Table 5.

Engineered exosomes and exosome-loaded drug delivery systems

Category	Biomaterials	Exosomes source	Experimental model	Route of administration	Disease	Biological function	References
Macrophage	Genetically engineered exosomes	M2 macrophages	BALB/c nude male mice	Hypodermic implantation	Diabetic periodontitis	CKIP-1↓, PGC-1α↑	[113]
	Melatonin engineered exosomes	M2 Macrophages	Rat ligature periodontitis model	Injection	Diabetic periodontitis	Reduce excessive endoplasmic reticulum stress and unfolded protein response	[114]
	F127/HA-NB-adhesive dual-sensitive hydrogel	M2 Macrophages	Pentobarbital was used to drill holes in the skulls of SD rat	Fill with the bone defect site	Diabetic bone healing	Promote GSK-3β phosphorylation to activate the wnt signaling pathway and β-catenin signaling pathway	[115]
	PANB/Au/AC-hydrogel	M2 Macrophages	Male C57BL/6J mice were intraperitoneally injected with streptozocin	Bond	Diabetic wound healing	Antibiosis, anti-oxidative stress, anti-inflammatory	[116]
	Double-layer microneedle-based wound dressing system	M2 Macrophages	A female SD rat was intraperitoneally injected with streptozocin	Wound dressing	Diabetic wound healing	Improving the expression of CD31 and VWF to promote angiogenesis	[117]
	Multifunctional hyaluronic acid hydrogel	M2 Macrophages	Bleeding liver of mouse	Stent dressing adhered to the bleeding site	Diabetic foot ulcers	Self-healing and tissue adhesion	[118]
	Ionizable lipid nanoparticles	Peritoneal macrophages	C57BL/6 female mice with a small incision along the midline were made with sterile scissors	Syringe filling	Diabetic wound healing	Promote pancreatic mRNA delivery	[119]
Cells other than macrophages	Engineered exosomes	Adipose stem cells	Male C57BL/6 mice were intraperitoneally injected with streptozotocin and two round full-thickness wounds were made with a skin punch	Subcutaneous injection	Diabetic wound healing	Inhibition of p65 and IκBα phosphorylation	[120]
	Engineered exosomes	Mesenchymal stromal cells (miR-146a)	Male BKS.Cg-m + / + Leprdb/J (db/db) mice	Tail vein injection	Diabetic neuropathy	Activation of vascular endothelial cells and change of axonal sensory transduction characteristics	[121]
	Engineered exosomes	Epidermal stem cells (miR-203a-3p)	Two full-thickness wounds were formed on the back of db/db mice using a punch	Intradermal injection	Diabetic wound healing	Activation of JAK2/STAT3 signaling pathway	[122]
	Engineered exosomes	Bone marrow Mesenchymal stromal cells	Female Wistar rat were intraperitoneally injected with streptozotocin	Intramuscular injection	Diabetic neuropathy	Promote pancreatic cell proliferation and inhibit pancreatic β cell apoptosis	[123]
	All-natural hydrogel	Protocatechuic aldehyde hybridized collagen	Application of streptozotocin to Sprague Dawley rat and creation of a whole wound	Hydrogel treatment	Diabetic wound healing	M1 macrophages are transformed into M2 macrophages	[125]
	Graphene oxide-loaded gelatin-alginate hydrogel	Platelet cells	Establishment of chronic full-thickness dorsal skin wounds in diabetic Wistar rat	Local application	Diabetic wound healing	Promote HSP expression and M2 macrophage polarization	[126]
	Injectable hydrogel	Human adipose-derived mesenchymal stem cells	Establishment of round full-thickness wounds in male SD rat diabetic model	Tegaderm film coverage	Diabetic wound healing	Promote M2 macrophage polarization	[127]
	Bioinspired adaptable indwelling microneedle	Mesenchymal stem cells	Diabetic rat model to create a circular full-thickness wound	Skin penetration	Diabetic Ulcers	Inhibit M1 macrophage polarization	[128]
	Electroconductive nerve dressing	Bone marrow stem cells	A diabetic sciatic nerve crush injury model was established in female SD rat	No.25 needle injection	Diabetic neuropathy	Through NF-κB pathway regulates macrophage polarization	[129]