Table 3.

Biologically Derived Scaffold Solutions for Three-Dimensional Cell Culture

Polymer	Description	Example uses	Considerations
Fibrin	Thrombin and Fibrinogen can be mixed to rapidly form a crosslinked hydrogel.	EHM122 Heart patches252 EHTs63	Not immediately physiologically relevant to the heart's matrix. This material has an RGD charged amino acid sequence that readily allows cells to bind to its surface.
Collagens	Collagen stored under acidic conditions to prevent crosslinking is neutralized, mixed with cells, and heated to crosslink.	EHTs63	Physiologically relevant
Matrigel	A combination of proteins, glycoproteins, and cytokines derived from lysed mouse sarcomas, producing a liquefied basement membrane. When heated above 14°C, it crosslinks and forms a hydrogel. Its major components are laminin and collagen IV.	EHTs63 Pacemaker cardiomyocytes with vascularization253	An imperfectly characterized substance that will vary from batch to batch.
Other biologically derived hydrogels	Hyaluronic acid, gelatin, chitosan, alginate, and dozens of other proteins, glycoproteins, and GAGs have been used to form hybrid biodegradable scaffolds.	Alginate gels254 Gelatin gels255 Chitosan gels256	These materials have tunable characteristics, such as pore size and stiffness, which make them useful for adding unusual properties, including timed biodegradation or extremely low cost.
Biologically modified hydrogels	The extracellular matrix is not perfectly uniform, and certain pathological and healthy conditions lead to postprocessing. Some of these modified proteins have superior properties for tissue engineering.	Glycated collagen with improved stiffness257 UV-denatured collagen with improved stiffness258	There are many permutations of hydrogel bases and modifications, some of which are highly specialized for specific projects.

EHM, engineered heart muscle.