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Table 1 Chitosan-based hydrogels

From: Advanced polymer hydrogels that promote diabetic ulcer healing: mechanisms, classifications, and medical applications

System

Substance

Mechanism

Signal pathway

Cell line

Animal

Wound size

Characteristic

Ref.

Chitosan/heparin/poly (γ-glutamic acid)

Superoxide dismutase

Re-epithelialization and collagen deposition (+)

NA

3T3 fibroblasts.

STZ-induced diabetic rat model

Two,1cm

Good rheological, swelling, biocompatibility, antioxidant properties

[128]

Chitosan and PVA

Zn2+, polypyrrole

NA

NA

Fibroblasts

STZ-induced diabetic rat model

Four ,1 cm

Excellent stretch, self-healing, biocompatibility, conductivity, antibacterial activity

[129]

Chitosan/polyurethane/PLGA

BMMNCs

Neovascularization (+); wounds size, inflammation (-)

NA

BMMNCs

STZ-induced diabetic rat model

One,0.6cm

Low cytotoxicity, promote healing

[130]

Quaternized chitosan, benzaldehyde-terminated F108 (F108-CHO)

CORM-401, insulin

Anti-inflammatory, Antibacterial, antioxidative stress (+)

ATP synthesis, activated macrophages proliferation (-); scavenging ROS, the expression of HO-1, the polarization of M1 to M2(+); the rupture of bacterial membranes, mitochondrial dysfunction

L929 cells and HUVECs

STZ-induced diabetic rat model

One,0.8cm

Good tissue adhesion, injectability, self-healing, controllable insulin release ability

[131]

Chitosan and decellularized dermal matrix

Carbon nanodots, hAMSC

Angiogenesis, collagen deposition, wound closure, re-epithelialization, formation of DEJ (+)

ColI(+), ColIII, KRT(-)

Human foreskin fibroblasts

STZ-induced diabetic rat model

One,2cm

Proangiogenic potential, ROS scavenging, hemocompatibility, and moderate antimicrobial activity

[132]

Chitosan/PVA

Perfluorocarbon emulsions, EGF-loaded chitosan nanoparticles, and polyhexamethylene biguanide

Re-epithelization, collagen deposition and maturation (+); inflammatory (-)

IL-8(-)

Human keratinocytes (KERTr cells; ATCC® CRL-2309™)

STZ-induced diabetic rat model

Two,0.8 cm

Oxygen delivery, antibacterial, anti-inflammation, and promotive cell growth

[133]

Chitosan

Mixture of flavonoids isolated from the leaves of Passiflora edulis

Antioxidant defense system (+)

NA

Fibroblasts (L929)

Alloxan-treated rats

One,1cm

Anti-inflammatory, antioxidant

[134]

Quaternized chitosan, Tannic acid

/

Collagen deposition, no scar formation, skin regeneration (+)

NA

Rat skin fibroblast-like (RS1) cells

STZ-induced diabetic rat model

One,1cm (Not mentioned in the text, estimated by pictures)

Good injectability and self-healing, cytocompatibility, hemostatic capability and biodegradability, radical scavenging activity

[135]

Fluorinated Meth acrylamide Chitosan

/

Collagen synthesis, neovascularization (+)

NA

NA

The (db/db) homozygote mice

NA,0.8cm

No bioaccumulation, oxygenating

[136]

Ulvan dialdehyde/chitosan/dopamine

Ag NPs, hUC-MSCs

Cell proliferation and migration (+)

Capase3-dependent BCL2 expression, the activation of PCNA and AKT(+)

NIH/3T3 cells

STZ-induced diabetic rat model

One,1cm

Adequate mechanical properties, swelling capability, adhesiveness, antioxidant, antibacterial ability

[137]

Chitosan

PRP, silk fibroin

Collagen deposition, angiogenesis, and nerve repair (+)

CD34, NF-200(+)

L929 cells, HDFs, HUVECs, HUMSCs

STZ-induced diabetic rat model

One,1cm

Injectable, self-healing, biodegradable

[138]

CS-DA-LAG, PEG-PBA-BA

Metformin, polydopamine-coated reduced graphene oxide

Inflammation (-), angiogenesis (+)

IL-6(-); α-SMA, CD31(+)

HUVECs

Type 2 diabetes rat model

One,0.5cm

pH/glucose dual-responsive, adhesion-enhanced, self-healing, easy-removable, antibacterial, antioxidant, conductive, hemostasis

[139]

PVA/Chitosan

The tibetan eighteen flavor dangshen pills

Collagen deposition (+); Pro-inflammatory cytokines (-)

TNF-α, IL-6, IL-1β (-)

L929 cells, HUVECs

STZ-induced diabetic rat model

Four,1cm

Good rheology, suitable swelling and degradation behavior, excellent biocompatibility and antibacterial activity

[126]

Chitosan

Calcium alginate nanoparticles, AgNPs, fresh blood

Collagen bundle (+)

NA

NA

STZ-induced diabetic rat model

One,1.2cm

Antimicrobial, hemostatic, self-healing, scar free

[125]

Chitosan-PEG

AgNPs

NA

NA

NA

Alloxan-induced diabetic rabbits’ model

Two,2cm

Antioxidant, antibacterial

[127]

Methacrylated chitosan

P. granatum peel crude extract, AgNPs, ethyl acetate fraction

NA

TGF-β1, NF-κB (+)

Human normal cell line (HFB4)

Diabetic rat model

one,1cm

Good mechanical characterization, promote healing

[140]

Benzaldehyde-terminated 4-arm PEG/carboxymethyl chitosan

bFGF

Epithelialization, collagen, hair follicles, neovascularization (+)

Ki67, CD31, CD34 expression (+)

L929 cells

STZ-induced diabetic rat model

One,1cm

Excellent wet-tissue adhesion, self-mending, and antibacterial, biocompatibility and fast hemostasis capacity

[141]

Quaternized chitosan, ε-poly-L-lysine grafted graphene quantum dots, benzaldehyde-terminated four-arm poly (ethylene glycol)

/

The migration and proliferation of fibroblast cell, inactivation of bacteria (+); bacterial membrane (-)

NA

NIH3T3 cells

STZ-induced diabetic rat model

One,1cm

pH sensitivity, self-healing, hemostatic, and biocompatible

[142]

Collagen, Chitosan

Silver nanoparticles

Collagen deposition, hair follicle repair, sebaceous glands formation (+)

VEGF, TGF-b1, IL-1b, and TIMP1 expression (+)

HUVECs

alloxan-induced diabetic rat model

One,0.5cm

Good mechanical properties and biological activity

[143]

Chitosan

Puerarin

Angiogenesis (+); inflammation (-)

MiR-29ab1 mediated inflammatory axis (-)

Mouse mononuclear macrophage leukemia cells (RAW264.7)

STZ-induced diabetic rat model

One,1cm

Anti-inflammatory, promote healing

[144]

Sulfated chitosan

Collagen type I

Re-epithelialization, collagen deposition, neovascularization (+)

IL-4, TGF-β1(+); IL-6(-)

L929 fibroblasts

STZ-induced diabetic rat model

Two, NA

Improving inflammatory microenvironment, regulate macrophage behaviors

[145]

PVA, chitosan, phenylboric acid

Insulin, gelatin microspheres containing celecoxib

Angiogenesis, cell proliferation and migration, hair follicle regeneration (+)

IL-10, VEGF (+); TNF-α, MMP9, AGEs (-)

L929 cells, RAW 264.7 macrophages

STZ-induced diabetic rat model

Two ,0.8cm

Glucose and MMP-9 dual-response, temperature-sensitive, Shape self-adaptive, excellent biocompatibility

[146]

Chitosan

Ag+, Cu2+

cell migration, angiogenesis (+)

IL-10, α-SMA, VEGF, CD31 (+)

HUVECs and mouse fibroblast cells (L929)

STZ-induced diabetic rat model

NA,0.8cm

Injectable, self-healing, and biodegradable, antibacterial

[147]

Chitosan HCl, κ- carrageenan and PVA

Cefotaxime

Angiogenesis, collagen deposition, epidermis regeneration (+)

NA

NIH3T3 fibroblast cells

STZ-induced diabetic rat model

NA,1.5 cm (burn)

Excellent bacterial barrier property, oxygen and water transmission rate, flexibility, mechanical properties

[148]

Pluronic F127 and chitosan

Ce@LTA-NPs

The formation of granulation tissue, re-epithelialization, collagen remodeling (+)

NA

HUVECs,murine macrophage RAW264.7

STZ-induced diabetic rat model

One,2cm

ROS scavenging, clear inflammatory factors, good porosity, stability and biocompatibility

[149]

  1. “(+)” represents upregulated or promoted
  2. “(-)” represents downregulated or suppressed