Table 3. Hydrogels Containing HA for the Controlled Delivery of Several GFsa.
| system | GF | study | results |
|---|---|---|---|
| alginate/HA hydrogels223 | TGF-β3 | in vitro (MSCs) and in vivo (s.c. implantation in nude mice) | superior chondrogenesis and neocartilage formation compared with controls |
| poly (ε-caprolactone)-collagen/HA hydrogels224 | VEGF and PDGF | in vitro (HUVEC and fibroblasts coculture) | cellular attachment with infiltration and recapitulation of primitive capillary network in the scaffold’s architecture |
| perlecan/heparan sulfate/HA microgels225 | BMP-2 | in vivo (injection in OA model of mice) | treated knees had higher mRNA levels and lesser OA-like damage compared to control knees |
| bisphosphonate-linked HA hydrogel226 | BMP-2 | in vitro (rat osteoblasts or rat MSCs) | bioactive BMP-2 release by enzymatic degradation of the hydrogels |
| HA hydrogels with peptide-binding dendrimers227 | BMP-2 or TGF-β1 | in vitro | significantly lower amounts of growth factors released in the presence of the affinity binding peptide macromolecule |
| photo-cross-linkable HA/platelet rich plasma complexed hydrogel glue228 | PDGF, TGF-β1, and FGF | in vitro (fibroblasts) and in vivo (rabbit cartilage defect model) | increased cell proliferation and migration |
| integrative hyaline-like cartilage formation in vivo | |||
| HA hydrogels reinforced with cellulose nanocrystals and enriched with PLs229 | PDGF and VEGF | in vitro (hDPCs) and in vivo (CAM) | stimulated chemotactic and pro-angiogenic activity by promoting hDPCs recruitment and cell sprouting |
| HA/collagen hydrogels containing high-sulfated HA microgels230 | TGF-β1 | in vitro | increased TGF-β1 retention and retarded release |
| HA/heparin hydrogels231 | BMP-6 | in vitro (myeloma cells or MSCs) | induced osteogenic differentiation and decreased viability of myeloma cell lines |
| HA hydrogel/nanohydroxyapatite particles232 | BMP-2 | in vivo (s.c. implantation in mouse) | addition of hydroxyapatite nanoparticles modified the release pattern of BMP-2, resulting in enhanced bone formation |
| gelatin/HA hydrogel233 | FGF-10 and FGF-7 | in vitro (Calu-3 or MSCs) | epithelial phenotype of MSCs after 2 weeks with reduction of vimentin and increase in pan cytokeratin expression |
a
Abbreviations: BMP-2, bone morphogenetic protein 2; TGF-β3, transforming growth factor beta 3; MSCs, mesenchymal stem cells; s.c., subcutaneous; VEGF, vascular endothelial growth factor; PDGF, platelet-derived growth factor; mRNA, mRNA; HUVEC, human umbilical vein endothelial cells; OA, osteoarthritis; TGF-β1, transforming growth factor beta 1; FGF, fibroblast growth factor; PLs, platelet lysates; hDPCs, human dental pulp cells; CAM, chick chorioallantoic membrane; BMP-6, bone morphogenetic protein 6; FGF-10, fibroblast growth factor 10; FGF-7, fibroblast growth factor 7; FITC, fluorescein isothiocyanate; NT-3, neurotrophin-3; BSA, bovine serum albumin; PLL, polylysine; HEK, human embryonic kidney.