Hydrogel-Loaded Exosomes: A Promising Therapeutic Strategy for Musculoskeletal Disorders

Table 2

Comparison of advantages and disadvantages of various biological scaffold materials.

Material types	Further classification	Rohstoffe	Ingredients	Advantages	Disadvantages	References
Hydrogel scaffold	Natural hydrogels	Alginate salt	Linear polysaccharide copolymer	Low cost can be made from algae and bacteria; low biological toxicity; low immunogenicity	Part of the molecular chain dissociates during the gelation process; low mechanical stiffness; weak cell-matrix interactions resulting in poor cell adhesion	[117–119]
		Chondroitin sulfate	N-Acetylgalactosamine and glucose	Good for restoring stiffness to damaged cartilage; pro-proliferative; low cytotoxicity	Insufficient mechanical strength; degrades too quickly; and needs to be used in combination with other materials	[120]
			Glucuronide chain polymer
		Hyaluronic acid (HA)	Glycosaminoglycan	An important component of the ECM and can simulate the microenvironment of cell survival	Natural HA molecules have poor cell adhesion in organisms and are easily degraded and diffused; too rapid a degradation rate will result in insufficient residence time in the body	[121–125]
				Immunogenicity is extremely low
				Strong stability
				Easy to modify in order to meet a variety of application scenarios
		Chitosan	Linear polysaccharide	Easily modified for a variety of applications; chemically modifiable; antibacterial properties; easy to manufacture; some pain relief	Poor self-mechanical properties; sensitive to pH and temperature; low cell adhesion	[126, 127]
		Gelatin	Triple helix broken collagen	Good water solubility	Poor thermal stability; blocky degradation rate; poor mechanical properties	[127, 128]
				Numerous RGD peptide sequences can enhance cell attachment
				Excellent physical properties
				Easy to modify
		Fibrous protein	Polypeptide chain	Very low antigenicity	Requires modification; the original structure aperture is too small; Low stiffness	[129–131]
				Can be made from blood
				Easy to prepare directional structures
		Collagen	Collagen	Low antigenicity; low inflammatory response; degradable; high biocompatibility	Potential immunogenic risk; insufficient mechanical properties; excessive degradation rate	[132]
		Silk fibroin	Multilayer protein polymer	Long degradation time; can provide long-term support for tissue; nontoxic in the body; excellent physical performance	Slow gelation rate; insufficient inductivity of seed cells; difficulty binding to surrounding tissue	[133, 134]
		GelMA	Gelatin derivative	Can form a three-dimensional structure similar to normal tissue	Curing conditions require high requirements, light intensity, light distance, and light time need to be strictly controlled	[13, 135–138]
				Excellent biocompatibility
				Fast crosslinking
				The physical and chemical properties are flexible and adjustable
	Synthetic hydrogels	PHEMA	The polymer of vinyl	Adjustable mechanical properties, suitable for different parts of the tissue	Different from the natural tissue structure	[139]
		PVA		Excellent elasticity and material endurance	Interaction with cells is poor; oligopeptide coupling modification is required	[140]
				Can be used to repair cartilage tissue
		PEG	Glycol polymer	Responsiveness of stimulus; controlled degradation time	It is different from the natural tissue structure	[141, 142]
	Mixed hydrogels	GelMA-dHAMMA	Mixed material	Porous structure with two-component polymer network; promotes skin healing; can stably simulate the extracellular micro-environment; convenient and fast preparation	The degree of crosslinking is higher than GelMA, and the water absorption becomes weaker	[143]
Metal biological scaffold	Non-degradable metal	Titanium/titanium alloy	Ti, Ti6Al4V	High mechanical strength; low density; nontoxic; high biocompatibility; corrosion resistance	Lack of biodegradability; microstructure has a great influence on mechanical properties	[144]
	Degradable metal	Magnesium, iron, and their alloys	Metal/alloy/coated metal	High mechanical strength; degradable; and the degradation product is nontoxic; metal ions promote tissue healing, especially bone healing	The degradation speed is too fast, which requires coating modification. The degradation rate is difficult to control, and mechanical properties will be affected along with degradation	[96, 145]
		Zinc (zinc oxide)	Metal/metal oxide	Antibacterial ability; good biocompatibility; good osteogenic effect	Need 3D printing technology support; high preparation difficulty	[146]
Bioceramic scaffolds	Bioceramics	Hydroxyapatite, tricalcium phosphate, biphase calcium phosphate, etc.	Hydroxyapatite is the main inorganic substance	Good biocompatibility and bioactivity; wide source, low cost; easy synthesis and preparation	Slow degradation rate; poor mechanical properties	[147, 148]
	Composite biological ceramics	Bioceramics combine metal and polymer materials	Composite material	The mechanical properties of composite bioceramic scaffolds were improved by integrating the advantages of other materials	The preparation is complex and needs to consider the organizational environment and other factors	[149]
	Biodegradable bioceramics	Calcium sulfate, tricalcium phosphate, etc.	Calcium compound	Degradation products such as Ca and P do not produce rejection reaction; good biocompatibility; good bone induction ability	Low strength and high brittleness; low flexural strength	[150]
Membrane	Nondegradable membrane	Polytetrafluoroethylene (PTFE)	Synthetic polymer material	Excellent mechanical properties; high biocompatibility; strong chemical and thermal stability; low surface friction	It is not degradable and needs to be removed by a second operation. Dehiscence affects tissue regeneration; the application scope is limited	[151]
	Degradable absorbent membrane	Natural collagen membrane	Natural collagen	Excellent shielding performance; degradable; low biotoxicity; no need for a second operation	Poor mechanical stability; fast degradation rate; tissue adhesion is low	[151, 152]
		A compound of polyester, polywater, and polyurethane	Synthetic polymer	Biodegradation is controllable; high mechanical strength; drug encapsulation	Low biological activity; low hydrophobicity	[153, 154]
		PCL/PLA/CA electrospinning nanofiber membrane	Nanofiber membrane	Antibacterial activity; strong ability to organize and combine; excellent bone conductivity	The cost is high; complex preparation	[155]
		Polyamide-6/chitosan fiber membrane	Nanofiber membrane	Strong biocompatibility; the double-layer structure allows the membrane to have different surface properties, acting as an insulator while allowing nutrients to penetrate	The preparation process is complex and requires a combination of electrospinning, solvent casting, and evaporation	[156]
Mesh	Synthetic compound	Hydroxyapatite, etc.	Inorganic compound	Controllable porosity; can adapt to a certain range of stress changes; to ensure the normal metabolism of tissues	The mechanical strength is poor, which needs to be toughened by adding sintering additives, whiskers, second particles, etc.	[157]

Note. GelMA: methacrylate gelatin; HEMA: 2-hydroxyethyl methacrylate; PVA: polyvinyl alcohol; PEG: polyethylene glycol; GelMA-dHAMMA: methylpropenyl acylated gelatin-methacrylate complex hydrogels; PCL/PLA/CA: electrospinning nanofiber membrane: electrospinning nanofiber membranes prepared by polycaprolactone/polylactic acid/cellulose acetate polymers.