Spinal cord injury (SCI), is a devastating condition leading to the loss of locomotor and sensory function below the injured segment. Despite some progress in acute SCI treatment using stem cells and biomaterials, chronic SCI remains to be addressed. We have assessed the use of laminin-coated hydrogel with dual porosity, seeded with induced pluripotent stem cell-derived neural progenitors (iPSC-NPs), in a rat model of chronic SCI. iPSC-NPs cultured for 3 weeks in hydrogel in vitro were positive for nestin, glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2). These cell-polymer constructs were implanted into a balloon compression lesion, 5 weeks after lesion induction. Animals were behaviorally tested, and spinal cord tissue was immunohistochemically analyzed 28 weeks after SCI. The implanted iPSC-NPs survived in the scaffold for the entire experimental period. Host axons, astrocytes and blood vessels grew into the implant and an increased sprouting of host TH+ fibers was observed in the lesion vicinity. The implantation of iPSC-NP-LHM cell-polymer construct into the chronic SCI led to the integration of material into the injured spinal cord, reduced cavitation and supported the iPSC-NPs survival, but did not result in a statistically significant improvement of locomotor recovery.

• Keywords
• Chronic spinal cord injury, HEMA hydrogel, human induced pluripotent stem cells, laminin, neural progenitors, surface charge,
• MeSH
• Cell Differentiation MeSH
• Chronic Disease MeSH
• Hydrogels MeSH
• Induced Pluripotent Stem Cells metabolism   MeSH
• Rats MeSH
• Neural Stem Cells transplantation   MeSH
• Spinal Cord Injuries therapy   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Hydrogels MeSH

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.

• MeSH
• Biocompatible Materials therapeutic use   MeSH
• Thoracic Vertebrae injuries   pathology   MeSH
• Hydrogels therapeutic use   MeSH
• Rats MeSH
• Methacrylates therapeutic use   MeSH
• Spinal Cord Injuries pathology   therapy   MeSH
• Porosity MeSH
• Rats, Wistar MeSH
• Surface Properties MeSH
• Nerve Regeneration * MeSH
• Guided Tissue Regeneration methods   MeSH
• Static Electricity MeSH
• Materials Testing MeSH
• Treatment Outcome MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biocompatible Materials MeSH
• Hydrogels MeSH
• hydroxyethyl methacrylate MeSH Browser
• Methacrylates MeSH

Infrared attenuated total reflection spectroscopy was used for in situ observation of the deposition of collagen I on poly(2-hydroxyethyl methacrylate-co-methacrylic acid, 2.9%) hydrogels and subsequent attachment of laminin or fibronectin on the collagen surface. While there was no adsorption of collagen dissolved in an acid solution on the hydrogel surface, it deposited on the surface at pH 6.5. The collagen layers with attached laminin or fibronectin were stable on hydrogel surface in physiological solution. The modification with collagen and particularly with collagen and laminin or fibronectin allowed the adhesion and growth of mesenchymal stromal cells and astrocytes on the hydrogel surface.

• MeSH
• Extracellular Matrix Proteins chemistry   MeSH
• Hydrogels chemistry   MeSH
• Hydrogen-Ion Concentration MeSH
• Microscopy, Atomic Force MeSH
• Polyhydroxyethyl Methacrylate analogs & derivatives   chemistry   MeSH
• Surface Properties MeSH
• Spectroscopy, Fourier Transform Infrared MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Extracellular Matrix Proteins MeSH
• Hydrogels MeSH
• polyhydroxyethyl methacrylate hydrogels MeSH Browser
• Polyhydroxyethyl Methacrylate MeSH

Macroporous hydrogels based on 2-hydroxyethyl methacrylate, 2-ethoxyethyl methacrylate and N-(2-hydroxypropyl)methacrylamide, methacrylic acid and [2-(methacryloyloxy)ethyl]trimethylammonium chloride crosslinked with N,O-dimethacryloylhydroxylamine were prepared. Hydrogels were degraded in a buffer of pH 7.4. Completely water-soluble polymers were obtained over time periods ranging from 2 to 40 days. The process of degradation was followed gravimetrically and by optical and electron microscopy. In vivo biological tests with hydrogels based on copolymers of 2-ethoxyethyl methacrylate/N-(2-hydroxypropyl)methacrylamide were performed.

• MeSH
• Biocompatible Materials metabolism   therapeutic use   MeSH
• Hydrogels metabolism   therapeutic use   MeSH
• Hydrolysis MeSH
• Rats MeSH
• Methacrylates metabolism   therapeutic use   MeSH
• Spinal Cord Diseases pathology   therapy   MeSH
• Porosity MeSH
• Rats, Wistar MeSH
• Materials Testing methods   MeSH
• Absorbable Implants * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biocompatible Materials MeSH
• Hydrogels MeSH
• hydroxyethyl methacrylate MeSH Browser
• Methacrylates MeSH

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.

• MeSH
• Biocompatible Materials chemistry   MeSH
• Bone Marrow Cells cytology   MeSH
• Stromal Cells cytology   MeSH
• Time Factors MeSH
• Diffusion MeSH
• Electrolytes chemistry   MeSH
• Femur metabolism   MeSH
• Rats MeSH
• Methacrylates chemistry   MeSH
• Hydrogel, Polyethylene Glycol Dimethacrylate * MeSH
• Image Processing, Computer-Assisted MeSH
• Rats, Wistar MeSH
• Surface Properties MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biocompatible Materials MeSH
• Electrolytes MeSH
• hydroxyethyl methacrylate MeSH Browser
• Methacrylates MeSH
• Hydrogel, Polyethylene Glycol Dimethacrylate * MeSH