Abstract
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.
Highlights
Functional deficits of spinal cord injury (SCI) are the result of subsequent temporal events: the primary insult leads to ischemia, followed by neuronal cell death, axon damage, and demyelination
In this study we evaluated two methacrylate hydrogels based on HEMA and HPMA, which are considered to be excellent synthetic biomaterials resembling living tissue, in terms of water content and mechanical properties [28,29]
Our study showed that none of the methacrylate hydrogels caused a significant immune response, as demonstrated by no upregulation of antigen-presenting cells at 3 months
Summary
Functional deficits of spinal cord injury (SCI) are the result of subsequent temporal events: the primary insult leads to ischemia, followed by neuronal cell death, axon damage, and demyelination. The scaffold, suitable for implantation into lesion cavity must have the appropriate chemical, physical, and mechanical properties required for cell survival and tissue formation. One of the most suitable classes of compounds for these purposes is definitely represented by hydrogels [1,2,3] They are three-dimensional (3D) hydrophilic polymers held together by covalent bonds or other cohesive forces such as hydrogen or ionic bonds [3,4,5]. They can be either synthetic or natural in origin, or a combination of both. This is much more difficult to achieve in naturally derived polymers, which, in contrast, have features supporting adhesion and cell growth
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