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

0493200 - ÚEM 2019 RIV US eng J - Článek v odborném periodiku
Závišková, Kristýna - Tukmachev, Dmitry - Dubišová, Jana - Vacková, Irena - Hejčl, Aleš - Bystronová, J. - Pravda, M. - Scigalková, I. - Šuláková, R. - Velebný, V. - Wolfová, Lucie - Kubinová, Šárka
Injectable hydroxyphenyl derivative of hyaluronic acid hydrogel modified with RGD as scaffold for spinal cord injury repair.
Journal of Biomedical Materials Research. Part A. Roč. 106, č. 4 (2018), s. 1129-1140. ISSN 1549-3296. E-ISSN 1552-4965
Grant CEP: GA ČR(CZ) GA15-01396S; GA MŠMT(CZ) LO1309; GA MŠMT(CZ) EF15_003/0000419
Institucionální podpora: RVO:68378041
Klíčová slova: hyaluronic acid * spinal cord injury * scaffold * mesenchymal stem cells * regenerative medicine
Obor OECD: Biomaterials (as related to medical implants, devices, sensors)
Impakt faktor: 3.221, rok: 2018

Hydrogel scaffolds which bridge the lesion, together with stem cell therapy represent a promising approach for spinal cord injury SCI repair. In this study, a hydroxyphenyl derivative of hyaluronic acid HA-PH was modified with the integrin-binding peptide arginine-glycine-aspartic acid RGD, and enzymatically crosslinked to obtain a soft injectable hydrogel. Moreover, addition of fibrinogen was used to enhance proliferation of human Wharton's jelly-derived mesenchymal stem cells hWJ-MSCs on HA-PH-RGD hydrogel. The neuroregenerative potential of HA-PH-RGD hydrogel was evaluated in vivo in acute and subacute models of SCI. Both HA-PH-RGD hydrogel injection and implantation into the acute spinal cord hemisection cavity resulted in the same axonal and blood vessel density in the lesion area after 2 and 8 weeks. HA-PH-RGD hydrogel alone or combined with fibrinogen HA-PH-RGD/F and seeded with hWJ-MSCs was then injected into subacute SCI and evaluated after 8 weeks using behavioural, histological and gene expression analysis. A subacute injection of both HA-PH-RGD and HA-PH-RGD/F hydrogels similarly promoted axonal ingrowth into the lesion and this effect was further enhanced when the HA-PH-RGD/F was combined with hWJ-MSCs. On the other hand, no effect was found on locomotor recovery or the blood vessel ingrowth and density of glial scar around the lesion. In conclusion, we have developed and characterized injectable HA-PH-RGD based hydrogel, which represents a suitable material for further combinatorial therapies in neural tissue engineering.
Trvalý link: http://hdl.handle.net/11104/0286609