Table 1.

Naturally derived and synthetic or semisynthetic hydrogels in biomedical applications

Primary types	Cell scaffolds	Characteristics and advantages	Disadvantages and limitations	Refs.
Natural hydrogels	Matrigel	Collection of collagen, laminin, enactin Multiple growth factors Bioactive sites for cell recognition Good mimic of in vivo cellular conditions Cell phenotype study 3D microenvironment; cytocompatibility; Tunable physical properties.	Complex, chemically not well‐defined scaffold Undefined impurities Unknown amount of growth factors High batch‐to‐batch variation.	[ 35 , 133 ]
	Collagen I Gelfoam hydrogel	Primary extracellular constituent of ECM Rat tail tendon, tendon, and bovine skin Natural hydrogel‐forming proteins Multiple crosslinking methods Similar structure and stiffness to native tissues Enzymatically degradable properties Native instructive cues for cell recognition.	Require acidic solution to dissolve collagen I Batch‐to‐batch variation Limited control over matrix architecture Inability to tailor its composition.	[ 41 , 132 , 144 ]
	Alginate	Linear polysaccharide from brown algae Adhesive ligands for cell attachment Easy cell encapsulation and recovery Biodegradable hydrogel Desired mechanical properties and pore sizes Chemically inert support for cell growth.	Limited cell culture periods Variable stability Mechanical strength The limited modification.	[ 45 , 46 , 214 ]
	Hyaluronic acid (HA)	Major glycosaminoglycan in tumor's ECM Tunable chemical modification Biological relevance to tissue in vivo Versatile chemical crosslinking available HA ligand for receptor recognition.	HA hydrogel does not provide integrin attachment	[ 21 , 136 ]
	Silk fibroin hydrogels	High β‐sheet content and shear thinning Strong adhesive properties Adhesives for medical devices or sensors Therapeutic delivery of (stem) cells	Opaque with the formation of nanocrystallite Low elastic behavior and plastic deformation at strains >10%	[ 224 ]
Semisynthetic hydrogel	GelMA hydrogel	Artificial 3D ECM mimics Gelatin, type I collagen, 70–80% of lysine groups Biocompatibility of natural matrices Reproducibility; Synthetic stability and modularity Tunable properties	Cross‐linked by UV by photoinitiator Teflon mold Amenable stiffness Multiple components	[ 50 , 197 , 225 ]
synthetic polymer hydrogels	PEG	User‐controlled modifications Premodified versions and various molecular weights Engineering different functional ligands Degrade via passive, proteolytic, or user‐directed modes Precise tunability of architecture and stiffness	Cell‐binding moieties Biochemical cues Inert substrate Limited cell recovery	[ 21 , 202 , 226 ]
	PLGA	Reproducible and tunable physicochemical properties Porous biodegradable synthetic scaffolds Control the type and degree of porosity Good cell attachment properties Amenable to large‐scale use.	Cell‐binding sites Protease‐cleavage motifs Inert substrate Limited cell recovery.	[ 132b ]
Synthetic peptide hydrogels	PuraMatrix hydrogel	Artificial designer peptide hydrogel Defined amino acid composition Stable β‐sheet and nanofiber structure Great design flexibility Tailorable with specific motifs Biological functionality of native ECM.	The mechanical properties Low stiffness Appropriate rheology.	[ 10 , 132 , 170 ]
	Biogelx hydrogel	Self‐supporting nanostructural hydrogels Bioinspired low molecular weight hydrogels Short, simple, di‐ or tri‐peptides N‐terminus modified with the aromatic Fmoc Tunable mechanical and chemical properties Decent stiffness and rheology.	Fmoc groups are not normally found in the ECM;	[ 227 ]