Table 3.

Advantages and disadvantages of different chondroitin and chondroitin derivatives production methods.

	Animal extraction	Chemical synthesis	Enzymatic production	Microbial production
Substrate cost	Cheap	Expensive	Expensive	Cheap
Shortage of materials	Yes	No	No	No
Presence of contaminants (prions, viruses, growth factors)	Yes	No	No	No
Vegan/ vegetarian	No	Yes	Yes	Yes
Requires feeding co-factors	No	No	Yes	No
Chemical steps to obtain substrates or sulfation	No	Yes	Most times	Sometimes
Stereoselective and regioselective reactions	not applicable	No	Yes	Yes
Time-consuming process	Yes	Yes	Yes, for protein purification	No
Harsh conditions (pH, temperature, pressure)	Yes	Yes	No	No
Scale-up	Limited and expensive	Difficult	Difficult	Easy
Control of degree of sulfation and size	No	Yes	Yes	Yes
Yields	Highest	Low	Lowest	Low
Environmental-friendly process	No	No	Yes	Yes
Possibility to obtain unnatural compounds	No	Yes	Yes	Yes
Final product purification complexity	Very heterogeneous, polydisperse and usually contaminated with other glycosaminoglycans	Easy	Easy	May require cell lysis and purification. For pathogenic hosts, endotoxins need to be removed