Table 2 Characteristics of functional hydrogels and their roles in cell-based applications

Alginate (Alg)

Alg

CPA

Physical (Calcium-Alg coordination)

-

E: 1.2 GPa

-

-

-

hUCMSCs

Bone regeneration

CPA maintained the injectability of the paste and enhanced the mechanical strength

²²⁶

Alg-Fibrin

-

Physical (Calcium-Alg coordination, Interpenetrating networks)

Fibrin

-

12 ~23 nm

24 h to days

Alginate lyase

-hMSCs

-hECs

Formation of a capillary network

Fibrin exhibited adhesive properties

⁷⁹⁴

Alg

PLGA-AL

Physical (Calcium-Alg coordination)

-

-

24 h to days

Alginate lyase (β-elimination reaction)

rNPCs

Neural tissue regeneration

PLGA-AL tuned the gel’s degradation rate

⁷⁹⁵

-Alg

-RGD peptide

Alginate lyase

-Covalent

-Physical

RGD peptide

-

-

24 h to days

Alginate lyase (β-elimination reaction)

hOECs

Revascularization (Chick chorioallantoic membrane model)

Alginate lyase accelerated the gel’s degradation rate

⁷⁹⁶

Hyaluronic acid (HA)

-HA

-Methacrylic anhydride

-MBA

-P-aPD-L1

-IL-15

Covalent (Radical polymerization)

IL-15

-

-

Weeks

Hyaluronidase

CAR-T cells

Inhibition of post-surgery tumor recurrence (mouse melanoma resection model)

-P-aPD-L1 blocked the PD-1/PD-L1 pathway

-IL-15 maintained the activity and proliferation of CAR-T cells

²⁸

-HA

-PBA

-Sodium periodate

-Methacrylic anhydride

-

Covalent (Radical polymerization)

PBA

E: 2.6 ~23.2 kPa

-

-

-

rbCCs

Cartilage regeneration

PBA enhanced the interaction of chondrocytes and hydrogel, promoting cell adhesion and aggregation through filopodia

⁷⁹⁷

-HA

-Methacrylate

-

Covalent (Radical polymerization)

-

-

-

Days to weeks

-

hMSCs

Endometrial regeneration (Endometrial injury rat model)

-

⁷⁹⁸

Chitosan (CS)

-CS

-

-

-

50~500 μm

Weeks

-

hT cells

Cancer immunotherapy

-

⁷⁹⁹

-CS

-Dextran

-β-GP

-

Physical (Electrostatic attraction, hydrogen bond interactions)

-

-

18.5~25.4 μm

70% in 4 weeks

Enzyme

hUCMSCs

Myocardial infarction therapy

β -GP reduced chitosan chain polarity, making the hydrogel milder and less cytotoxic

⁸⁰⁰

-CS

-Glyoxal

-Col I

-

Physical (Electrostatic attraction)

Col I

-

-

-

-

hBMSCs

Bone regeneration

-Glyoxal enhanced the mechanical hardness of the hydrogel

-β -GP enhanced hydrogel stability

⁸⁰¹

Collagen (Col)

-Col I

-Methacrylate

-

Covalent (Radical polymerization)

Col I

-

-

20.9%~78.6% at 12 h

Collagenase

-rbMSCs

-rbCCs

Chondrogenesis

Methacrylate-modified gelatin reduced the gel’s degradation rate

⁸⁰²

Col I

-

-

CTX

E: 170–227 Pa

-

-

-

-hADSCs

-hUVECs

Regenerative applications

CTX regulated encapsulated cell fate (apoptosis, adhesion, and migration)

⁸⁰³

-Col I

-Alg

PCL/Gel nanofibers

Physical (Calcium-Alg coordination)

RGD peptide

E: 0.0093~0.25 MPa

-

30% in 7 days

-

rADSCs

Wound dressing (rat wound model)

Nanofibers were used as coverage of the scaffold to improve the mechanical strength of the hydrogel

⁸⁰⁴

Gelatin (Gel)

-Gel

-Methacrylate

EGCG-EF

Covalent (Radical polymerization)

-

-

458 ~519 μm² (pore area)

-

-

-hADSCs

-hDFBs

-hUVECs

Tissue engineering applications

EGCG cleared the free radicals

⁸⁰⁵

-Gel

-YIGSR peptide

-QK peptide

-

Covalent (Esterification reaction)

-YIGSR peptide

-QK peptide

-

-

-

-

-hUVECs

-hGEnCs

Tissue engineering applications

-QK peptide stimulated endothelial cell growth

-YIGSR peptide promoted cell adhesion and migration

⁸⁰⁶

-Gel

-Methacrylate

-Alg

-

Covalent (Radical polymerization)

-

E: 6.0~11.0 kPa

-

Days to weeks

Enzyme

hUVECs

Neovascularization (Hind-limb ischemia mouse model)

-

⁸⁰⁷

Silk fibroin (SF)

-SF

-Col I

-

Physical (Interpenetrating networks)

-

-

-

-

-

hMSCs

Tissue engineering applications

-SF enhanced the mechanical properties

-Collagen provided cell adhesion sites

⁸⁰⁸

-SF

-SF-TA

-Cyclic RGD peptide

-

Covalent (Phenol oxidation reaction)

Cyclic RGD peptide

E: ~300 kPa

20 ~ 35 nm

Days to weeks

Protease

hMSCs

Tissue engineering applications

SF-TA enhanced the hydrogel mechanical stability and resistance to enzymatic degradation

⁸⁰⁹

-SF

-G-TA

-

Covalent (Dityrosine crosslinking)

RGD sequence

E: ~300 kPa

20 ~ 35 nm

Days to weeks

Protease

hMSCs

Tissue engineering applications

G-TA enhanced the hydrogel mechanical stability and resistance to enzymatic degradation

⁸⁰⁹

DNA

-DNA

-SilMA

-RGD peptide

-

-Physical

-Covalent

(Radical polymerization)

RGD peptide

-

527.5 ± 25.55 μm

Weeks

Protease

rBMSCs

Cartilage repair (Cartilage defect rat model)

The DNA constrained the SF to increase its β -fold content, allowing for the precise tuning of the surface stiffness of the hydrogels

⁸¹⁰

-DNA

-IKVAV peptide

- Polyacrylamide

-

Covalent (sulfhydryl-MBS crosslinking chemistry)

IKVAV peptide

-

-

-

-

SH-SY5Y cells

Neuronal regeneration

IKVAV peptide enhanced nerve cell attachment and differentiation

²⁴⁶

-DNA

-Tetraethylene glycol

-

Physical

-

-

<10 μm

24 h

DNase I

-A549 cells

-MCF-7 cells

-HEK 293 cells

3D cell culture

-

⁸¹¹

Poly (ethylene glycol) (PEG)

-PEG-LA-DM

-HA

-

-Physical (Interpenetrating networks)

-Covalent (Radical polymerization)

HA

E: 180-230 kPa

-

Weeks

Hydrolysis

bCCs

Cartilage tissue regeneration

-LA promoted hydrogel degradation and macroscopic tissue deposition

-DM polymerized in situ and bore in vivo forces

⁸¹²

-PEG

-PCL

-

Covalent (acid chloride/alcohol chemistry reaction)

-

E: 2.7~7.1 MPa

-

Weeks

-Hydrolysis

-Enzyme

hCECs

Corneal endothelial regeneration (Impaired ovine corneas model)

PCL was covalently incorporated into hydrogel to provide strong tensile properties

⁸¹³

PEG-g-CS

-

Dynamic covalent (Schiff base reaction)

-

-

0.677±0.049 μm

-

-

Human T cells

Localized glioblastoma immunotherapy

^-

²⁷

Polyvinyl alcohol (PVA)

-PVA

-Gel

-

Physical

RGD sequence

E: 3.8 ~5.2 MPa

-

-

-

-NIH3T3 cells

-HeLa cells

Study cell behavior and function

-

¹⁶

-PVA

-CS

HAp

Physical

HAp

E: 109~248 kPa

-

-

Heat

rBMSCs

Bone repair (Bone defect rabbit model)

HAp enhanced the hydrogel-bone interface binding capacity

²⁵⁷

-PVA

-HA

-

Physical

-

-

-

-

-

hBMSCs

Study cell behavior and function

-

⁸¹⁴

Polyacrylamide (Paam)

-PAAm

-DNA

-BIS

-

-Covalent

-Physical

(Interpenetrating networks)

-

-

-

-

-

HEK cells

Study cell behavior and function

DNA and BIS enhanced the hydrogel mechanical stability

⁸¹⁵

-PAAm

-Alg

-

Covalent (Radical polymerization)

-

-

50-100 μm (Porosity: 91%)

-

-

hBMSCs

Tissue engineering applications

The entangled network of PAAm and Alg polymer chains bringed a higher mechanical strength

⁸¹⁶

PAAm

-

Covalent (Radical polymerization)

-

E: 0.67-44 kPa

-

-

Hydrolysis

hPOD

Developing the renal chip model

-

⁸¹⁷