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

Restoration of lost neuronal function after spinal cord injury (SCI) still remains a big challenge for current medicine. One important repair strategy is bridging the SCI lesion with a supportive and stimulatory milieu that would enable axonal rewiring. Injectable extracellular matrix (ECM)-derived hydrogels have been recently reported to have neurotrophic potential in vitro. In this study, we evaluated the presumed neuroregenerative properties of ECM hydrogels in vivo in the acute model of SCI. ECM hydrogels were prepared by decellularization of porcine spinal cord (SC) or porcine urinary bladder (UB), and injected into a spinal cord hemisection cavity. Histological analysis and real-time qPCR were performed at 2, 4, and 8 weeks postinjection. Both types of hydrogels integrated into the lesion and stimulated neovascularization and axonal ingrowth into the lesion. On the other hand, massive infiltration of macrophages into the lesion and rapid hydrogel degradation did not prevent cyst formation, which progressively developed over 8 weeks. No significant differences were found between SC-ECM and UB-ECM. Gene expression analysis revealed significant downregulation of genes related to immune response and inflammation in both hydrogel types at 2 weeks post SCI. A combination of human mesenchymal stem cells with SC-ECM did not further promote ingrowth of axons and blood vessels into the lesion, when compared with the SC-ECM hydrogel alone. In conclusion, both ECM hydrogels bridged the lesion cavity, modulated the innate immune response, and provided the benefit of a stimulatory substrate for in vivo neural tissue regeneration. However, fast hydrogel degradation might be a limiting factor for the use of native ECM hydrogels in the treatment of acute SCI.

• MeSH
• Extracellular Matrix * MeSH
• Heterografts MeSH
• Hydrogels pharmacology   MeSH
• Humans MeSH
• Mesenchymal Stem Cells metabolism   MeSH
• Disease Models, Animal MeSH
• Spinal Cord Injuries metabolism   therapy   MeSH
• Swine MeSH
• Mesenchymal Stem Cell Transplantation * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Hydrogels MeSH