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Table 2 HA-based hydrogel

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.

Thiolated HA

Silver-lignin nanoparticles (Ag@Lig NPs)

Angiogenesis (+)

MPO, MMPs, ROS (-)

Keratinocytes (HaCaT cell line)

STZ-induced diabetic rat model

Two,0.2cm

Shear- thinning and self-healing, antibacterial and antioxidant, tunable physico-mechanical properties and degradation rate

[159]

HA grafted with methacrylic anhydride and N-(2-aminoethyl)-4-[4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy]-butana-mide (NB) groups

Amnion-derived conditioned medium (AM-CM)

Mcrophage polarization, promoting angiogenesis (+)

NA

HUVECs, macrophages from the bone marrow of C57BL/6 mice, fibroblasts

The db/db mice

Two, NA

Excellent mechanical properties, elasticity, biocompatibility, tissue adhesion

[157]

HA, Pullulan, Pluronic® F127

Curcumin

Reepithelization, angiogenesis, collagen deposition (+)

NA

3T3-L1 fibroblasts cells

STZ-induced diabetic rat model

NA, 2 cm

Injectable, good rheological and mechanical properties, sustained drug release

[160]

HAMA, PBA

Catechin

Antioxidant enzyme activity, collagen deposition, angiogenesis (+); inflammatory responses, ROS levels (-)

VEGF, CD31, IL-10 expression (+); IL-6 (-)

Fibroblasts

STZ-induced diabetic rat model

One, 1cm

Glucose-responsive, antioxidant, self-healing

[161]

Oxidized dextran, antimicrobial peptide-modified HA

PRP

Collagen deposition, angiogenesis (+); inflammation (-)

TGF-β1, VEGF (+); TNF-α, IL-1β and IL-6(-)

L929 fibroblast cells

The db/db mice

Two,0.8 cm

Wide-spectrum antibacterial, good biocompatibility, stable rheological properties, biodegradability,

[162]

HA

Paeoniflorin

Angiogenesis, re-epithelialization, collagen deposition (+); inflammation (-)

The transition of macrophages from M1 to M2(+)

L929 cells (mouse fibroblasts)

STZ-induced diabetic rat model

Two full-thickness wounds (~0.3 cm2) per animal

Promote healing

[156]

HA, PBA, polyethylene glycol diacrylates

Myricetin

Angiogenesis, tissue remodeling (+); inflammatory response (-)

IL-10, VEGF, CD 31(+); IL-6(-)

NIH 3T3 cells

STZ-induced diabetic rat model

One, 0.8 cm

Glucose-responsive drug release

[163]

HA, heparin

Micellization curcumin

Re-epithelialization and collagen deposition (+)

The transition of macrophages from M1 to M2(+)

L929 cells

STZ-induced diabetic rat model

Two, 0.8cm

Good viscoelasticity and self-healing properties, excellent ROS scavenging ability and anti-inflammatory

[164]

HA, collagen

Gelatin encapsulated metformin microspheres

Collagen deposition (+); inflammation (-)

The transition of macrophages from M1 to M2(+)

Mouse NIH-3T3 cells and RAW 264.7 cells

High sugar and high-fat feed rats

Two ,1cm

pH-responsive, anti- inflammatory

[165]

Oxidized HA, (PBAimBF4)

NA

NA

VEGF (+); TNF-α (-)

L929 cells

Type I diabetes rat model

One,0.8cm

Injectable, satisfactory mechanical properties and flexibility, suitable conductivity and biocompatibility

[166]

HHA, PVA

M2 phenotype macrophages (MΦ2), Cu2+

Inflammation (-)

the transition of macrophages from M1 to M2(+)

Mouse fibroblast cell (L929), HUVECs, and mouse macrophage cells (Raw 264.7)

STZ-induced diabetic rat model

A 7mm thick wound on the back

Promote healing

[167]

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