Table 1.

Summary of natural hydrogels suited for organoid culture.

Hydrogels	Origin	Advantages	Disadvantages	Gelation	Organoid types	Refs.
Collagen	Connective tissue of animals	•Containing cell adhesive domains •Enzymatically degraded •Exhibiting structural and mechanical properties reminiscent of native tissues •Facilitating cell growth and differentiation	•Poor thermal stability •Low mechanical strength	•Physical gelation: Thermal self-assembly •Chemical gelation: Glutaraldehyde, EDC/NHS, photopolymerization (methacrylate, thiol derivatives	•Human mammary gland organoids •Intestinal epithelial organoids •Islet organoids from human induced pluripotent stem cells	[22,23,73,169]
Fibrin	Formed from fibrinogen isolated from the blood system	•Biocompatible •Degradable •Abundant biologically active sites	•High cost •Possibility of human pathogen transmission	•Enzymatic gelation: Thrombin, Factor XIII •Chemical gelation: Glutaraldehyde, EDC/NHS	•Liver organoid from hiPSCs •Epithelial organoids derived from different mouse and human tissues	[20,87,170]
Gelatin	Derived through hydrolytic processes of collagen	•Biocompatible •Low immunogenicity •Owning natural Arg-Gly-Asp (RGD) sequences •Biodegradability	•Temperature exerts a significant impact on its mechanical properties	•Physical gelation: Thermal self-assembly • Chemical gelation: Glutaraldehyde, EDC/NHS, photopolymerization (methacrylate, thiol derivatives) •Enzymatic gelation: Transglutaminase	•Prevascularized bone and liver-like tissue analogs •Human liver epithelial organoids •Colorectal cancer patient-derived xenograft (CRC-PDX) organoid	[92,93,154]
Silk fibroin	Derived from the degumming of silk	•Slow degradability •Cell adhesiveness •Outstanding mechanical properties •Non-toxic •Non-immunogenic •Amenability to convenient surface modification	•Lacks of the RGD sequence, usually limiting cell spreading and growth	•Physical gelation: Self-assembly, ultrasonication, shearing •Chemical gelation: Photopolymerization (methacrylate), irradiation, chemical cross-linking agents (genipin, glutaraldehyde) •Enzymatic gelation: Glutamine transferase, carbonic anhydrase laccase, etc.	•Organoid model of dermal papilla •Tumor Spheroid and Organoid •Kidney organoids	[101,102,171,172]
Alginate	A byproduct of iodine and mannitol extracted from the brown algae kelp or Sargassum	•Good biocompatibility •Low price •Low toxicity	•Low cell adhesion •Uncontrollable degradation	• Physical gelation: Ionic cross-linking, electro-static interaction • Chemical gelation: Glutaraldehyde, EDC/NHS, photopolymerization (methacrylate, thiol deriva-tives	•Human lung organoids •Kidney organoids •Intestinal organoid •Brain Organoid •Cartilage organoids from bovine chondrocytes •Pancreatic islet	[106,109,[173], [174], [175], [176]]
Chitosan	The product of chemical deacetylation of chitin	•Biodegradability •Biocompatibility •Low immunogenicity •Antibacterial, mucoadhesive, and hemostatic properties	•Low solubility in water •High pH sensitivity	•Physical gelation: Self-assembly, shearing •Chemical gelation: Electro static complexation (NaA and CS) •Enzymatic gelation: Fibrinogen, thrombin, etc.	•Islet organoids derived from hiPSCs of human hair follicle •Liver organoids from human hiPSCs	[87,113,114]
Hyaluronic acid	Distributed in connective tissue, joint fluid, ocular vitreous, umbilical cord and other tissue	•Biocompatibility •High hydrophilicity •Multiple biochemical functions	•Poor mechanical properties •Rapid degradability	•Physical gelation: Self-assembly, curing after mixing •Chemical gelation: Photopolymerization (phenyl-2,4,6-trimethylbenzoylphosphinate), irradiation, chemical cross-linking agents (thiol-ene addition crosslinking)	•Organoid model of cardiac tissue •Brain organoids from hiPSCs •Islet organoids •iPSC-derived iAT2s self-assemble into alveolospheres	[[119], [120], [121],177]