Table 3.

Hydrogel and hydrogel nanocomposites for treating diseases resulting from chronic exposure to environmental contaminants.

	Hydrogel/hydrogel nanocomposite	Drug	Application	Key results	Reference
Cancer	ERT MS-embedded HP9/HD cross-linked hydrogel (Erlotnib microsphere-embedded hyaluronic acid-phenylboronic acid/dopamine hydrogel)	Erlotinib (ERT)	Peritumoral injection of an anticancer agent for local cancer therapy	Sustained locoregional delivery of ERT, enhanced cancer curing efficiencies, sustained local delivery, short gelation time, single syringe injection, self-healing potential, high retention time	[180]
	Visible light-cured glycol chitosan (GC) hydrogel containing paclitaxel (PTX)-complexed beta-cyclodextrin(-CD) (GC/CD/PTX)	Paclitaxel (PTX)	Injectable drug delivery depot system for ovarian cancer	Sustained and controlled release of PTX, single local administration showed antitumor efffect for 7 days in mice	[181]
	Self-assembled dextran sulfate (DS)-DOX complexes encapsulated in agarose hydrogel	Doxorubicin (DOX)	Local injected into the cavity after lumpectomy for sustained delivery of low dose DOX	Completely elimination of MDA-MB-231 breast cancer cells with low cytotoxicity to NIH 3T3 fibroblasts	[182]
	CREKA-conjugated dextran-coated iron oxide nanoparticles	Cisplatin	Systemic tumor targeting to treat lung cancer	Enhanced permeation and stability retention in cell culture, effective at targeting fibrinogen overexpressed in tumor tissues, nontoxic over long period of time, synergistic effect of cisplatin and hyperthermia	[194]
	Hyaluronic acid (HA) hydrogel covalently embedded with doxorubicin loaded and triphenylphosphine (TPP) core–shell gold mesoporous silica nanoparticles	Doxorubicin (DOX) and triphenylphosphine (TPP)	Local drug-delivery system for sustained stomach cancer treatment	Development of as an implantable drug-delivery system for local synergistic chemophotothermal cancer therapy	[195]
Diabetes	4-Carboxy-3-fluorophenylboronic acid (FPBA) modified with biodegradable poly(l-lysine) (PLL) polymers for constructing polymer−insulin complexes	Insulin	Glucose-stimulated insulin delivery	Construction of polymer–insulin complexes, blood glucose regulation ability, glucose-triggered insulin release in type 1 diabetic mice	[212]
	Silk fibroin hydrogel (iSFH)	Insulin	Subcutanoues injectable hydrogel for sustained insulin delivery	Insulin–iSFH in diabetic rats forms active depot under skin for slow sustained release of insulin and restoration glucose homeostasis for 4 days, insulin–iSFH did not cause hypoglycemia	[213]
	Oligomer serine-b-poly(lactide)-b-poly(ethyleneglycol)-bpoly(lactide)-b-oligomer serine (OS-PLA-PEG-PLA-OS) pentablock copolymer, as matrix and chitosan–insulin electrosprayed nanospheres (CIN) as constituent materials	Insulin	In situ injectable pH-temperature sensive hydrogel system—biodegradable after 5 weeks	Steady state insulin delivery into induced diabetic mice with no changes in plasma concentrations, blodd glucose level reduction effects for over 60 h	[214]
	Polyacrylamide bidentate ß-cyclodextrin-based hydrogel with preloaded insulin	Insulin	Injectable biomimetic glucose trigger-insulin release system	Dual self-regulated system shows a specific d-glucose response to realize accurate monitoring and simultaneous on-demand trigger insulin release, enables long lasting blood glucose control	[215]
	pH-sensitive semi-interpenetrating polymer network (IPN) hydrogel	Insulin	Oral insulin delivery	In vitro insulin release is pH dependent, blood glucose level reduction with oral administration of insulin-loaded hydrogel in mice studies	[226]
Cardiovascular disease	Controllable NO-releasing redox injectable hydrogel (NO-RIG) composed of dual bifunctional triblock copolymers	NO	Injectable hydrogel system	Scavenges overproduced ROS and regulates local NO expression level simultaneously, exhibited therapeutic efficiency without any conventional drugs or biomolecules	[244]
	Mixed component hydrogel capable of releasing both bioactive curcumin and NO	Curcumin and NO	Injectable hydrogel for myocardial infraction (MI)	Combinational treatment of curcumin and NO reduces collagen deposition, improves cardiac function, ameliorates adverse myocardium remodeling, suppresses apoptosis, and hypertrophy (synergistic effect)	[247]
	GST-TIMP-bFGF/collagen-GSH hydrogels	Recombinant protein GST-TIMP-bFGF (basic fibroblast growth factor)	Dual function, MI-responsive on-demand growth factory delivery system	Promotes recovery of MI rats by enhancing vascularization and ameliorating myocardium remodeling in in vitro and in vivo studies	[252]
	Tissue-derived extracellular matrix (ECM)/silk fibroin (SF) composite scaffolds with Au nanoparticles and mesenchymal stem cells (MSCs)	–	Cardiac patch for infarcted myocardium regeneration	Formation of well-interconnected porous surface ECM cardiac composite patches with Au and SF proteins improves cell proliferation and migration with suitable physiological properties. Au–ECM/SF patches made suitable atmosphere for cell growth at higher number and adhered cardiomyocytes with homogeneous spreading on the patches	[256]
	Polyvinylalcohol/dextran (PVA/Dex) elastic hydrogel patches	Astaxanthin	Cardiac patch to assist responses against myofibril stress	Elastic hydrogel materials can load astaxanthin without affecting antioxidant properties, sustained antioxidant release, patches can be implanted in rats without damage to surrounding tissue	[257]
Alzheimer’s disease	liposomal donepezil HCl (LDH) dispersed into thiolated chitosan hydrogel (TCH)	Donepezil HCl (DH)	Intranasal delivery	In vivo rabbits’ studies showed LDH incorporated into TCH significantly increasing the blood and brain of DH compared to the oral tablets	[267]
	Mixture of two hydrophilic polymers (Poloxamer 407 and Poloxamer 188)	Active pharmaceutical ingredient (API)	Controlled intranasal delivery of an active pharmaceutical ingredient (API) via liposomes	Good natural mucoadhesive characteristics of in situ gel formulations which increased when liposomes were added, controlled API release, decreased systemic exposure with increased bioavialbility in the CNS	[268]
	Dual temperature/ion-sensitive in situ hydrogel (ISG)	Timosaponin BII	Intranasal delivery	Brain-targeted drug delivery signaling good Alzheimer’s prevention	[269]
Chronic respiratory disease	Poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in a poly(N-isopropylacrylamide) (p-NIPAAm)-based hydrogel	Mometasone furoate	Thermogel, Extended-release Microsphere-based-delivery to the Paranasal Sinuses (TEMPS) for reduction of sinonasal inflammation	System undergoes reversible sol–gel transition at 34–35 °C applied as a liquid at ambient temperature and conforming to the sinonasal epithelium as it gels, TEMPS was maintained in rabbit sinuses and effectively reduced sinonasal inflammation, thermogel matrix is non-biodegradable but the system is temporary and can be readily removed and reapplied as needed	[281]
	Hyaluronan and heparin-based hydrogel system with encapsulated IL-10	IL-10	Intranasal delivery for idiopathic pulmonary fibrosis (IPF) in the lung	Hhydrogel delivery system for IL-10 attenuates lung fibrosis due to inhibition of TGFβ−1 activation of fibroblasts in an animal model of IPF, intranasal administration effectively delivers sufficient hydrogel deposition to small airways and lung parenchyma	[282]
	Hydrogel scaffold based on natural polymers gelatin and alginate	–	Catheter-injectable gelatin–alginate hydrogel	Hydrogel scaffold can be injected through long catheters, exhibiting physical and mechanical properties necessary for dual treatment of remodeling the lung architecture as a lung volume reduction material and developing a platform for tissue regeneration to allow for cell or organoid implant	[283]