Adhesive hydrogels in osteoarthritis: from design to application

Table 1 Functional components for biological functions

Functional components	Function	Molecular pathways	Pre/clinic state	References
HA	Anti-inflammation; Pain relief	Combined with TLR-2 and TLR-4→TNF-α, IL-1β, IL-17, MMP-13, iNOS↓	Humans, mice, rats	[150,151,152]
	Chondrogenesis; Inhibition of degradation; Adaptation to mechanical stress	Combined with ICAM-1→NF-κB↓→IL-6↓ Combined with CD44→PGE2↓, HSP70↑	Guinea pigs, rabbits, mice	[151]
	Promotion of angiogenesis	Combined with CD44→IL-1β↓→MMP 1,2,3,9,13↓	Rabbits, rats, mice	[152,153,154]
	Improvement of cell proliferation	N/A	Mice	[150,151,152, 154, 155]
Gelatin	Cell proliferation	N/A	Mice	[155, 156]
Alginate	Adaptation to mechanical stress	N/A	Mice	[96, 97]
Alginate	Improvement of cell proliferation	N/A	Mice, horses	[97, 157]
CS	Anti-inflammation; Pain relief; Cell proliferation	p38 MAPK, Erk1/2↓	Rats, humans, rabbits	[158,159,160,161,162]

CD44 cluster determinant 44, CS chondroitin sulfate, Erk1/2 extracellular signal-regulated kinase 1/2, HA hyaluronic acid, HSP70 heat shock protein 70, ICAM-1 intercellular adhesion molecule-1, IL interleukin, NF-κB nuclear factor kappa-B, iNOS inducible Nitric oxide synthase, MMP matrix metalloproteinase, p38 MAPK p38 mitogen-activated protein kinase, PGE2 prostaglandin E2, TLR toll-like receptor, TNF-α tumor necrosis factor α, N/A not applicable

ISSN: 2054-9369