Spinal cord injury (SCI) is a serious trauma, which often results in a permanent loss of motor and sensory functions, pain and spasticity. Despite extensive research, there is currently no available therapy that would restore the lost functions after SCI in human patients. Advanced treatments use regenerative medicine or its combination with various interdisciplinary approaches such as tissue engineering or biophysical methods. This review summarizes and critically discusses the research from specific interdisciplinary fields in SCI treatment such as the development of biomaterials as scaffolds for tissue repair, and using a magnetic field for targeted cell delivery. We compare the treatment effects of synthetic non-degradable methacrylate-based hydrogels and biodegradable biological scaffolds based on extracellular matrix. The systems using magnetic fields for magnetically guided delivery of stem cells loaded with magnetic nanoparticles into the lesion site are then suggested and discussed.

• Keywords
• Biomaterials, Cell delivery, Hydrogel, Magnetic field, Spinal cord injury,
• MeSH
• Biocompatible Materials pharmacology   therapeutic use   MeSH
• Hydrogels therapeutic use   MeSH
• Humans MeSH
• Magnetic Field Therapy methods   trends   MeSH
• Spinal Cord Injuries physiopathology   therapy   MeSH
• Nerve Regeneration drug effects   physiology   MeSH
• Stem Cell Transplantation methods   trends   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Biocompatible Materials MeSH
• Hydrogels MeSH

Methacrylate hydrogels have been extensively used as bridging scaffolds in experimental spinal cord injury (SCI) research. As synthetic materials, they can be modified, which leads to improved bridging of the lesion. Fibronectin, a glycoprotein of the extracellular matrix produced by reactive astrocytes after SCI, is known to promote cell adhesion. We implanted 3 methacrylate hydrogels: a scaffold based on hydroxypropylmethacrylamid (HPMA), 2-hydroxyethylmethacrylate (HEMA) and a HEMA hydrogel with an attached fibronectin (HEMA-Fn) in an experimental model of acute SCI in rats. The animals underwent functional evaluation once a week and the spinal cords were histologically assessed 3 months after hydrogel implantation. We found that both the HPMA and the HEMA-Fn hydrogel scaffolds lead to partial sensory improvement compared to control animals and animals treated with plain HEMA scaffold. The HPMA scaffold showed an increased connective tissue infiltration compared to plain HEMA hydrogels. There was a tendency towards connective tissue infiltration and higher blood vessel ingrowth in the HEMA-Fn scaffold. HPMA hydrogels showed a significantly increased axonal ingrowth compared to HEMA-Fn and plain HEMA; while there were some neurofilaments in the peripheral as well as the central region of the HEMA-Fn scaffold, no neurofilaments were found in plain HEMA hydrogels. In conclusion, HPMA hydrogel as well as the HEMA-Fn scaffold showed better bridging qualities compared to the plain HEMA hydrogel, which resulted in very limited partial sensory improvement.

• Keywords
• connective tissue, hydrogel, locomotor test, neurofilaments, plantar test, spinal cord injury,
• MeSH
• Axons physiology   MeSH
• Biocompatible Materials MeSH
• Biomarkers MeSH
• Gene Expression MeSH
• Extracellular Matrix metabolism   MeSH
• Neovascularization, Physiologic MeSH
• Blood-Brain Barrier metabolism   MeSH
• Wound Healing MeSH
• Hydrogels * MeSH
• Rats MeSH
• Methacrylates * chemistry   MeSH
• Disease Models, Animal MeSH
• Connective Tissue MeSH
• Spinal Cord Injuries etiology   metabolism   pathology   therapy   MeSH
• Nerve Regeneration * MeSH
• Tissue Scaffolds MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biocompatible Materials MeSH
• Biomarkers MeSH
• Hydrogels * MeSH
• Methacrylates * MeSH

While many types of biomaterials have been evaluated in experimental spinal cord injury (SCI) research, little is known about the time-related dynamics of the tissue infiltration of these scaffolds. We analyzed the ingrowth of connective tissue, axons and blood vessels inside the superporous poly (2-hydroxyethyl methacrylate) hydrogel with oriented pores. The hydrogels, either plain or seeded with mesenchymal stem cells (MSCs), were implanted in spinal cord transection at the level of Th8. The animals were sacrificed at days 2, 7, 14, 28, 49 and 6 months after SCI and histologically evaluated. We found that within the first week, the hydrogels were already infiltrated with connective tissue and blood vessels, which remained stable for the next 6 weeks. Axons slowly and gradually infiltrated the hydrogel within the first month, after which the numbers became stable. Six months after SCI we observed rare axons crossing the hydrogel bridge and infiltrating the caudal stump. There was no difference in the tissue infiltration between the plain hydrogels and those seeded with MSCs. We conclude that while connective tissue and blood vessels quickly infiltrate the scaffold within the first week, axons show a rather gradual infiltration over the first month, and this is not facilitated by the presence of MSCs inside the hydrogel pores. Further research which is focused on the permissive micro-environment of the hydrogel scaffold is needed, to promote continuous and long-lasting tissue regeneration across the spinal cord lesion.

• MeSH
• Axons pathology   MeSH
• Biocompatible Materials chemistry   MeSH
• Time Factors MeSH
• Neovascularization, Physiologic MeSH
• Hydrogels MeSH
• Rats MeSH
• Oligopeptides chemistry   MeSH
• Polyhydroxyethyl Methacrylate chemistry   MeSH
• Spinal Cord Injuries pathology   physiopathology   therapy   MeSH
• Porosity MeSH
• Rats, Wistar MeSH
• Spinal Cord Regeneration physiology   MeSH
• Materials Testing MeSH
• Tissue Scaffolds chemistry   MeSH
• Mesenchymal Stem Cell Transplantation * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH
• Names of Substances
• Biocompatible Materials MeSH
• Hydrogels MeSH
• Oligopeptides MeSH
• Polyhydroxyethyl Methacrylate MeSH
• seryl-isoleucyl-lysyl-valyl-alanyl-valinamide MeSH Browser

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