journal article·2021-12Open access

An intrinsically bioactive hydrogel with on-demand drug release behaviors for diabetic wound healing

Bin Hu, Mingzhu Gao, Kofi Oti Boakye-Yiadom, William Ho, Wei Yu, Xiaoyang Xu, Xue-Qing Zhang

Bioactive Materials· Volume 6· Issue 12

Abstract

Prolonged, intense inflammation and excessive oxidative stress hinder diabetic wounds from healing normally, leading to disorders downstream including the postponement of re-epithelialization and extracellular matrix (ECM) formation. Herein, we report a hyaluronic acid (HA) and chitosan based hydrogel (OHA-CMC) with inherent antibacterial and hemostatic activities fabricated via Schiff base reaction. By encapsulating nanotechnologically-modified curcumin (CNP) and epidermal growth factor (EGF) into the hydrogel, OHA-CMC/CNP/EGF exhibited extraordinary antioxidant, anti-inflammatory, and migration-promoting effects in vitro. Meanwhile, OHA-CMC/CNP/EGF presented on-demand drug release in synchrony with the phases of the wound healing process. Specifically, curcumin was rapidly and constantly released to alleviate inflammation and oxidative stress in the early phase of wound healing, while a more gradual and sustained release of EGF supported late proliferation and ECM remodeling. In a diabetic full-thickness skin defect model, OHA-CMC/CNP/EGF dramatically improved wound healing with ideal re-epithelialization, granulation tissue formation, and skin appendage regeneration, highlighting the enormous therapeutic potential this biomaterial holds as a diabetic wound dressing.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Wound Healing and Treatments · Diabetic Foot Ulcer Assessment and Management · Pressure Ulcer Prevention and Management

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

References (55)

Show source-provided references
1. Diabetic foot ulcers and their recurrence10.1056/NEJMra1615439 ↗
2. Treatment for diabetic foot ulcers10.1016/S0140-6736(05)67699-4 ↗
3. Crafting polymeric and peptidic hydrogels for improved wound healing10.1002/adhm.201900104 ↗
4. Recent advances on the development of wound dressings for diabetic foot ulcer treatment-A review10.1016/j.actbio.2013.03.033 ↗
5. Engineered human vascularized constructs accelerate diabetic wound healing10.1016/j.biomaterials.2016.06.009 ↗
6. Acellular and cellular approaches to improve diabetic wound healing10.1016/j.addr.2018.07.019 ↗
7. Blocking interleukin-1 beta induces a healing-associated wound macrophage phenotype and improves healing in type 2 diabetes10.2337/db12-1450 ↗
8. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing10.1038/nm.3887 ↗
9. Sulfated chitosan rescues dysfunctional macrophages and accelerates wound healing in diabetic mice10.1016/j.actbio.2020.09.035 ↗
10. Diabetic wound regeneration using peptide-modified hydrogels to target re-epithelialization10.1073/pnas.1612277113 ↗
11. Redox signaling in diabetic wound healing regulates extracellular matrix deposition10.1089/ars.2017.7263 ↗
12. Biological properties of curcumin-cellular and molecular mechanisms of action10.1080/10408690490424702 ↗
13. Curcumin as a wound healing agent10.1016/j.lfs.2014.08.016 ↗
14. Nanoencapsulation, an efficient and promising approach to maximize wound healing efficacy of curcumin: a review of new trends and state-of-the-art10.1016/j.colsurfb.2016.11.036 ↗
15. Curcumin, a multifaceted hormetic agent, mediates an intricate crosstalk between mitochondrial turnover, autophagy, and apoptosis
16. Epidermal growth factor therapy and wound healing - past, present and future10.1016/S1479-666X(08)80114-X ↗
17. Heparin desulfation modulates VEGF release and angiogenesis in diabetic wounds10.1016/j.jconrel.2015.10.028 ↗
18. EGF containing gelatin-based wound dressings10.1016/S0142-9612(00)00287-8 ↗
19. Biomimetic nanoengineered scaffold for enhanced full-thickness cutaneous wound healing10.1016/j.actbio.2021.01.029 ↗
20. Photo -responsive supramolecular hyaluronic acid hydrogels for accelerated wound healing10.1016/j.jconrel.2020.04.014 ↗
21. Growth factor loaded in situ photocrosslinkable poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/gelatin methacryloyl hybrid patch for diabetic wound healing10.1016/j.msec.2020.111519 ↗
22. EGF and curcumin co-encapsulated nanoparticle/hydrogel system as potent skin regeneration agent10.2147/IJN.S104350 ↗
23. A human epidermal growth factor-curcumin bandage bioconjugate loaded with mesenchymal stem cell for in vivo diabetic wound healing10.1016/j.msec.2020.110751 ↗
24. An EGF- and curcumin-Co-encapsulated nanostructured lipid carrier accelerates chronic-wound healing in diabetic rats10.3390/molecules25204610 ↗
25. Highly elastic biodegradable single-network hydrogel for cell printing10.1021/acsami.8b01294 ↗
26. Bioinspired multifunctional hybrid hydrogel promotes wound healing
27. Advances in engineering hydrogels10.1126/science.aaf3627 ↗
28. A dual-bioresponsive drug-delivery depot for combination of epigenetic modulation and immune checkpoint blockade
29. Injectable stem cell-laden supramolecular hydrogels enhance in situ osteochondral regeneration via the sustained co-delivery of hydrophilic and hydrophobic chondrogenic molecules10.1016/j.biomaterials.2019.04.031 ↗
30. Reducing posttreatment relapse in cleft lip palatal expansion using an injectable estrogen-nanodiamond hydrogel10.1073/pnas.1704027114 ↗
31. A multi-functional implant induces bone formation in a diabetic model
32. Silk fibroin/chondroitin sulfate/hyaluronic acid ternary scaffolds for dermal tissue reconstruction10.1016/j.actbio.2013.02.016 ↗
33. Adhesive hemostatic conducting injectable composite hydrogels with sustained drug release and photothermal antibacterial activity to promote full-thickness skin regeneration during wound healing10.1002/smll.201900046 ↗
34. Wound healing and antimicrobial effect of active secondary metabolites in chitosan-based wound dressings: a review10.1016/j.carbpol.2020.115839 ↗
35. Injectable in situ forming biodegradable chitosan-hyaluronic acid based hydrogels for cartilage tissue engineering10.1016/j.biomaterials.2008.12.080 ↗
36. Injectable in situ self-cross-linking hydrogels based on poly(L-glutamic acid) and alginate for cartilage tissue engineering10.1021/bm501313t ↗
37. On-demand dissolvable self-healing hydrogel based on carboxymethyl chitosan and cellulose nanocrystal for deep partial thickness burn wound healing10.1021/acsami.8b14526 ↗
38. Degradable conductive injectable hydrogels as novel antibacterial, anti-oxidant wound dressings for wound healing10.1016/j.cej.2019.01.028 ↗
39. An injectable and instant self-healing medical adhesive for wound sealing10.1021/acsami.0c01022 ↗
40. Dopant-free hydrogels with intrinsic photoluminescence and biodegradable properties10.1002/adfm.201802607 ↗
41. In vivo and in vitro tracking of erosion in biodegradable materials using non-invasive fluorescence imaging10.1038/nmat3095 ↗
42. Engineering and application perspectives on designing an antimicrobial surface10.1021/acsami.9b19992 ↗
43. Chitosan-thioglycolic acid as a versatile antimicrobial agent10.1021/bm3018593 ↗
44. Nanoenzyme-reinforced injectable hydrogel for healing diabetic wounds infected with multidrug resistant bacteria10.1021/acs.nanolett.0c01371 ↗
45. Efficient angiogenesis-based diabetic wound healing/skin reconstruction through bioactive antibacterial adhesive ultraviolet shielding nanodressing with exosome release10.1021/acsnano.9b03656 ↗
46. Encapsulation of curcumin nanoparticles with MMP9-responsive and thermos-sensitive hydrogel improves diabetic wound healing10.1021/acsami.8b03868 ↗
47. Potent laminin-inspired antioxidant regenerative dressing accelerates wound healing in diabetes10.1073/pnas.1804262115 ↗
48. Structure-property relationships of trimetazidine derivatives and model compounds as potential antioxidants10.1016/S0891-5849(98)00072-0 ↗
49. Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes10.1038/ncomms13393 ↗
50. Hierarchical micro/nanofibrous scaffolds incorporated with curcumin and zinc ion eutectic metal organic frameworks for enhanced diabetic wound healing via anti-oxidant and anti-inflammatory activities10.1016/j.cej.2020.126273 ↗
51. Biochemical characterization of Nostoc sp. exopolysaccharides and evaluation of potential use in wound healing10.1016/j.carbpol.2020.117303 ↗
52. Controlled delivery of heparin-binding EGF-like growth factor yields fast and comprehensive wound healing10.1016/j.jconrel.2012.11.004 ↗
53. The mouse excisional wound splinting model, including applications for stem cell transplantation10.1038/nprot.2013.002 ↗
54. Re-epithelialization of adult skin wounds: cellular mechanisms and therapeutic strategies10.1016/j.addr.2018.06.019 ↗
55. Therapeutic effect of the epidermal growth factor on diabetic foot ulcer and the underlying mechanisms