Table 3:

Hybrid hydrogels and their reported biomedical applications

Hybrid hydrogel components	Nano/microstructure incorporation strategy	Nano/microstructure or drug release mechanism	Targeted disease	Potential outcome	Reference
Sodium alginate/PLGA microspheres loaded with HSP27 (heat shock protein 27) fused to TAT peptide	Physical incorporation of microspheres followed by alginate crosslinking with calcium sulfate	Pore size regulated HSP27 release from microspheres	Myocardial infarction	Suppression of apoptosis and improved ejection fraction, end-systolic volume and maximum pressure developement in the heart	[75]
Sodium alginate/3D Ormocomp scaffold	Sodium alginate solution along with human adipose-derived stem cells (ASCs) were added to 3D scaffold and crosslinked using ionic cross-linking or RGD based crosslinking method	The gel containing scaffolds are stable for eight weeks and ASCs produced dopamine	Parkinson’s disease	Prevention of immune rejection of the non-autologous cells by the extremely small pore size of the alginate gel; higher dopamine secretion by hybrid hydrogel was evident as compared to conventional alginate hydrogel	[76]
PECA [poly(ε-caprolactone)-acryloyl chloride]/COS-GMA (glycidylmethacrylated chitooligosachharide)/NIPAm (N-isopropylacrylamide)/AAm (acrylamide)/Gold nanorods (GNR)/doxorubicin	Physical encapsulation of GNRs and doxorubicin in hydrogels developed by heat-initiated free radical polymerization using ammonium persulfate as a heat initiator	Temperature and pH dependent doxorubicin release profile; NIR laser irradiation of GNRs increased the temperature and thus improved doxorubicin release	Breast cancer	Significantly reduced postoperative tumor recurrence in in vivo mouse model	[74]
Acrylamide/RBC membrane coated PLGA nanoparticles (nanosponges)	Physical encapsulation of nanosponges before gelation	Pore forming α-toxin absorption by nanosponges	Methicillin resistant Staphyloco ccus aureus (MRSA) infection	Effective detoxification with marked reduction in MRSA skin lesion development in mouse models	[77]
Quaternized chitosan (HTCC)/silver nanoparticles/graphene oxide (GO)/voriconazole	Physical encapsulation of silver nanoparticles and GO in HTCC solution; electrostatic interactions between GO and HTCC resulted in hydrogel crosslinking	Voriconazole is loaded onto GO by Π-Π stacking interactions and released slowly	Fungal keratitis	Enhanced antibacterial properties in vitro and anti-fungal properties in vivo in fungal keratitis mouse model	[79]
Rapamycin-loaded unimolecular micelles/PLGA-PEG-PLGA	Physical dispersion in triblock gel	Diffusion of rapamycin from the unilamellar micelle dispersed triblock gel	Prevention of neointima-caused re(stenosis) after open surgery such as bypass surgery	Sustained rapamycin release for four months; inhibition of re(stenosis) by 80% even after three months as compared to no drug treatment	[88]
Carboxymethyl chitosan (CC)/Aldehyde hyaluronic acid (AHA)/VEGF loaded porous PLGA micro sphere/vancom ycin	Physical encapsulation of VEGF loaded porous PLGA microspheres in CC/AHA hydrogel	Vancomycin linked to injectable hydrogel via the reversible Schiffs base reaction is released by change in the pH from netural to acidic in infected wounds; VEGF release was dependent on the pore size of PLGA microspheres	Non-healing infected wounds	Inhibited bacterial growth; accelerated vein endothelial cell proliferation with reduced inflammation; promoted angiogenesis.	[78]
Chondriotin sulfate (CS) and poly(ethylene glycol) (PEG)	FXIIIa-mediated crosslinking of CS-Mal grafted with MMP-Lys and PEG-Gln	The degree of CS grafting with MMP-Lys and stoichiometry of the hydrogel components dictated hydrogel properties, and the gel was degradable by chondriotinase and MMP to promote cell proliferation, migration, and viability.	Osteogenesis	Tuned growth factor binding and release; generated a cell instructive matrix; promoted stem cell proliferation and osteogenic differentiation.	[73]