The spinal cord injury (SCI) in most cases is a severe injury of nervous system (DeVivo, 2012; Pretz et al., 2016) with estimated annual global incidence of ~1 million people, and estimated global prevalence of ~27 million people (GBD 2016 …, 2019). The gravest consequence of the SCI is a lifelong loss of motor and other spinal cord functions below the injured region, accompanied with the spasticity syndrome (Holtz et al., 2017), chronic pain (Finnerup et al., 2014) and autonomic imbalance (Hou & Rabchevsky, 2014; Hamid et al., 2018). Its cause represents as injured voluntary efferent spinal neurons innervation, restoring which is a primary task of the SCI treatment. The problem could be solved through development of the tissue neuroengineering transplantation implants, which join polymer matrices and cells of various differentiation degree (Ahuja et al., 2017; Liu et al., 2018; Wang et al., 2018; Liu et al., 2019; Zhang et al., 2019; Shah et al., 2020). The amorphous poly(N-[2-hydroxypropyl]-methacrylamide (PHPMA) hydrogel has long been considered as a prospective matrix (Woerly et al., 1996‒2005; Pertici et al., 2013). Nowadays the synthetic tunnelled matrices are preferred (Koffler et al., 2019), and the SCI laceration models stay the basic ones for most polymer implants effectiveness studies, despite significant autogenic recovery of spinal cord function after partial trans-section (Alizadeh et al., 2019).
The dissertation presents a systemic comparative study of the immediate PHPMA-hydrogel and polyethylene glycol-based tunnelled matrix implantation restorative effect in a spinal lateral hemi-excision in young animals, i.e., under the nervous system higher auto-regeneration (Schwab et al., 1996; Sutherland et al., 2020).
Study design. Male rats (~1 month, ~50 g), inbred derivatives of Wistar line have been used in the study. The study was designed to include 4 experimental groups: Tr╥ — lateral hemisection of the spinal cord on the ~Т12–Т13 (n=11) (n=11); HG╥ — similar SCI with immediate matrix implantation into the injury focus (n=11); Tr□ — spinal lateral hemi-excision ~1 mm on the same level (n=8); HG■ — similar SCI with immediate implantation of the PHPMA-hydrogel fragment (n=6); Tunnel◘ — similar SCI with immediate implantation of the cylinder polyethylene glycol-based synthetic tunnelled matrix, 1 mm in diameter and length, with the tunnel width of 50 µm (n=8).
The following methods were used: estimation of the motor function index (FI) and spasticity index (SI) of the posterior paretic extremity, respectively, by Basso–Beattie–Bresnahan (ВВВ) and Ashworth in our modification. The non-inclusion criteria were: FI of the posterior ipsilateral extremity in 1 week after the trauma >9 ВВВ points and/or FI of the posterior contralateral extremity ≤14 ВВВ point during a long time (totally — 11 animals). The asymptotic deviations of the test dates were allowed during the first 3 weeks, as well as in 8 weeks and 3 months after the injury. Total observation duration — ~5 months. Morphological studies are represented by impregnation of longitudinal spinal cord sections with silver (groups HG■ and Tr□) and nerve tissue basic markers expression immunohistochemical identification (group Tunnel◘). The Mann-Whitney U Test, Wilcoxon Matched Pairs Test, Spearman Rank Order Correlations have been used. Assumptions about the significance of the result were considered true if the probability of realization of the opposite statement was less than 0.05 (p <0.05).
Concluding from the above-mentioned, it should be stated that the immediate implantation of the PHPMA-hydrogel into the laceration SCI focus in young species with the considerable auto-regenerative potential, provides for significant positive effect only with huge spatial spinal cord defect, precisely in the acutest injury stage, which, up to the author’s mind, is related to its immediate antihemorrhagic effect and limitations of secondary alteration responses, despite the axons chaotic growth into the implanted matrix.
Instead, the tunnelled matrix implantation doesn’t affect the acutest injury stage, but significantly changes its further course, increasing the FI values during the first two observation months and nullifying the FI regress during the last two observation months, which is most likely may be related to the axons intergrowth through the matrix tunnels and growth on the matrix external surface.
