. Author manuscript; available in PMC: 2016 Apr 1.

Published in final edited form as: Adv Drug Deliv Rev. 2014 Jun 30;84:123–134. doi: 10.1016/j.addr.2014.06.006

Table 1.

Biologics delivered for in vitro and in vivo cartilage repair applications

Biologics	Biological Effect	Biologic Type	In vitro/In vivo Model	Comments	References
PTHrP	Anti-Hypertrophy	Growth Factor	In vitro cultures; In vivo OC defect model	Inhibited hypertrophy of chondrocytes and MSCs during differentiation in vitro; Reduced, but did not prevent, calcification in vivo	[137]
S-(+)-ibuprofen	Anti-inflammatory	Small Molecule	Ex vivo OA model	Reduced prostaglandins synthesis at 50 μM. When released from PLGA-PEG microspheres, reduced cartilage degradation at 1 mM ex vivo	[82, 142]
Sulforaphane	Anti-inflammatory	Small Molecule	In vitro cultures; In vivo OA model	Inhibited inflammatory markers including COX-2, ADAMTS-5, and MMP-2 in vitro; Delayed progression of OA in vivo	[86]
IL-1Ra	Anti-inflammatory	Antigen	In vitro cultures; In vivo OA model	Bound to IL-1 surface receptors of synoviocytes in vitro; Retained in joint without inducing degenerative changes in vivo; Specific chondroprotective effects need to be evaluated	[108]
3,4,6-O-Bu3GlcNAc	Anti-inflammatory/Chondroprotective	Small Molecule	In vitro cultures	Decreased the expression of IL-1β-stimulated NFkB target genes and increased GAG production and chondrogenic gene expression of IL-1β challenged chondrocytes	[173]
SDF-1	Cell Homing	Chemokine	In vitro cultures; In vivo OC model and intraperitoneal cell migration model	Did not influence proliferation/chondrogenesis of MSCs in OC defect but resulted in ectopic cartilage formation when delivered with TGF-β1 at 4 weeks in vivo	[61, 174]
PRP	Chondrogenic/Anabolic/Anti-inflammatory	Growth Factor Cocktail	In vitro and ex vivo cultures; In vivo OA and OC defect models	Decreased the expression of inflammatory markers including TNF-α and MMP-13 and enhanced endogenous HA production ex vivo; OC graft pre-treatment with PRP enhanced graft-host integration in vivo	[157, 162]
HA	Chondroprotective	Viscosupplement	In vitro cultures; In vivo OA models	High molecular weight HA resulted in improved histological scores and lower cartilage friction coefficients when compared to low molecular weight HA in vivo	[71]
Proteoglycan 4	Chondroprotective	Viscosupplement	In vitro cultures	Supplementation of OA synovial fluid with proteoglycan 4 restored lubricating ability by reducing friction coefficient in cartilage-on-cartilage tests	[175]
Prostaglandins E2	Inflammatory/Anabolic	Small Molecule	In vitro cultures	Low concentrations (10⁻⁹ M to 10⁻⁶ M) stimulated increased chondrogenic gene expression of articular chondrocytes in 3D	[83]