Skip to main content
SpringerLink
Log in

Cobalt-based metal–organic framework as a dual cooperative controllable release system for accelerating diabetic wound healing

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Insufficient angiogenesis in the chronic wound of the diabetic is one of the most important causes that making the wound unable to heal itself. In this work, a cobalt-based metal–organic framework (ZIF-67) was introduced as a carrier for loading a pro-angiogenic small molecular drug (dimethyloxalylglycine, DMOG). To achieve a long-term angiogenic therapy on the diabetic wound beds, a dual cooperative controllable release system has been designed by incorporating the drug-loaded ZIF-67 nanoparticles into the micro-patterned PLLA/Gelatin nanofibrous scaffolds. The results showed that DMOG was incorporated into ZIF-67 with a high loading ratio (359.12 mg/g), and the drug-loaded ZIF-67 nanoparticles were well embedded in the circular patterned scaffold. Notably, the DMOG as well as Co ions could continuously release from the scaffold for more than 15 days. The in vitro studies showed that the released Co ions and DMOG from the micropatterned nanofibrous scaffolds could synergistically promote the proliferation, migration and tube formation of the human umbilical vein endothelial cells (HUVECs) by inducing a hypoxia response and upregulating the expression of angiogenesis-related genes such as HIF-1α, VEGF and e-NOS. Furthermore, the in vivo results demonstrated that the composite scaffolds could significantly enhance angiogenesis, collagen deposition and eliminate inflammation in the diabetes wounds. These results indicate that the cobalt-based metal–organic framework as a dual cooperative controllable release system provides a new strategy for enhancing angiogenesis and promoting diabetic wound healing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Brem, H.; Tomic-Canic, M. Cellular and molecular basis of wound healing in diabetes. J. Clin. Invest.2007, 117, 1219–1222.

    CAS  Google Scholar 

  2. Armstrong, D. G.; Boulton, A. J. M.; Bus, S. A. Diabetic foot ulcers and their recurrence. N. Engl. J. Med.2017, 376, 2367–2375.

    Google Scholar 

  3. Moura, L. I. F.; Dias, A. M. A.; Carvalho, E.; De Sousa, H. C. Recent advances on the development of wound dressings for diabetic foot ulcer treatment—A review. Acta Biomater.2013, 9, 7093–7114.

    CAS  Google Scholar 

  4. Zhang, Q. K.; Oh, J. H.; Park, C. H.; Baek, J. H.; Ryoo, H. M.; Woo, K. M. Effects of dimethyloxalylglycine-embedded poly(ε-caprolactone) fiber meshes on wound healing in diabetic rats. ACS Appl. Mater. Interfaces2017, 9, 7950–7963.

    CAS  Google Scholar 

  5. Ren, X. Z.; Han, Y. M.; Wang, J.; Jiang, Y. Q.; Yi, Z. F.; Xu, H.; Ke, Q. F. An aligned porous electrospun fibrous membrane with controlled drug delivery—An efficient strategy to accelerate diabetic wound healing with improved angiogenesis. Acta Biomater.2018, 70, 140–153.

    CAS  Google Scholar 

  6. Li, J.; Wang, X. X.; Zhao, G. X.; Chen, C. L.; Chai, Z. F.; Alsaedi, A.; Hayat, T.; Wang, X. K. Metal-organic framework-based materials: Superior adsorbents for the capture of toxic and radioactive metal ions. Chem. Soc. Rev.2018, 47, 2322–2356.

    CAS  Google Scholar 

  7. Xuan, W. M.; Zhu, C. F.; Liu, Y.; Cui, Y. Mesoporous metal–organic framework materials. Chem. Soc. Rev.2012, 41, 1677–1695.

    CAS  Google Scholar 

  8. Bloch, E. D.; Queen, W. L.; Krishna, R.; Zadrozny, J. M.; Brown, C. M.; Long, J. R. Hydrocarbon separations in a metal-organic framework with open iron(II) coordination sites. Science2012, 335, 1606–1610.

    CAS  Google Scholar 

  9. Wang, Z. B.; Knebel, A.; Grosjean, S.; Wagner, D.; Bräse, S.; Wöll, C.; Caro, J.; Heinke, L. Tunable molecular separation by nanoporous membranes. Nat. Commun.2016, 7, 13872.

    CAS  Google Scholar 

  10. Peters, A. W.; Li, Z. Y.; Farha, O. K.; Hupp, J. T. Toward inexpensive photocatalytic hydrogen evolution: A nickel sulfide catalyst supported on a high-stability metal-organic framework. ACS Appl. Mater. Interfaces2016, 8, 20675–20681.

    CAS  Google Scholar 

  11. Zhuang, Y. X.; Zhang, X. D.; Chen, Q. M.; Li, S. Q.; Cao, H. Y.; Huang, Y. M. Co3O4/CuO hollow nanocage hybrids with high oxidase-like activity for biosensing of dopamine. Mater. Sci. Eng. C.2019, 94, 858–866.

    CAS  Google Scholar 

  12. Wu, M. X.; Yang, Y. W. Metal–organic framework (MOF)-based drug/cargo delivery and cancer therapy. Adv. Mater.2017, 29, 1606134.

    Google Scholar 

  13. Li, H. Y.; Lv, N. N.; Li, X.; Liu, B. T.; Feng, J.; Ren, X. H.; Guo, T.; Chen, D. W.; Stoddart, J. F.; Gref, R. et al. Composite CD-MOF nanocrystals-containing microspheres for sustained drug delivery. Nanoscale2017, 9, 7454–7463.

    CAS  Google Scholar 

  14. Abánades Lázaro, I.; Haddad, S.; Rodrigo-Muñoz, J. M.; Marshall, R. J.; Sastre, B.; Del Pozo, V.; Fairen-Jimenez, D.; Forgan, R. S. Surface-functionalization of Zr-fumarate MOF for selective cytotoxicity and immune system compatibility in nanoscale drug delivery. ACS Appl. Mater. Interfaces2018, 10, 31146–31157.

    Google Scholar 

  15. Zhang, Y.; Sun, P. P.; Zhang, L.; Wang, Z. Z.; Wang, F. M.; Dong, K.; Liu, Z.; Ren, J. S.; Qu, X. G. Silver-infused porphyrinic metal–organic framework: Surface-adaptive, on-demand nanoplatform for synergistic bacteria killing and wound disinfection. Adv. Funct. Mater.2019, 29, 1808594.

    Google Scholar 

  16. Liu, X. P.; Yan, Z. Q.; Zhang, Y.; Liu, Z. W.; Sun, Y. H.; Ren, J. S.; Qu, X. G. Two-dimensional metal-organic framework/enzyme hybrid nanocatalyst as a benign and self-activated cascade reagent for in vivo wound healing. ACS Nano2019, 13, 5222–5230.

    CAS  Google Scholar 

  17. Xiao, J. S.; Zhu, Y. X.; Huddleston, S.; Li, P.; Xiao, B. X.; Farha, O. K.; Ameer, G. A. Copper metal-organic framework nanoparticles stabilized with folic acid improve wound healing in diabetes. ACS Nano2018, 12, 1023–1032.

    CAS  Google Scholar 

  18. Xiao, J. S.; Chen, S. Y.; Yi, J.; Zhang, H. F.; Ameer, G. A. A cooperative copper metal–organic framework-hydrogel system improves wound healing in diabetes. Adv. Fun. Mater.2017, 27, 1604872.

    Google Scholar 

  19. Wang, L. L.; Zhu, H. L.; Shi, Y.; Ge, Y.; Feng, X. M.; Liu, R. Q.; Li, Y.; Ma, Y. W.; Wang, L. H. Novel catalytic micromotor of porous zeolitic imidazolate framework-67 for precise drug delivery. Nanoscale2018, 10, 11384–11391.

    CAS  Google Scholar 

  20. Simonsen, L. O.; Harbak, H.; Bennekou, P. Cobalt metabolism and toxicology—A brief update. Sci. Total Environ.2012, 432, 210–215.

    CAS  Google Scholar 

  21. Pacary, E.; Legros, H.; Valable, S.; Duchatelle, P.; Lecocq, M.; Petit, E.; Nicole, O.; Bernaudin, M. Synergistic effects of CoCl2 and ROCK inhibition on mesenchymal stem cell differentiation into neuron-like cells. J. Cell Sci.2006, 119, 2667–2678.

    CAS  Google Scholar 

  22. Park, K. S.; Ni, Z.; Côté, A. P.; Choi, J. Y.; Huang, R. D.; Uribe-Romo, F. J.; Chae, H. K.; O’Keeffe, M.; Yaghi, O. M. Exceptional chemical and thermal stability of zeolitic imidazolate frameworks. Proc. Natl. Acad. Sci. USA2006, 103, 10186–10191.

    CAS  Google Scholar 

  23. Zheng, M.; Liu, S.; Guan, X. G.; Xie, Z. G. One-step synthesis of nanoscale zeolitic imidazolate frameworks with high curcumin loading for treatment of cervical cancer. ACS Appl. Mater. Interfaces2015, 7, 22181–22187.

    CAS  Google Scholar 

  24. Gao, S. T.; Jin, Y.; Ge, K.; Li, Z. H.; Liu, H. F.; Dai, X. Y.; Zhang, Y. H.; Chen, S. Z.; Liang, X. J.; Zhang, J. C. Self-supply of O2 and H2O2 by a nanocatalytic medicine to enhance combined chemo/chemodynamic therapy. Adv. Sci. 2019, 6, 1902137.

    CAS  Google Scholar 

  25. Zhang, J. L.; Cai, Y. N.; Liu, K. X. Extremely effective boron removal from water by stable metal organic framework ZIF-67. Ind. Eng. Chem. Res.2019, 58, 4199–4207.

    CAS  Google Scholar 

  26. Hu, Y. W.; Song, X. D.; Zheng, Q. L.; Wang, J. N.; Pei, J. F. Zeolitic imidazolate framework-67 for shape stabilization and enhanced thermal stability of paraffin-based phase change materials. RSC Adv.2019, 9, 9962–9967.

    CAS  Google Scholar 

  27. Lin, K. Y. A.; Wu, C. H. Efficient adsorptive removal of toxic amaranth dye from water using a zeolitic imidazolate framework. Water Environ. Res.2018, 90, 1947–1955.

    CAS  Google Scholar 

  28. Yuan, Q.; Bleiziffer, O.; Boos, A. M.; Sun, J. M.; Brandl, A.; Beier, J. P.; Arkudas, A.; Schmitz, M.; Kneser, U.; Horch, R. E. PHDs inhibitor DMOG promotes the vascularization process in the AV loop by HIF-1α up-regulation and the preliminary discussion on its kinetics in rat. BMC Biotechnol.2014, 14, 112.

    Google Scholar 

  29. Jayarama Reddy, V.; Radhakrishnan, S.; Ravichandran, R.; Mukherjee, S.; Balamurugan, R.; Sundarrajan, S.; Ramakrishna, S. Nanofibrous structured biomimetic strategies for skin tissue regeneration. Wound Repair Regen.2013, 21, 1–16.

    Google Scholar 

  30. Xu, H.; Lv, F.; Zhang, Y. L.; Yi, Z. F.; Ke, Q. F.; Wu, C. T.; Liu, M. Y.; Chang, J. Hierarchically micro-patterned nanofibrous scaffolds with a nanosized bio-glass surface for accelerating wound healing. Nanoscale2015, 7, 18446–18452.

    CAS  Google Scholar 

  31. Lv, F.; Wang, J.; Xu, P.; Han, Y. M.; Ma, H. S.; Xu, H.; Chen, S. J.; Chang, J.; Ke, Q. F.; Liu, M. Y. et al. A conducive bioceramic/polymer composite biomaterial for diabetic wound healing. Acta Biomater.2017, 60, 128–143.

    CAS  Google Scholar 

  32. Yin, H. Y.; Wang, J.; Gu, Z. Q.; Feng, W. H.; Gao, M. C.; Wu, Y.; Zheng, H.; He, X. M.; Mo, X. M. Evaluation of the potential of kartogenin encapsulated poly(L-lactic acid-co-caprolactone)/collagen nanofibers for tracheal cartilage regeneration. J. Biomater. Appl.2017, 32, 331–341.

    CAS  Google Scholar 

  33. Lee, C. H.; Hsieh, M. J.; Chang, S. H.; Lin, Y. H.; Liu, S. J.; Lin, T. Y.; Hung, K. C.; Pang, J. H. S.; Juang, J. H. Enhancement of diabetic wound repair using biodegradable nanofibrous metformineluting membranes: In vitro and in vivo. ACS Appl. Mater. Interfaces2014, 6, 3979–3986.

    CAS  Google Scholar 

  34. Xu, H.; Li, H. Y.; Ke, Q. F.; Chang, J. An anisotropically and heterogeneously aligned patterned electrospun scaffold with tailored mechanical property and improved bioactivity for vascular tissue engineering. ACS Appl. Mater. Interfaces2015, 7, 8706–8718.

    CAS  Google Scholar 

  35. Lei, Y. F.; Zouani, O. F.; Rami, L.; Chanseau, C.; Durrieu, M. C. Modulation of lumen formation by microgeometrical bioactive cues and migration mode of actin machinery. Small2013, 9, 1086–1095.

    CAS  Google Scholar 

  36. Xie, J. W.; Liu, W. Y.; MacEwan, M. R.; Yeh, Y. C.; Thomopoulos, S.; Xia, Y. N. Nanofiber membranes with controllable microwells and structural cues and their use in forming cell microarrays and neuronal networks. Small2011, 7, 293–297.

    CAS  Google Scholar 

  37. Jiang, Z.; Li, Z. P.; Qin, Z. H.; Sun, H. Y.; Jiao, X. L.; Chen, D. R. LDH nanocages synthesized with MOF templates and their high performance as supercapacitors. Nanoscale2013, 5, 11770–11775.

    CAS  Google Scholar 

  38. Lü, Y. Y.; Wang, Y. T.; Li, H. L.; Lin, Y.; Jiang, Z. Y.; Xie, Z. X.; Kuang, Q.; Zheng, L. S. MOF-derived porous Co/C nanocomposites with excellent electromagnetic wave absorption properties. ACS Appl. Mater. Interfaces2015, 7, 13604–13611.

    Google Scholar 

  39. Li, H. Y.; Chang, J. Stimulation of proangiogenesis by calcium silicate bioactive ceramic. Acta Biomater.2013, 9, 5379–5389.

    CAS  Google Scholar 

  40. Wu, Y. L.; Quan, Y. C.; Liu, Y. Q.; Liu, K. W.; Li, H. Q.; Jiang, Z. W.; Zhang, T.; Lei, H.; Radek, K. A.; Li, D. Q. et al. Hyperglycaemia inhibits REG3A expression to exacerbate TLR3-mediated skin inflammation in diabetes. Nat. Commun.2016, 7, 13393.

    CAS  Google Scholar 

  41. Ammar, M.; Jiang, S.; Ji, S. F. Heteropoly acid encapsulated into zeolite imidazolate framework (ZIF-67) cage as an efficient heterogeneous catalyst for Friedel-Crafts acylation. J. Solid State Chem.2016, 233, 303–310.

    CAS  Google Scholar 

  42. Chun, N. Y.; Kim, S. N.; Choi, Y. S.; Choy, Y. B. PCN-223 as a drug carrier for potential treatment of colorectal cancer. J. Ind. Eng. Chem.2020, 84, 290–296.

    CAS  Google Scholar 

  43. Yang, Y.; Xia, T.; Chen, F.; Wei, W.; Liu, C. Y.; He, S. H.; Li, X. H. Electrospun fibers with plasmid bFGF polyplex loadings promote skin wound healing in diabetic rats. Mol. Pharmaceutics2012, 9, 48–58.

    Google Scholar 

  44. Arima, Y.; Iwata, H. Effect of wettability and surface functional groups on protein adsorption and cell adhesion using well-defined mixed self-assembled monolayers. Biomaterials2007, 28, 3074–3082.

    CAS  Google Scholar 

  45. Shi, Q. Y.; Luo, X.; Huang, Z. Q.; Midgley, A. C.; Wang, B.; Liu, R. H.; Zhi, D. K.; Wei, T. T.; Zhou, X.; Qiao, M. Q. et al. Cobalt-mediated multi-functional dressings promote bacteria-infected wound healing. Acta Biomater.2019, 86, 465–479.

    CAS  Google Scholar 

  46. Kim, H. H.; Lee, S. E.; Chung, W. J.; Choi, Y.; Kwack, K.; Kim, S. W.; Kim, M. S.; Park, H.; Lee, Z. H. Stabilization of hypoxia-inducible factor-1α is involved in the hypoxic stimuli-induced expression of vascular endothelial growth factor in osteoblastic cells. Cytokine2002, 17, 14–27.

    CAS  Google Scholar 

  47. Okonkwo, U. A.; Dipietro, L. A. Diabetes and wound angiogenesis. Int. J. Mol. Sci.2017, 18, 1419.

    Google Scholar 

  48. Wu, C. T.; Zhou, Y. H.; Fan, W.; Han, P. P.; Chang, J.; Yuen, J.; Zhang, M. L.; Xiao, Y. Hypoxia-mimicking mesoporous bioactive glass scaffolds with controllable cobalt ion release for bone tissue engineering. Biomaterials2012, 33, 2076–2085.

    CAS  Google Scholar 

  49. Namiki, A.; Brogi, E.; Kearney, M.; Kim, E. A.; Wu, T. G.; Couffinhal, T.; Varticovski, L.; Isner, J. M. Hypoxia induces vascular endothelial growth factor in cultured human endothelial cells. J. Biol. Chem.1995, 270, 31189–31195.

    CAS  Google Scholar 

  50. Fan, W.; Crawford, R.; Xiao, Y. Enhancing in vivo vascularized bone formation by cobalt chloride-treated bone marrow stromal cells in a tissue engineered periosteum model. Biomaterials2010, 31, 3580–3589.

    CAS  Google Scholar 

  51. Gao, W.; Sun, L.; Fu, X.; Lin, Z.; Xie, W.; Zhang, W.; Zhao, F.; Chen, X. Enhanced diabetic wound healing by electrospun core-sheath fibers loaded with dimethyloxalylglycine. J. Mater. Chem. B2018, 6, 277–288.

    Google Scholar 

  52. Groenman, F. A.; Rutter, M.; Wang, J. X.; Caniggia, I.; Tibboel, D.; Post, M. Effect of chemical stabilizers of hypoxia-inducible factors on early lung development. Am. J. Physiol. Lung Cell. Mol. Physiol.2007, 293, L557–L567.

    CAS  Google Scholar 

  53. Valarmathi, M. T.; Davis, J. M.; Yost, M. J.; Goodwin, R. L.; Potts, J. D. A three-dimensional model of vasculogenesis. Biomaterials2009, 30, 1098–1112.

    CAS  Google Scholar 

  54. McClure, M. J.; Wolfe, P. S.; Simpson, D. G.; Sell, S. A.; Bowlin, G. L. The use of air-flow impedance to control fiber deposition patterns during electrospinning. Biomaterials2012, 33, 771–779.

    CAS  Google Scholar 

  55. Da Silva, I. R.; Da Tiveron, L. C. R. C.; Da Silva, M. V.; Peixoto, A. B.; Carneiro, C. A. X.; Dos Reis, M. A.; Furtado, P. C.; Rodrigues, B. R.; Rodrigues, V.; Rodrigues, D. B. R. In situ cytokine expression and morphometric evaluation of total collagen and collagens Type I and Type III in Keloid scars. Mediators Inflamm.2017, 2017, 6573802.

    Google Scholar 

  56. Wells, A.; Nuschke, A.; Yates, C. C. Skin tissue repair: Matrix microenvironmental influences. Matrix Biol.2016, 49, 25–36.

    CAS  Google Scholar 

  57. Lai, H. J.; Kuan, C. H.; Wu, H. C.; Tsai, J. C.; Chen, T. M.; Hsieh, D. J.; Wang, T. W. Tailored design of electrospun composite nanofibers with staged release of multiple angiogenic growth factors for chronic wound healing. Acta Biomater.2014, 10, 4156–4166.

    CAS  Google Scholar 

  58. Van Putte, L.; De Schrijver, S.; Moortgat, P. The effects of advanced glycation end products (AGEs) on dermal wound healing and scar formation: A systematic review. Scars, Burns Heal.2016, 2, 2059513116676828.

    Google Scholar 

  59. Garwood, C. S.; Steinberg, J. S.; Kim, P. J. Bioengineered alternative tissues in diabetic wound healing. Clin. Podiatr. Med. Surg.2015, 32, 121–133.

    Google Scholar 

  60. Scholzen, T.; Gerdes, J. The Ki-67 protein: From the known and the unknown. J. Cell. Physiol.2000, 182, 311–322.

    CAS  Google Scholar 

  61. Dalby, M. J.; Gadegaard, N.; Tare, R.; Andar, A.; Riehle, M. O.; Herzyk, P.; Wilkinson, C. D. W.; Oreffo, R. O. C. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat. Mater.2007, 6, 997–1003.

    CAS  Google Scholar 

  62. Eming, S. A.; Martin, P.; Tomic-Canic, M. Wound repair and regeneration: Mechanisms, signaling, and translation. Sci. Transl. Med.2014, 6, 265sr6.

    Google Scholar 

  63. Babensee, J. E.; Anderson, J. M.; McIntire, L. V.; Mikos, A. G. Host response to tissue engineered devices. Adv. Drug Deliv. Rev.1998, 33, 111–139.

    CAS  Google Scholar 

  64. Scholz, C. C.; Cavadas, M. A. S.; Tambuwala, M. M.; Hams, E.; Rodríguez, J.; Von Kriegsheim, A.; Cotter, P.; Bruning, U.; Fallon, P. G.; Cheong, A. et al. Regulation of IL-1β-induced NF-κB by hydroxylases links key hypoxic and inflammatory signaling pathways. Proc. Natl. Acad. Sci. USA2013, 110, 18490–18495.

    CAS  Google Scholar 

  65. Bandarra D.; Biddlestone J.; Mudie S.; Müller, H. A. J.; Rocha, S. HIF-1α restricts NF-κB-dependent gene expression to control innate immunity signals. Dis. Models Mech.2015, 8, 169–181.

    Google Scholar 

  66. Wang C.; Sun H. R.; Song Y.; Ma Z. S.; Zhang G.; Gu X. H.; Zhao L. Pterostilbene attenuates inflammation in rat heart subjected to ischemia-reperfusion: Role of TLR4/NF-κB signaling pathway. Int. J. Clin. Exp. Med.2015, 8, 1737–1746.

    Google Scholar 

Download references

Acknowledgements

This work was supported by the Natural Science Foundation of Shanghai (No. 19ZR1437800).

Author information

Author notes

  1. Jiankai Li, Fang Lv, and Jinxiu Li contributed equally to this work.

Authors and Affiliations

  1. College of Chemical and Materials Sciences, Shanghai Normal University, No.100 Guilin Road, Shanghai, 200234, China

    Jiankai Li, Jinxiu Li, Qinfei Ke & He Xu

  2. Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Science and School of Life Science, East China Normal University, Shanghai, 200241, China

    Fang Lv, Yuxin Li, Jingduo Gao & Jian Luo

  3. School of Materials Science and Engineering, Shanghai Institute of Technology, No. 120 Caobao Road, Shanghai, 200235, China

    Qinfei Ke

  4. Southern Medical University Affiliated Fengxian Hospital, 6600 Nanfeng Road, Shanghai, 201499, China

    Fang Lv & Feng Xue

Authors
  1. Jiankai Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fang Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jinxiu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuxin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jingduo Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jian Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Feng Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qinfei Ke
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. He Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Feng Xue, Qinfei Ke or He Xu.

Electronic Supplementary Material

12274_2020_2846_MOESM1_ESM.pdf

Cobalt-based metal–organic framework as a dual cooperative controllable release system for accelerating diabetic wound healing

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, J., Lv, F., Li, J. et al. Cobalt-based metal–organic framework as a dual cooperative controllable release system for accelerating diabetic wound healing. Nano Res. 13, 2268–2279 (2020). https://doi.org/10.1007/s12274-020-2846-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-020-2846-1

Keywords

Search

Navigation