Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair

Table 1

Biomaterials used in hydrogels to deliver growth factors.

Hydrogels	Growth factors	Systems	Targets	Incorporation	Release profile	References
Alginate	VEGF, PDGF-BB, TGF-β1		MSCs	Affinity interaction	Sequential release	[19]
	TGF-β3, BMP-2	Peptide-modified alginate	MSCs		Dual release	[18]
Fibrin	IGF-I	Clot	Chondrocytes/cartilage defect (horse)	Encapsulation	n.a.	[25, 27]
	TGF-β1	Fresh and platelet-rich plasma fibrin	MSCs	Immobilization with heparin	n.a.	[28]
	TGF-β1		MSCs	Encapsulation	Decreased release with higher fibrinogen component	[26]
	TGF-β1		n.a.	Conjugation	Sustained release	[30]
Hyaluronan	TGF-β1	HA hydrogel with alginate microspheres	MSCs	Loading in microspheres	Reduced burst effect and sustained release for 6 days	[24]
	BMP-2	Heparin-decorated HA hydrogel particles	MSCs	Immobilization with heparin	Zero-order release kinetics	[23]
Chitosan	TGF-β1	Chitosan/collagen	MSCs	Conjugation	Sustained release with minimal burst effect	[60]
PEG	IGF-I, BMP-2	OPF	Osteochondral defect (rabbit)	Loading in gelatin microparticles	n.a.	[42]
	IGF-I, TGF-β1				High TGF-β1 and low IGF-I burst release followed by controlled release for 28 days	[40]
	TGF-β1	OPF	Bovine chondrocytes	Loading in gelatin microparticles	Controlled release for 28 days	[39]
	TGF-β1	PEG-genipin hydrogel with PLGA microspheres		Loading in PLGA microspheres	Sustained release for 21 days and minor burst with microspheres embedded in hydrogels	[33]
	IGF-I, TGF-β1	Photopolymerized hydrogel	Chondrocytes	Loading in PLGA microspheres	Controlled release for 2 weeks	[38]
Self-assembling peptides	TGF-β1	KLD12	MSCs	Tether or adsorption	50% released after 21 days	[35]
	TGF-β1	(RADA)4, (KLDL)3	MSCs	Tether or adsorption	Effective release by absorption	[36]
pNIPAAm	TGF-β3	pNIPAAm-coAAc	MSCs	Entrapment	Initial burst and zero-order release profile after 7 days	[43]
PVA	IGF-I	PLGA microparticles in PVA hydrogels	s.c. implantation (athymic mouse)		Controlled release for 6 weeks	[34]

PEG: polyethylene glycol; pNIPAAm: poly(N-isopropylacrylamide); PVA: poly(vinyl alcohol); VEGF: vascular endothelial growth factor; PDGF-BB: platelet-derived growth factor BB; TGF-β: transforming growth factor beta; BMP: bone morphogenetic protein; IGF-I: insulin-like growth factor I; HA: hyaluronic acid; OPF: oligo(poly(ethylene glycol) fumarate); PLGA: poly(lactic/glycolic acid); KLD₁₂: self-assembling peptide with AcN-(KLDL)₃-CNH₂ sequence; RADA: self-assembling peptide with RAD motif; KLDL: self-assembling peptide with KLD sequence; MSCs: mesenchymal stem cells; n.a.: not applicable; s.c.: subcutaneous.