A comparison of portal vein embolization with poly(2-hydroxyethylmethacrylate) and a histoacryl/lipiodol mixture in patients scheduled for extended right hepatectomy.

To determine whether PHEMA [poly(2-hydroxyethylmethacrylate)] is suitable for portal vein embolization in patients scheduled to right hepatectomy and whether it is as effective as the currently used agent (a histoacryl/lipiodol mixture). Two groups of nine patients each scheduled for extended right hepatectomy for primary or secondary hepatic tumor, had right portal vein embolization in an effort to induce future liver remnant (FLR) hypertrophy. One group had embolization with PHEMA, the other one with the histoacryl/lipiodol mixture. In all patients, embolization was performed using the right retrograde transhepatic access. Embolization was technically successful in all 18 patients, with no complication related to the embolization agent. Eight patients of either group developed FLR hypertrophy allowing extended right hepatectomy. Likewise, one patient in each group had recanalization of a portal vein branch. Histology showed that both embolization agents reach the periphery of portal vein branches, with PHEMA penetrating somewhat deeper into the periphery. PHEMA has been shown to be an agent suitable for embolization in the portal venous system comparable with existing embolization agent (histoacryl/lipiodol mixture).

Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 6: 3D hydrogels with positive and negative surface charges and polyelectrolyte complexes in spinal cord injury repair.

Macroporous hydrogels are artificial biomaterials commonly used in tissue engineering, including central nervous system (CNS) repair. Their physical properties may be modified to improve their adhesion properties and promote tissue regeneration. We implanted four types of hydrogels based on 2-hydroxyethyl methacrylate (HEMA) with different surface charges inside a spinal cord hemisection cavity at the Th8 level in rats. The spinal cords were processed 1 and 6 months after implantation and histologically evaluated. Connective tissue deposition was most abundant in the hydrogels with positively-charged functional groups. Axonal regeneration was promoted in hydrogels carrying charged functional groups; hydrogels with positively charged functional groups showed increased axonal ingrowth into the central parts of the implant. Few astrocytes grew into the hydrogels. Our study shows that HEMA-based hydrogels carrying charged functional groups improve axonal ingrowth inside the implants compared to implants without any charge. Further, positively charged functional groups promote connective tissue infiltration and extended axonal regeneration inside a hydrogel bridge.

Biocompatible hydrogels in spinal cord injury repair.

Spinal cord injury results in a permanent neurological deficit due to tissue damage. Such a lesion is a barrier for "communication" between the brain and peripheral tissues, effectors as well as receptors. One of the primary goals of tissue engineering is to bridge the spinal cord injury and re-establish the damaged connections. Hydrogels are biocompatible implants used in spinal cord injury repair. They can create a permissive environment and bridge the lesion cavities by providing a scaffold for the regeneration of neurons and their axons, glia and other tissue elements. The advantage of using artificial materials is the possibility to modify their physical and chemical properties in order to develop the best implant suitable for spinal cord injury repair. As a result, several types of hydrogels have been tested in experimental studies so far. We review our work that has been done during the last 5 years with various types of hydrogels and their applications in experimental spinal cord injury repair.

Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 4: growth of rat bone marrow stromal cells in three-dimensional hydrogels with positive and negative surface charges and in polyelectrolyte complexes.

The growth of bone marrow stromal cells was assessed in vitro in macroporous hydrogels based on 2-hydro- xyethyl methacrylate (HEMA) copolymers with different electric charges. Copolymers of HEMA with sodium methacrylate (MA(-)) carried a negative electric charge, copolymers of HEMA with [2-(methacryloyloxy)ethyl] trimethylammonium chloride (MOETA(-)) carried a positive electric charge and terpolymers of HEMA, MA(-) and MOETA(+) carried both, positive and negative electric charges. The charges in the polyelectrolyte complexes were shielded by counter-ions. The hydrogels had similar porosities, based on a comparison of their diffusion parameters for small cations as measured by the real-time tetramethylammonium iontophoretic method of diffusion analysis. The cell growth was studied in the peripheral and central regions of the hydrogels at 2 hours and 2, 7, 14 and 28 days after cell seeding. Image analysis revealed the highest cellular density in the HEMA-MOETA(+) copolymers; most of the cells were present in the peripheral region of the hydrogels. A lower density of cells but no difference between the peripheral and central regions was observed in the HEMA-MA(-) copolymers and in polyelectrolyte complexes. This study showed that positively charged functional groups promote the adhesion of cells.

Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part II. Copolymers with positive and negative charges, polyelectrolyte complexes.

Crosslinked macroporous hydrogels based on 2-hydroxyethyl methacrylate (HEMA)-[2-(methacryloyloxy)ethyl]trimethylammonium chloride (MOETACl) copolymer, HEMA-MOETACl-methacrylic acid (MA) terpolymer, and on a polyelectrolyte complex of HEMA-MA copolymer with poly(MOETACl) were prepared. All the hydrogels were prepared in the presence of fractionated sodium chloride particles. The hydrogels were characterized by the number of pores and the total volume of all pores in unit volume, the average volume and the average diameter of single pore. Morphology of the hydrogels was investigated by confocal and scanning electron microscopy. The hydrogels based on polyelectrolyte complexes were also characterized by chemical composition. Homogeneous (non-porous) hydrogels with the same composition as macroporous hydrogels were prepared and characterized by their biocompatibility.

Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part III. Hydrogels as carriers for immobilization of proteins.

Four series of macroporous hydrogels based on crosslinked copolymers of 2-hydroxyethyl methacrylate (HEMA)-sodium methacrylate (MANa), copolymer HEMA-[2-(methacryloyloxy)ethyl]trimethylammonium chloride (MOETACl), terpolymer HEMA-MANa-MOETACl and on a polyelectrolyte complex were used as carriers for immobilization of proteins, chicken egg white albumin and avidin. The adsorption capacity of the hydrogels for the two proteins, kinetics and pH dependence of albumin adsorption and desorption were studied. The morphology of the hydrogels with and without immobilized albumin was studied by low-vacuum scanning electron microscopy.

Development of hydrogel implants for urinary incontinence treatment.

Hydrogel implants for urinary incontinence treatment based on HEMA supplemented with 10% methacrylic acid have been developed. The swelling properties of implants were tested in vitro and in vivo after implantation to laboratory mice. Biocompatibility has been determined by incubation of implants in tissue culture, by histological examination of adjacent tissues after subcutaneous application of implants to laboratory mouse in a long-term experiment, and by flow cytometry examination of blood cells. The swelling of hydrogel implants was completed in 6-24 h. There was no effect on in vitro growth of cells incubated with implants. In mice, implants were well tolerated without any sign of inflammatory reaction. The material allows an elastic compression of urethra compensating a damaged sphincter after trans-urethral sub-mucosal implantation of hydrogel cylinders.

Polymer hydrogels usable for nervous tissue repair.

The implantation of non-resorbable biocompatible polymer hydrogels into defects in the central nervous system can reduce glial scar formation, bridge the lesion and lead to tissue regeneration within the hydrogel. We implanted hydrogels based on crosslinked poly hydroxyethyl-methacrylate (pHEMA) and poly N-(2-hydroxypropyl)-methacrylamide (pHPMA) into the rat cortex and evaluated the cellular invasion into the hydrogels by means of immunohistochemical methods and tetramethylammonium diffusion measurements. Astrocytes and NF160-positive axons grew similarly into both types of hydrogels. We found no cell types other than astrocytes in the pHEMA hydrogels. In the pHPMA hydrogels, we found a massive ingrowth of connective tissue elements. These changes were accompanied by corresponding changes in the extracellular space volume fraction and tortuosity of the hydrogels.