Table 4.

List of various injectable hydrogels having biomedical applications.

Hydrogel	Active Ingredient	Type of Disease	In Vitro Cell Line	In Vivo Model	Conclusion	Reference
Thermosensitive chitosan-based	Disulfiram(DSF)	Cancer	Human HCC cell lines (SMMC-7721 cells)	-	A novel injectable sustained formulation for anticancer drugs aimed at the delivery of DSF for long-term cancer treatment	[61]
Dual thermo-and pH-sensitive injectable hydrogels of chitosan/(poly(N-isopropylacrylamide-co-itaconic acid)	Doxorubicin	Breast cancer	MCF-7 cells	-	Cytocompatible and exert no/negligible cytotoxicity on MCF-7 cells and has the potential for local therapy of breast cancer	[62]
pH-sensitive poly(lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers	Herceptin	Breast cancer	-	SK-BR-3 tumor bearing mice	Great potential for preventing the relapse of HER2+ breast tumors after breast-conserving surgery with ↑ therapeutic efficacy, ↓ side effects and ↑ patient compliance	[63]
pH-sensitive injectable-polysaccharide-based self-healing hydrogels	Doxorubicin	Hepatocellular carcinoma	HepG2(release of drug from hydrogel) L929 cells (Cytotoxicity test of the hydrogel)	-	Self-healing property with high drug-loading ratio could prolong their lifetime during implantation and provide the benefit of nominally invasive surgery	[64]
Dual pH- and temperature-responsive physically crosslinked injectable hydrogel	Cancer	Oncolytic adenoviruses	-	Human xenograft tumor models	Exhibited ↑ and long-term antitumor therapeutic effects in tumor models and might have potential for long-term cancer treatment	[65]
Novel palladium nanosheet (Pd NS)-based chemo-photothermalhydrogel (Pd Gel)	Palladium and doxorubicin	Cancer	-	Mouse	A novel anticancer strategy that allows the release of doxorubicin more precisely, eliminate tumor more efficiently and inhibit tumor metastasis more persistently	[66]
ABA triblock copolymers of vitamin D-functionalized polycarbonate and poly(ethylene glycol), that is, VDm-PEG-VDm were synthesized and employed to form physically crosslinked injectable hydrogels	Bevacizumab; Avastin	Cancer		HCT116 xenograft mouse models	Injection of the hydrogel was effective to show antimetastatic activity as that of 4× weekly injections of Avastin thus ↓ the injection frequency and may ↑ patient compliance to treat metastatic cancer	[67]
pH-responsive injectable hydrogels made of a supramolecular cross-link network	doxorubicin	Cancer	L929 mouse fibroblasts	-	Showed biocompatibility, controlled release profiles and tunable properties which show a ↑ potential as a drug-releasing material for localized treatments	[68]
Triblock Copolymers of Vitamin E-Functionalized Polycarbonate and Poly(ethylene glycol)	Herceptin	Breast cancer	Human breast cancer cell lines (antitumor specificity and efficacy)	BT474 tumor-bearing mice- (biocompatibility and biodegradability)	↑ potential for use in subcutaneous and sustained delivery of antibodies to ↑ therapeutic efficacy and/or ↑ patient compliance as compared to intravenous and subcutaneous delivery of Herceptin in solution form	[69]
pH-responsive injectable hydrogels with mucosal adhesiveness based on chitosan-grafted-dihydrocaffeic acid and oxidized pullulan	Doxorubicin	Colon tumor	Colon tumor cells (HCT116 cells)	-	Showed good drug release, effectively killing colon tumor cells, ideal candidates for development of colon cancer drug delivery carriers /mucoadhesive drug delivery systems	[70]
Alginate hydrogel system	Angiogenesis with vascular endothelial growth factor (VEGF)	Cardiovascular diseases	Human microvascular dermal endothelial cells		Act as a new generation of therapeutic delivery vehicle by combining long-term in vivo therapeutic advantages with minimal invasion to treat cardiovascular diseases	[71]
Dual-responsive (pH and ROS) injectable hydrogels encapsulating drug-loaded micelles	Amikacin, andNaproxen	Wound healing		SD male rats	Possess good biocompatibility with efficient antibacterial and anti-inflammatory action, ↑ the healing process and promising to be applied topically against various microbial infections	[72]
Alginate–chitosan hydrogels	IgG model antibodies and Fab antibody fragments	Applications in drug delivery and regenerative medicine	-	-	Offers controlled delivery of antibodies and antibody fragments and will be promising formulation for several applications in drug delivery and regenerative medicine	[73]
Dopamine-based and polydopamine crosslinked injectable hydrogels	Dopamine and metronidazole	Parkinson’s disease	-	mouse L929 fibroblast cells	Can be used as long-term, localized, sustained release injectable system for dopamine as well as anti-inflammatory drugs to treat Parkinson	[74]
Covalently crosslinked composite hydrogel embedded with microspheres		Soft tissue engineering	-	-	Can be exploited as a potential opportunity to use this injectable composite gel scaffold in protein delivery and soft tissue engineering applications	[75]
Gelatin-hydroxyphenyl propionic acid (Gtn-HPA) and hyaluronic acid-tyramine (HA-Tyr)-based hydrogels	Human epidermal growth factor (hEGF)	Ophthalmic applications			Hydrodynamic model, giving a normalized diffusion and release of hEGF and provide the most suitable explanation for the measured solute diffusion coefficient	[76]
Porous alginate gels	Peptide antigen	Immunotherapies	-	Nonobese diabetic mouse model of type 1 diabetes	A noninflammatory biomaterial system can generate antigen-specific, that may enable the development of new therapies to treat transplant rejection/autoimmune diseases	[77]
Self-healing injectable micelle/hydrogel composites quaternized chitosan (QCS) solution and benzaldehyde-terminated poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO99-b-PPO65-b-PEO99, Pluronic® F127 (PF127)) (PF127-CHO) solution	Curcumin	Wound dressing for joints skin wound healing		Female Kunming mice	Self-healing antibacterial adhesive hydrogels with good mechanical property offer significant promise as dressing materials for joints skin wound healing	[78]
Alginate-gelatin injectable hydrogel	Oligochitosan coated cerium oxide nanoparticles	Age-related macular degeneration	Human retinal pigment epithlium-19 (ARPE-19) and umbilical endothelium	-	Biocompatible and have ↑ potential in protecting cells from angiogenesis, apoptosis, and production of proinflammatory cytokines with controlled drug release	[79]
Decellularized injectable cardiac and skeletal muscle extracellular matrix hydrogel	-	Potential scaffolds for tissue regeneration and/or repair for treating myocardial infarction, heart failure and peripheral artery disease	-	-	Tissue specific biomaterial therapies with minimal invasion	[80]
Polysaccharide-based hydrogels(N-carboxyethyl chitosan and oxidized sodium alginate)	Neural stem cells delivery	Neurological disorders	Neural stem cells	-	Neural stem cells transplantation and management of neurological diseases	[81]
Non-degradable dendritic polyglycerol sulfate (dPGS) hydrogel	Dendritic polyglycerol sulfate	Osteoarthritis	-	-	Formulation having good viscoelastic properties and has the benefit of being much less easily displaced from its injection site	[82]
Conductive anti-oxidant hydrogels (N-carboxyethyl chitosan and oxidized hyaluronic acid-graft-aniline tetramer	Amoxicillin	Wound dressing	C2C12 myoblast cells (Cytocompatibility) Escherichia coli and Staphylococcus aureus (Antibacterial activity)	Male Kunming mice	Have good antibacterial, biodegradation, electroactive and free radical scavenging property to efficiently prevent the wound infection and can be designed as an electroactive injectable hydrogel with promising applications	[83]
Injectable poly(ethylene glycol) (PEG)–gelatin hydrogel	Murine adipose-derived stem cells	Wound Healing and tissue regeneration	-	Murine wound healing model	Significantly ↑ cell retention, ↑ angiogenesis, and ↑ wound closure and can be used for regulating stem cell behaviors in 3D culture, delivering cells for wound healing and other tissue regeneration applications	[84]
Polyplex Micelle-Loaded Injectable Hydrogels	MicroRNA-29	Intervertebral disc degeneration(IDD)		Rabbits (therapeutic efficacy on fibrosis Inhibition) Sprague-Dawley rats (In vivo delivery analysis)	Successfully stop the expression of matrix metalloproteinases, prevent the fibrosis process and reverse IDD in animal models	[85]
Collagen–chitosan-based hydrogel	Thymosin β4, (a 43-amino acid peptide)	Myocardial Infarction	Monolayers of BHK-21		Stimulate angiogenesis and epicardial heart cell migration can be considered as a carrier of other negatively charged active biomolecules and thus shows numerous applications	[86]
Chitosan hydrogel	Human placenta-derived mesenchymal stem cell -derived exosomes	Hindlimb Ischemia	-	Murine model	Can ↑ the retention and stability of exosomes and further ↑ the therapeutic effects that may facilitate the development of easy and effective approaches for assessing and enhancing the therapeutic effects of stem cell-derived exosomes	[87]
Sustained release, thermosensitive polymeric [poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA)]hydrogel	Avastin®	Posterior segment disorders	-	Rat	A promising candidate for ocular drug delivery of Avastin® through intravitreal injection	[88]
Catheter-injectable hydrogel utilizing a polymer–nanoparticle crosslinking mechanism	-	Various therapeutic applications		Wistar rats	Biocompatible, cell-signaling and can be differentially released with distinct elution profiles, allowing precise control over drug delivery	[89]
Self-healing hydrogel based on chondroitin sulfate multiple aldehyde and N-succinyl-chitosan	Cells encapsulated in the hydrogel	Cell carrier and in tissue engineering		Rat model	Shows biodegradability, produced ↓ inflammatory response and having potential application as a cell carrier and in tissue engineering.	[90]
Physiological temperature-responsive controllable NO-releasing redox injectable hydrogel	Nitric oxide(NO)	Cardiovascular diseases	-	Mice	Significantly ↑ the angiogenesis and new blood vessels formation by regulating the sustained release of NO and redox equilibrium in animal model. It has a ↑ potential in preventing and treating diseases	[91]