrusion process.

Transport functions in a bioartificial kidney under uremic conditions.

A bioartifical kidney, a confluent monolayer of renal tubular cells attached to a permselective synthetic membrane, may some day substitute for the failing renal function. In such a device, the cells would have to exhibit transport properties when exposed to uremic plasma. To test the feasibility of a bioartificial kidney, LLC-PK1 cells derived from the proximal tubule were grown to confluence on microporous, cellulose nitrate membranes and transepithelial transport of inulin, glucose and tetraethylammonium (TEA) was investigated with standard tissue culture medium and with the hemofiltrate obtained from a uremic patient.

Effects of attachment substrates on the growth and differentiation of LLC-PK1 cells.

The growth and differentiation of an established renal epithelial cell line, LLC-PK1, on membrane bound mussel adhesive protein (MAP), collagen, and extracellular matrix (ECM) in serum-containing medium was studied. Cell attachment and growth on uncoated- vs. protein-coated cellulose nitrate and acetate membranes did not differ significantly, and confluence was achieved on all membranes.

Polymer encapsulated dopaminergic cell lines as "alternative neural grafts".

Our preliminary findings (Jaeger et al., 1988; Aebischer et al., 1989; Tresco et al.

Peripheral nerve regeneration through blind-ended semipermeable guidance channels: effect of the molecular weight cutoff.

Synthetic nerve guidance channels are used to better understand the cellular and molecular events controlling peripheral nerve regeneration. In the present study, the contribution of wound-healing molecules to peripheral nerve regeneration was assessed by varying the molecular weight cutoff of the tubular membrane. Nerve regeneration through polysulfone tubular membranes with molecular weight (Mw) cutoffs of 10(5) and 10(6) Da was analyzed in a transected hamster sciatic nerve model.

An encapsulated dopamine-releasing polymer alleviates experimental parkinsonism in rats.

The effect of sustained intrastriatal release of dopamine (DA) from polymer matrices on apomorphine-induced turning behavior in a 6-hydroxydopamine (6-OHDA) unilaterally lesioned rat model was analyzed. A biocompatible semipermeable tube was placed in a denervated striatum as a receptacle for DA-releasing polymer rods. In vitro kinetics showed sustained release of DA from a polymeric rod for 15 days.

Basic fibroblast growth factor released from synthetic guidance channels facilitates peripheral nerve regeneration across long nerve gaps.

Basic fibroblast growth factor (b-FGF) has been shown to enhance the in vitro survival and neurite extension of various types of neurons including dorsal root ganglia (DRG) cells. Alpha-1 glycoprotein (alpha 1-GP), an acute phase reactant, has been reported to enhance the in vitro neuritic extensions of chick DRG cells. In the present study, we investigated the ability of synthetic nerve guidance channels, which release sustained controlled amounts of b-FGF and/or alpha 1-GP, to support the regeneration of a transected peripheral nerve over a 15 mm long gap, a distance that does not permit regeneration in conventional polymeric tubes.

Tissue reaction to intraperitoneal polymer implants: species difference and effects of corticoid and doxorubicin.

The peritoneal cavity is a convenient site for implantation of encapsulated hormone-secreting tissue. However, host tissue organization around such implants may affect solute exchange and viability of the encapsulated tissue. The reaction to polyvinyl chloride acrylic copolymer capsules implanted in the peritoneal cavity of rats and mice was therefore studied.

Control of water flux in a bioartificial kidney.

UC-PK1 cells were grown to confluence on microporous microcellulose membranes in order to test the feasibility of using transmembrane pressure (TMP) for controlling connective water transport in a bioartificial kidney. TMP was applied on either the apical or basal aspect of the polarized cell layer, while the fluid compartments on both sides of the membrane were perfused with tissue culture medium in a miniature flow chamber. The cell monolayer did not allow filtration in the apical to basal direction when positive TMP up to 30 mmHg was applied on the apical side.

Polymer electret guidance channels enhance peripheral nerve regeneration in mice.

Polytetrafluoroethylene (PTFE) tubes were prepared as electrets displaying a quasi-permanent surface charge due to the presence of trapped monopolar charge carriers. PTFE tubes containing either positive or negative charges and electrically neutral PTFE tubes were used as nerve guidance channels for the repair of a 4 mm nerve gap in the sciatic nerve of mice. After 4 weeks of implantation, positively and negatively charged PTFE electrets contained regenerated nerves with significantly more myelinated axons than nerves regenerated in uncharged PTFE tubes.

Renal epithelial-cell-controlled solute transport across permeable membranes as the foundation for a bioartificial kidney.

Despite the success of current blood purification techniques in allowing the survival of individuals with acute and chronic renal failure, the quality of life of people affected by end-stage renal disease remains unsatisfactory. Part of the reason is due to the nonphysiologic manner in which current blood purification techniques achieve homeostasis. Attempts to improve mechanical substitution of renal function by coupling the transport capability of living cells with conventional hemofiltration devices constitute the first step toward the development of an implantable bioartificial kidney.

Brain tissue reaction to permselective polymer capsules.

The brain tissue reaction to permselective polymer capsules implanted in rats was evaluated for 1 to 54 weeks. The polymer capsules were well tolerated in all animals and no recognizable neurological or behavioral deficits were associated with the implants. Necrosis at the brain/polymer interface, as assessed with Nissl stain, was not observed.

Encapsulated thymic epithelial cells as a potential treatment for immunodeficiencies.

The epithelial cells of the thymus produce hormones that have been implicated in the maturation of T lymphocytes. Thymic epithelial cells can be encapsulated in a permselective polymer membrane that allows the passage of thymic hormones, but prevents the entry of antibodies, complement, cells, and viruses. A pure culture of thymic epithelial cells, identified as such by transmission electron microscopy and keratin staining, was obtained by low temperature organ culture of fetal mouse thymus.

Cellular control of membrane permeability. Implications for a bioartificial renal tubule.

A hemofiltrate processor, which consists of a cultured monolayer of renal epithelial cells on a permeable membrane, displayed transport functions that mimicked the renal tubule. Two cell lines, LLC-PK1 (a proximal tubule-like cell) and MDCK (a distal tubule-like cell), were cultured on microporous cellulose nitrate membranes and studied in a diffusion chamber. Dual-label tracer experiments revealed that inulin, glucose, and para-aminohippurate (PAH) moved across unseeded membranes with similar rates in either direction.

Blind-ended semipermeable guidance channels support peripheral nerve regeneration in the absence of a distal nerve stump.

The presence of a distal nerve segment is considered to be essential for peripheral nerve regeneration through impermeable synthetic guidance channels. The use of a perm-selective material may provide a more appropriate regenerating environment by allowing solute exchange across the wall of the channel. We compared perm-selective acrylic copolymer (AC) channels with impermeable silicone elastomer (SE) channels in terms of regeneration in the absence of a distal nerve stump.

Transplantation of neural tissue in polymer capsules.

Neural tissue reaction to permselective polymer capsules and the feasibility of encapsulated neural tissue transplantation were evaluated in a rat model for a period of 1-12 weeks. Polymer implants in the central nervous system were generally well tolerated. The brain reaction to the synthetic material was minimal and did not disturb normal brain architectonics.

Experience with fully bioresorbable aortic grafts in the dog.

Reorganization of the arterial wall through natural processes on the resorption of a totally bioresorbable graft was investigated in dogs with Vicryl prostheses coated with two different blends of bioresorbable polyesters capable of slowing down considerably the disintegration of a Vicryl fabric in vivo. The prostheses (8 to 9 mm in internal diameter, 8 to 10 cm long) were implanted in the infrarenal aortic position for up to 24 weeks. All 18 animals implanted with coated prostheses survived, whereas one animal implanted with an uncoated Vicryl prosthesis died because of early rupture of the graft.

Tissue reaction to fabrics coated with turbostratic carbon: subcutaneous versus vascular implants.

A technique allowing the deposition of an adherent thin film of turbostratic, high-density carbon on heat-sensitive polymers was recently developed. The biological response to this biomaterial on yarns and fabrics of the type used in cardiovascular surgery has been studied. Polyester yarns, knitted Dacron sheets and knitted uncrimped Dacron vascular grafts were coated with a thin film (less than 1 micron) of turbostratic carbon using a physical vapour deposition process.

Piezoelectric guidance channels enhance regeneration in the mouse sciatic nerve after axotomy.

Piezoelectric nerve guidance channels made of polyvinylidene fluoride (PVDF) were evaluated in a transected mouse sciatic nerve model. Poled PVDF channels were compared to unpoled PVDF channels after 4 and 12 weeks of implantation. In all animals, the proximal and distal nerve stumps were bridged by a continuous nerve cable.