Table 3.

Summary of distinct approaches of collagen extraction.

Methods	Principles	Advantages	Disadvantages	Refs.
Acidic treatment	After lipid and protein removal, the sample is immersed in a diluted acidic solution, in which case, salt bonds between collagen molecules are broken, allowing the collagen to be solubilized. Acid-soluble collagen is obtained following salinization, dialysis, and other processes.	1.Moderate processing temperature 2.Preservation of intact triple helix structure. 3.Capability to maintain excellent biological properties.	1.Preservation of telopeptides resulting in a high risk of immunogenicity. 2.Log extraction time. 3.Low yield.	[75,76]
Enzymatic treatment	The protease is used to restrictively cleave the terminal peptide of collagen. The remaining body part is soluble in neutral or acidic solutions, resulting in the extraction of enzyme-soluble collagen.	1.Maintenance of intact triple helix structure. 2.High bioactivity. 3.Shortened reaction time. 4.High collagen purity. 5.Satisfying physiochemical properties.	1.Risk of immunogenicity.	[77,78]
Genetic engineering	The technology of designing, enzymatic cleavage, and splicing of human collagen genes with specific sequences, ligating vectors and then transferring them into engineered cells, and expressing the produced collagen and its analogs by fermentation. Different expression systems, such as E. coli, yeast, insect cells, and transgenic crops, are involved.	1.Higher bioactivity 2.Better water solubility 3.Lower risk of immunogenicity and pathogens 4.No cytotoxicity 5.Higher denaturation temperature 6.Ease of transportation and storage	1.Long process 2.High technical difficulty 3.High cost 4.Low yield.	[79]