The loss of neurons and degeneration of axons after spinal cord injury result in the loss of sensory and motor functions. A bridging biomaterial construct that allows the axons to grow through has been investigated for the repair of injured spinal cord. Due to the hostility of the microenvironment in the lesion, multiple conditions need to be fulfilled to achieve improved functional recovery. A scaffold has been applied to bridge the gap of the lesion as contact guidance for axonal growth and to act as a vehicle to deliver stem cells in order to modify the microenvironment. Stem cells may improve functional recovery of the injured spinal cord by providing trophic support or directly replacing neurons and their support cells. Neural stem cells and mesenchymal stem cells have been seeded into biomaterial scaffolds and investigated for spinal cord regeneration. Both natural and synthetic biomaterials have increased stem cell survival in vivo by providing the cells with a controlled microenvironment in which cell growth and differentiation are facilitated. This optimal multi‒disciplinary approach of combining biomaterials, stem cells, and biomolecules offers a promising treatment for the injured spinal cord.

Though recent studies advance the body of knowledge needed to treat degenerated discs, many challenges need to be overcome before the application of these approaches can be successful clinically.

The therapeutic potential of human mesenchymal stromal cells (h‐MSC) is dependent on the viability and secretory capacity of cells both modulated by the culture environment. Our previous studies introduced heparin and collagen I (HEP/COL) alternating stacked layers as a potential substrate to enhance the secretion of immunosuppressive factors of h‐MSCs. Herein, we examined the impact of HEP/COL multilayers on the growth, morphology, and secretome of bone marrow and adipose‐derived h‐MSCs. The physicochemical properties and stability of the HEP/COL coatings were confirmed at 0 and 30 days. Cell growth was examined using cell culture media supplemented with 2 and 10% serum for 5 days. Results showed that HEP/COL multilayers supported h‐MSC growth in 2% serum at levels equivalent to 10% serum. COL and HEP as single component coatings had limited impact on cell growth. Senescent studies performed over three sequential passages showed that HEP/COL multilayers did not impair the replicative capacity of h‐MSCs. Examination of 27 cytokines showed significant enhancements in eight factors, including intracellular indoleamine 2, 3‐dioxygenase, on HEP/COL multilayers when stimulated with interferon‐gamma (IFN‐γ). Image‐based analysis of cell micrographs showed that serum influences h‐MSC morphology; however, HEP‐ended multilayers generated distinct morphological changes in response to IFN‐γ, suggesting an optical detectable assessment of h‐MSCs immunosuppressive potency. This study supports HEP/COL multilayers as a culture substrate for undifferentiated h‐MSCs cultured in reduced serum conditions.

Degeneration of intervertebral discs (IVDs) results in an overall alteration of the biomechanics of the spinal column and becomes a major cause of low back pain. In this study, an injectable hydrogel composite is fabricated and characterized as a potential scaffold for the treatment of degenerated IVDs. Crosslinking of type II collagen-hyaluronic acid (HA) hydrogel with 1-ethyl-3 (3-dimethyl aminopropyl) carbodiimide (EDC) increases the gel stability against collagenase digestion and reduces water uptake in comparison with non-crosslinked gel. Cell viability assay exhibits the proliferation of human nucleus pulposus (HNP) cells in hydrogels. The cells in non-crosslinked gel and the gel crosslinked with a low concentration of EDC (0.1 mM) show superior cell viability and morphology compared with cells in gels crosslinked with higher concentration of EDC. Quantitative PCR assay demonstrates the gene expression of extracellular matrix (ECM) by cells cultured in the gels. The expression of ECM genes by HNP cells in the gels demonstrated the phenotypic change of the cells. This study suggests that the type II collagen-HA hydrogel and crosslinked hydrogel (0.1 mM EDC) are permissive matrix for the growth of HNP cells and can be potentially applied in NP repair.

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