Table 3.
Injectable hydrogels for future diabetic foot ulcer (DFU) management.
| Reference | Composition | Main | Aim | Study Design | Result | Conclusion |
|---|---|---|---|---|---|---|
| Qu et al. 2019 | N-carboxyethyl chitosan (CEC) Oxidized hyaluronic acid-graft-aniline tetramer (OHA-AT) |
Amoxicillin | To develop multifunctional injectable hydrogel -anti-oxidant -antibacterial -electroactive |
In vivo In vitro |
Wound: (Day 15) amoxicillin loaded hydrogel (p < 0.05) Antimicrobial: (Day 3) Highest cumulative zone of inhibition (p < 0.05) |
In vivo: accelerate wound healing rate than commercialized product In vitro: Effective antibacterial effect |
| Zhao et al. 2017 | pH and Glucose Dual-Responsive | Bovine insulin | To develop sustained and pH/glucose-triggered drug release | In vivo | Wound: 58 ± 2% of collagen deposition, 2.41-fold population of red CD31-positive cells compared to control | In vivo: Infiltration of inflammation, accelerate neovascularization, collagen disposition |
| Qian et al. 2020 | Platelet-Rich Plasma Release | Platelet-rich plasma (PRP) | To develop self-healing injectable hydrogel | In vivo In vitro |
Wound: (day 21) increased the nerve density (p > 0.05) and (day 7) higher healing rate | In vivo: Accelerate collagen deposition, wound healing, angiogenesis, neovascularization In vitro: support human dermal fibroblast (HDF), Human Umbilical Vein Endothelial cells (HUVEC), Human Umbilical Mesenchymal Stem Cells (HUMSC) proliferation. |
| Jin et al., 2020 | Hypoxia-Induced Conductive | Vanillin-grafted gelatin Laccase (Lac) |
To develop injectable hydrogel with hypoxic microenvironment ability to assist tissue regeneration. | In vivo | Wound: HIF-1α pathway activation, 95% wound closure rate (21 days) compared to control < 75% Subcutaneous study: proangiogenic factors secretion < 0.05 (day 7) |
Regulate stem cell plasticity, neovascularization, collagen deposition, hair follicle reconstruction, gene expression acceleration |
| Wang et al., 2019 | Antibacterial exosomes | Adipose mesenchymal stem cells exosomes (AMSCs-Exo) | Evaluate angiogenesis and antibacterial ability of FHE@exo hydrogel | In vitro In vivo |
HUVEC: formation of 45 vessels compared to controlled group (20 vessels), elevated alpha-smooth muscle actin (α-SMA) expression Wound: smaller wound closure, thickest granulation tissue (day 14) in the treatment group Antibacterial study: no bacterial infection during the experimental period compared to control |
In vitro: accelerate proliferation, migration, angiogenesis In vivo: less scar formation, wound healing acceleration. |
| Chen et al. 2019 | Thiolated polyethylene glycol (SH-PEG) Silver nitrate (AgNO3) |
Desferrioxamine (DFO) | Evaluate angiogenesis and antibacterial abilities of DFO on HUVEC and diabetic-induced rats. | In vitro In vivo |
HUVEC: extensive vascular tubule formations after treatment Wound: dry and 50% reduction compared to control (day 7) Antibacterial study: minimal intensity Staphylococcus aureus compared to control |
Invitro: Show antibacterial and angiogenic capability. In vivo: Proven antibacterial and enhance angiogenesis. |
| Bai et al. 2020 | Bone marrow mesenchymal stem cells (BM-MSCs) growth factors. | Hyaluronic acid (HA) Adipic acid dihydrazide (ADH) |
Evaluate inflammatory microenvironment in diabetic induce rats | In vivo | Wound: Significantly smaller (p < 0.05) wound, growth factors elevate (p < 0.01) at day 15. | In vivo: Formation of granulation tissue, collagen deposition, nucleated cell proliferation, neovascularization |
| Li et al. 2020 | Polyethylene glycol diacrylate (PEGDA) | Nanoparticles (copper + sodium alginate) |
Evaluate angiogenic properties of hydrogel on diabetic induce mice. | In vitro In vivo |
Antibacterial study: inhibit * p < 0.05 and ** p < 0.01 of Staphylococcus aureus and Escherichia coli, respectively. Wound: Peaked blood flow at day 7 with the treatment group. |
In vitro: Accelerate proliferation and angiogenesis property of endothelia cells (EPCs) In vivo: Promote neovascularization, collagen deposition, and wound healing acceleration |
| Wang et al. 2020 | Nanoezyme- Reinforced |
Insulin manganese dioxide (MnO2) nanosheet |
To develop multifunctional injectable hydrogel | In vivo | Wound: (Day 14) No scar tissue Antibacterial: (Day 14) nearly 100% reduction of bacterial colonies |
In vivo: synergistically diminished inflammatory responses, stimulated angiogenesis, accelerated cell proliferation, promoted granulation tissue formation and extracellular matrix (ECM) deposition |