Peptide-Tethered Hydrogel Scaffold Promotes Recovery from Spinal Cord Transection via Synergism with Mesenchymal Stem Cells

Abstract

Spinal cord injury (SCI) is one of the most devastating injuries. Treatment strategies for SCI are required to overcome comprehensive issues. Implantation of biomaterial scaffolds and stem cells has been demonstrated to be a promising strategy. However, a comprehensive recovery effect is difficult to achieve. In the comprehensive treatment process, the specific roles of the implanted scaffolds and of stem cells in combined strategy are usually neglected. In this study, a peptide-modified scaffold is developed based on hyaluronic acid and an adhesive peptide PPFLMLLKGSTR. Synchrotron radiation micro computed tomography measurement provides insights to the three-dimensional inner topographical property and perspective porous structure of the scaffold. The modified scaffold significantly improves cellular survival and adhesive growth of mesenchymal stem cells during 3D culture in vitro. After implantation in transected spinal cord, the modified scaffold and mesenchymal stems are found to function in synergy to restore injured spinal cord tissue, with respective strengths. Hindlimb motor function scores exhibit the most significant impact of the composite implant at 2 weeks post injury, which is the time secondary injury factors begin to take hold. Investigation on the secondary injury factors including inflammatory response and astrocyte overactivity at 10 days post injury reveals the possible underlying reason. Implants of the scaffold, cells, and especially the combination of both elicit inhibitory effects on these adverse factors. The study develops a promising implant for spinal cord tissue engineering and reveals the roles of the scaffold and stem cells. More importantly, the results provide the first understanding of the bioactive peptide PPFLMLLKGSTR concerning its functions on mesenchymal stem cells and spinal cord tissue restoration.

Harnessing the Properties of Biomaterial to Enhance the Immunomodulation of Mesenchymal Stem Cells

“…35 In another study using the same SCI model, HA hydrogel-encapsulated MSCs reduced the percentage of CD68 + M1 macrophages compared to free MSCs. 36 The phenotype of MSCs also varies between 3D and 2D culture. Compared to 2D cultures, a lower percentage of MSCs that expanded in 3D scaffold expressed CD90, CD105,…”

“…In vivo implantation into rat SCI model Encapsulated MSCs resulted in enhanced level of antiinflammatory M2 macrophages. 36 HA hydrogel encapsulation vs. free cells…”

“…35 Some biomaterials, such as HAs, suppress inflammation, 40 and so cell-free biomaterial must be used as a control. 36 During 3D cultivation, cells may regain their in vivo immunophenotype and function. Although MSCs in 3D culture have a greater stemness and differentiation capacity than those on 2D plastic plates, adipose-derived MSCs cultured in 3D alginate scaffold exhibited a drastically different gene expression profile than those freshly isolated from fat tissue, 8 suggesting that dimensionality affects the fate and function of MSCs in vitro differently from in vivo.…”

Injectable hydroxyphenyl derivative of hyaluronic acid hydrogel modified with RGD as scaffold for spinal cord injury repair

“…In neural tissue engineering, HA‐based materials have been studied in vitro as substrates for neural stem cell cultures, as well as in vivo , alone or as carriers for cell delivery to improve cell retention and integration . Injectable HA‐based hydrogels were also developed for localized intrathecal delivery of bioactive molecules into the SCI …”

“…Correspondence to: S. Kubinova; e-mail: sarka.k@biomed.cas.cz to improve cell retention and integration. 10,20,21 Injectable HA-based hydrogels were also developed for localized intrathecal delivery of bioactive molecules into the SCI. 22,23 Native HA does not form a gel nor support cell adhesion.…”