Table 2.

Biomaterials used in hydrogels to deliver nonviral vectors.

Nonviral vectors	Materials	Systems	Genes	Release profiles	Efficacy	Targets	References
Naked DNA	PLGA	Injectable implant	luc	Sustained release for 2 months	Sustained expression, tolerance in vivo	CV1 cells, s.c. injection (mouse)	[66]
	pNIPAAm	pNIPAAm-co-AAc nanogel	luc	Not reported	Effective internalization	hMSCs	[67]
			GFP			s.c. injection (mouse)
Lipoplexes	PEG	Hydrogel modified with affinity peptides	luc	~59%, 75%, and 80% in K8, K4, and RGD hydrogels for 6 days	5- to 15-fold increased transfection with K8 and K4 hydrogels	HT1080 cells	[68]
			GFP, luc
	Fibrin	Microspheres in fibrin gel	eNOS	100% release by 24 h from fibrin gels, slower release with microspheres	Enhanced angiogenesis	Ear ulcer model (rabbit)	[69]
Polyplexes	PEG	OPF porous scaffold	SOX trio	Not reported	Combination of RUNX2 and SOX trio DNA improved healing relative to empty hydrogels	Osteochondral defect (rat)	[41]
			RUNX2
			SEAP	Not free diffusion of polyplexes in hydrogel	Reduced polyplexes aggregation, effective gene transfer	NIH 3T3 cells, chorionic chick embryo	[70]
		Hydrogel with nanosized micelles	luc	Not reported	Higher transfection efficiency in the presence of micelles	hMSCs	[71]
	Fibrin		lacZ	<1% released at 3 days	Effective gene transfer	Chorionic chick embryo	[72]
			VEGF
			SEAP	Not free diffusion of polyplexes in hydrogel	Reduced polyplexes aggregation, effective gene transfer	NIH 3T3 cells, chorionic chick embryo	[70]
	HA	Porous HA hydrogel	Gluc	Sustained release for 14 days in the presence of collagenase I treatment (<25% release)	Reduced aggregation of polyplexes	HEK293T cell	[73]
			SEAP
		Fibrin hydrogel	lacZ	<1% released at 3 days	Effective gene transfer	Chorionic chick embryo	[72]
			VEGF
		Microporous HA hydrogel	Gluc	Controlled release for 10 days	Sustained transgene expression for up to 10 days	mMSCs	[74]
		MMP-degradable HA hydrogel	Gluc	Stiffer hydrogels resulted in lower release rates in buffer, collagenase I, and hyaluronidase	Higher N/P ratios lead to higher gene transfer efficiency but also higher toxicity	mMSCs	[75]
			SEAP	Not free diffusion of polyplexes in hydrogel	Reduced polyplexes aggregation, effective gene transfer	NIH 3T3 cells, chorionic chick embryo	[70]

PLGA: poly(lactic/glycolic acid); pNIPAAm-co-AAc: poly(N-isopropylacrylamide-co-acrylic acid); PEG: polyethylene glycol; HA: hyaluronic acid; OPF: oligo(poly(ethylene glycol) fumarate); MMP: matrix metalloproteinase; luc: firefly luciferase; GFP: green fluorescent protein; eNOS: endothelial nitric oxide synthase; SOX: sex determining region Y-box; RUNX2: runt-related transcription factor 2; lacZ: E. coliβ-galactosidase; VEGF: vascular endothelial growth factor; Gluc: Gaussia luciferase; SEAP: secreted embryonic alkaline phosphatase; K8: GCGYGK8 peptide; K4: GCGK4 peptide; RGD: Arg-Gly-Asp; N/P: polyplex nitrogen-to-phosphate ratio; s.c.: subcutaneous; hMSCs: human mesenchymal stem cells; mMSCs: mouse mesenchymal stem cells.