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Table 1 Natural materials for cartilage tissue engineering. Advantages and disadvantages

From: Current concepts and perspectives for articular cartilage regeneration

Natural origin scaffolds

Advantages

Disadvantages

Hyaluronic acid

Anionic, non-sulfated glycosaminoglycan (GAG) is present in cartilage ECM. Supports cell attachment through surface receptors like CD44ECM

Poor mechanical properties, rapid degradation

Chondroitin sulfate

Sulfated GAG is present in cartilage ECM with anti- inflammatory activity, and a role in cell signaling. Easy to be functionalized

Poor mechanical properties, rapid degradation

Alginate

Negatively charged polysaccharide extracted from brown algae and bacterial sources. High functionality, fast cross-linking, low cost, injectable for bioprinting, structural similarity to GAGs

Poor mechanical strength, low cell- matrix interaction, varying levels of purity due to source variability, immunogenicity

Agarose

A marine polysaccharide obtained from seaweed. It presents excellent biocompatibility, good stiffness and viscoelasticity. High functionality, thermoreversible gelation, low cost, structural similarity to GAGs

Limited mechanical performance, low bioactivity, poor cell attachment

Chitosan

An amino polysaccharide polymer derived from chitin and the wastes of the seafood industry. Biocompatible and biodegradable. It possesses antibacterial ability

Poor water solubility in physiological conditions, potential allergenic risks, inferior mechanical properties, low cell adhesiveness, and potential allergenic reactions due to its origin

Gellan gum

A linear negatively charged polysaccharide produced by the Sphingononas group bacteria; pH and temperature responsiveness, structural similarity to GAGs

Weak mechanical strength, poor stability, low bioactivity, relatively high gelation temperature, small temperature window

Collagen

The main protein component in natural cartilage, displays great biocompatibility and biodegradation without causing inflammation

Poor mechanical properties, potential of immunogenicity, high cost, limited sterilizability

Gelatin

A derivative of collagen by partial hydrolysis with much lower antigenicity Biologically active for cellular interaction, low immunogenicity in comparison to collagen, ease of processing and functionalization

Poor mechanical properties, rapid degradation, low thermal stability

Silk fibroin

The major protein component of natural silk. High mechanical strength, low immunogenicity, morphologic flexibility, good sterilizability, usable for cartilage bioprinting, easily available, biocompatible, biodegradable

Source variability, low biodegradability

Fibrin

Fibrin is a blood protein, well known for its role in clot formation, justifying its use in clinical practice as a hemostatic or a sealant agent. Hydrogels can be prepared from fibrinogen by the enzymatic treatment of thrombin; the advantages are excellent biocompatibility and biodegradability

Weak mechanical properties

Cellulose

One of many polymers found in nature, may enter the composition of carboxymethyl cellulose, and in turn, hydrogel by specific processes

Low integration. No degradability