Skip to main content

Role of Graphene Family Nanomaterials in Skin Wound Healing and Regeneration

  • Chapter
  • First Online:
Multifaceted Biomedical Applications of Graphene

Abstract

Owing to astonishing properties such as the large surface area to volume ratio, mechanical stability, antimicrobial property, and collagen crosslinking, graphene family nanomaterials (GFNs) have been widely used in various biomedical applications including tissue regeneration. Many review literatures are available to compile the role of GFNs in cardiac, bone, and neuronal tissue regeneration. However, the contribution of GFNs in skin wound healing and tissue regeneration was not yet discussed. In the present review, we have highlighted the properties of GFNs and their application in skin wound healing. In addition, we have included challenges and future directions of GFNs in skin tissue regeneration in the portion of conclusion and perspectives.

Iruthayapandi Selestin Raja and Hee Jeong Jang equally contributed to this work.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Alavi A, Sibbald RG, Mayer D, Goodman L, Botros M, Armstrong DG, Woo K, Boeni T, Ayello EA, Kirsner RS (2014) Diabetic foot ulcers: part I. pathophysiology and prevention. J Am Acad Dermatol 70(1):1. e1–18; quiz 19–20

    Article  PubMed  Google Scholar 

  • Anisha BS, Biswas R, Chennazhi KP, Jayakumar R (2013) Chitosan-hyaluronic acid/nano silver composite sponges for drug resistant bacteria infected diabetic wounds. Int J Biol Macromol 62:310–320

    Article  CAS  PubMed  Google Scholar 

  • Ansell DM, Campbell L, Thomason HA, Brass A, Hardman MJ (2014) A statistical analysis of murine incisional and excisional acute wound models. Wound Repair Regen 22(2):281–287

    Article  PubMed  PubMed Central  Google Scholar 

  • Arya AK, Tripathi R, Kumar S, Tripathi K (2014) Recent advances on the association of apoptosis in chronic non healing diabetic wound. World J Diabetes 5(6):756–762

    Article  PubMed  PubMed Central  Google Scholar 

  • Balañá ME, Charreau HE, Leirós GJ (2015) Epidermal stem cells and skin tissue engineering in hair follicle regeneration. World J Stem Cells 7(4):711–727

    Article  PubMed  PubMed Central  Google Scholar 

  • Bao R, Tan B, Liang S, Zhang N, Wang W, Liu W (2017) A Ï€-Ï€ conjugation-containing soft and conductive injectable polymer hydrogel highly efficiently rebuilds cardiac function after myocardial infarction. Biomaterials 122:63–71

    Article  CAS  PubMed  Google Scholar 

  • Bramini M, Sacchetti S, Armirotti A, Rocchi A, Vázquez E, León Castellanos V, Bandiera T, Cesca F, Benfenati F (2016) Graphene oxide nanosheets disrupt lipid composition, Ca2+ homeostasis, and synaptic transmission in primary cortical neurons. ACS Nano 10(7):7154–7171

    Article  CAS  PubMed  Google Scholar 

  • Cha C, Shin SR, Gao X, Annabi N, Dokmeci MR, Tang XS, Khademhosseini A (2014) Controlling mechanical properties of cell-laden hydrogels by covalent incorporation of graphene oxide. Small 10(3):514–523

    Article  CAS  PubMed  Google Scholar 

  • Costa PZ, Soares R (2013) Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox. Life Sci 92(22):1037–1045

    Article  CAS  PubMed  Google Scholar 

  • Daisy ERAC, Rajendran NK, Houreld NN, Marraiki N, Elgorban AM, Rajan M (2020) Curcumin and Gymnema sylvestre extract loaded graphene oxide-polyhydroxybutyrate-sodium alginate composite for diabetic wound regeneration. React Funct Polym 154:104671

    Article  CAS  Google Scholar 

  • Deepachitra R, Ramnath V, Sastry TP (2014) Graphene oxide incorporated collagen–fibrin biofilm as a wound dressing material. RSC Adv 4(107):62717–62727

    Article  CAS  Google Scholar 

  • Eda G, Fanchini G, Chhowalla M (2008) Large-area ultrathin films of reduced graphene oxide as a transparent and flexible electronic material. Nat Nanotechnol 3(5):270–274

    Article  CAS  PubMed  Google Scholar 

  • Fan Z, Liu B, Wang J, Zhang S, Lin Q, Gong P, Ma L, Yang S (2014) A novel wound dressing based on Ag/graphene polymer hydrogel: effectively kill bacteria and accelerate wound healing. Adv Funct Mater 24(25):3933–3943

    Article  CAS  Google Scholar 

  • Frontiñán-Rubio J, Gómez MV, Martín C, González-Domínguez JM, Durán-Prado M, Vázquez E (2018) Differential effects of graphene materials on the metabolism and function of human skin cells. Nanoscale 10(24):11604–11615

    Article  PubMed  Google Scholar 

  • Fu J, Zhang Y, Chu J, Wang X, Yan W, Zhang Q, Liu H (2019) Reduced graphene oxide incorporated acellular dermal composite scaffold enables efficient local delivery of mesenchymal stem cells for accelerating diabetic wound healing. ACS Biomater Sci Eng 5(8):4054–4066

    Article  CAS  PubMed  Google Scholar 

  • Galkowska H, Wojewodzka U, Olszewski WL (2006) Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial cells in the margin of chronic diabetic foot ulcers. Wound Repair Regen 14(5):558–565

    Article  PubMed  Google Scholar 

  • Geim AK (2009) Graphene: status and prospects. Science 324(5934):1530–1534

    Article  CAS  PubMed  Google Scholar 

  • Geim AK, Novoselov KS (2007) The rise of graphene. Nat Mater 6(3):183–191

    Article  CAS  PubMed  Google Scholar 

  • Goenka S, Sant V, Sant S (2014) Graphene-based nanomaterials for drug delivery and tissue engineering. J Control Release 173(1):75–88

    Article  CAS  PubMed  Google Scholar 

  • Guo F, Kim F, Han TH, Shenoy VB, Huang J, Hurt RH (2011) Hydration-responsive folding and unfolding in graphene oxide liquid crystal phases. ACS Nano 5(10):8019–8025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hong SW, Lee JH, Kang SH, Hwang EY, Hwang Y-S, Lee MH, Han D-W, Park J-C (2014) Enhanced neural cell adhesion and neurite outgrowth on graphene-based biomimetic substrates. Biomed Res Int 2014(1):212149

    PubMed  PubMed Central  Google Scholar 

  • Jakus AE, Shah RN (2017) Multi and mixed 3D-printing of graphene-hydroxyapatite hybrid materials for complex tissue engineering. J Biomed Mater Res A 105(1):274–283

    Article  CAS  PubMed  Google Scholar 

  • Kakran M, Sahoo NG, Bao H, Pan Y, Li L (2011) Functionalized graphene oxide as nanocarrier for loading and delivery of ellagic acid. Curr Med Chem 18(29):4503–4512

    Article  CAS  PubMed  Google Scholar 

  • Kim F, Cote LJ, Huang J (2010a) Graphene oxide: surface activity and two-dimensional assembly. Adv Mater 22(17):1954–1958

    Article  CAS  PubMed  Google Scholar 

  • Kim J, Cote LJ, Kim F, Yuan W, Shull KR, Huang J (2010b) Graphene oxide sheets at interfaces. J Am Chem Soc 132(23):8180–8186

    Article  CAS  PubMed  Google Scholar 

  • Komarcević A (2000) The modern approach to wound treatment. Med Pregl 53(7–8):363–368

    PubMed  Google Scholar 

  • Lakshmanan R, Maulik N (2018) Graphene-based drug delivery systems in tissue engineering and nanomedicine. Can J Physiol Pharmacol 96(9):869–878

    Article  CAS  PubMed  Google Scholar 

  • Lee EJ, Lee JH, Shin YC, Hwang D-G, Kim JS, Jin OS, Jin L, Hong SW, Han D-W (2014) Graphene oxide-decorated PLGA/collagen hybrid fiber sheets for application to tissue engineering scaffolds. Biomater Res 18(1):18–24

    PubMed  PubMed Central  Google Scholar 

  • Lee JH, Shin YC, Jin OS, Kang SH, Hwang Y-S, Park J-C, Hong SW, Han D-W (2015a) Reduced graphene oxide-coated hydroxyapatite composites stimulate spontaneous osteogenic differentiation of human mesenchymal stem cells. Nanoscale 7(27):11642–11651

    Article  CAS  PubMed  Google Scholar 

  • Lee JH, Shin YC, Lee S-M, Jin OS, Kang SH, Hong SW, Jeong C-M, Huh JB, Han D-W (2015b) Enhanced osteogenesis by reduced graphene oxide/hydroxyapatite nanocomposites. Sci Rep 5(1):18833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee H, Paeng K, Kim IS (2018) A review of doping modulation in graphene. Synth Met 244:36–47

    Article  CAS  Google Scholar 

  • Li Y, Liu Y, Fu Y, Wei T, Le Guyader L, Gao G, Liu RS, Chang YZ, Chen C (2012) The triggering of apoptosis in macrophages by pristine graphene through the MAPK and TGF-beta signaling pathways. Biomaterials 33(2):402–411

    Article  PubMed  Google Scholar 

  • Li Z, Wang H, Yang B, Sun Y, Huo R (2015) Three-dimensional graphene foams loaded with bone marrow derived mesenchymal stem cells promote skin wound healing with reduced scarring. Mater Sci Eng C Mater Biol Appl 57:181–188

    Article  CAS  PubMed  Google Scholar 

  • Linares J, Matesanz MC, Vila M, Feito MJ, Gonçalves G, Vallet-Regí M, Marques PA, Portolés MT (2014) Endocytic mechanisms of graphene oxide nanosheets in osteoblasts, hepatocytes and macrophages. ACS Appl Mater Interfaces 6(16):13697–13706

    Article  CAS  PubMed  Google Scholar 

  • Liu N, Luo F, Wu H, Liu Y, Zhang C, Chen J (2008) One-step ionic-liquid-assisted electrochemical synthesis of ionic-liquid-functionalized graphene sheets directly from graphite. Adv Funct Mater 18(10):1518–1525

    Article  CAS  Google Scholar 

  • Lu B, Li T, Zhao H, Li X, Gao C, Zhang S, Xie E (2012) Graphene-based composite materials beneficial to wound healing. Nanoscale 4(9):2978–2982

    Article  CAS  PubMed  Google Scholar 

  • Mahmoudi N, Eslahi N, Mehdipour A, Mohammadi M, Akbari M, Samadikuchaksaraei A, Simchi A (2017) Temporary skin grafts based on hybrid graphene oxide-natural biopolymer nanofibers as effective wound healing substitutes: pre-clinical and pathological studies in animal models. J Mater Sci Mater Med 28(5):73

    Article  CAS  PubMed  Google Scholar 

  • Mohandas A, Anisha BS, Chennazhi KP, Jayakumar R (2015) Chitosan-hyaluronic acid/VEGF loaded fibrin nanoparticles composite sponges for enhancing angiogenesis in wounds. Colloids Surf B Biointerfaces 127:105–113

    Article  CAS  PubMed  Google Scholar 

  • Novoselov KS, Geim AK, Morozov SV, Jiang D, Zhang Y, Dubonos SV, Grigorieva IV, Firsov AA (2004) Electric field effect in atomically thin carbon films. Science 306(5696):666–669

    Article  CAS  PubMed  Google Scholar 

  • Nyambat B, Chen C-H, Wong P-C, Chiang C-W, Satapathy MK, Chuang E-Y (2018) Genipin-crosslinked adipose stem cell derived extracellular matrix-nano graphene oxide composite sponge for skin tissue engineering. J Mater Chem B 6(6):979–990

    Article  CAS  PubMed  Google Scholar 

  • Park S, An J, Jung I, Piner RD, An SJ, Li X, Velamakanni A, Ruoff RS (2009) Colloidal suspensions of highly reduced graphene oxide in a wide variety of organic solvents. Nano Lett 9(4):1593–1597

    Article  CAS  PubMed  Google Scholar 

  • Park J, Kim YS, Ryu S, Kang WS, Park S, Han J, Jeong HC, Hong BH, Ahn Y, Kim B-S (2015) Graphene potentiates the myocardial repair efficacy of mesenchymal stem cells by stimulating the expression of angiogenic growth factors and gap junction protein. Adv Funct Mater 25(17):2590–2600

    Article  CAS  Google Scholar 

  • Patel S, Srivastava S, Singh MR, Singh D (2019) Mechanistic insight into diabetic wounds: pathogenesis, molecular targets and treatment strategies to pace wound healing. Biomed Pharmacother 112:108615

    Article  CAS  PubMed  Google Scholar 

  • Pinto AM, Gonçalves IC, Magalhães FD (2013) Graphene-based materials biocompatibility: a review. Colloids Surf B Biointerfaces 111C:188–202

    Article  Google Scholar 

  • Pumera M (2011) Graphene-based nanomaterials for energy storage. Energy Environ Sci 4(3):668–674

    Article  CAS  Google Scholar 

  • Qiu Z, Kwon AH, Kamiyama Y (2007) Effects of plasma fibronectin on the healing of full-thickness skin wounds in streptozotocin-induced diabetic rats. J Surg Res 138(1):64–70

    Article  CAS  PubMed  Google Scholar 

  • Qiu Y, Wang Z, Owens ACE, Kulaots I, Chen Y, Kane AB, Hurt RH (2014) Antioxidant chemistry of graphene-based materials and its role in oxidation protection technology. Nanoscale 6(20):11744–11755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qu M, Li Y, Wu Q, Xia Y, Wang D (2017) Neuronal ERK signaling in response to graphene oxide in nematode Caenorhabditis elegans. Nanotoxicology 11(4):520–533

    Article  CAS  PubMed  Google Scholar 

  • Raja IS, Kang MS, Kim KS, Jung YJ, Han D-W (2020) Two-dimensional theranostic nanomaterials in cancer treatment: state of the art and perspectives. Cancers 12(6):1657

    Article  CAS  PubMed Central  Google Scholar 

  • Saravanan S, Chawla A, Vairamani M, Sastry TP, Subramanian KS, Selvamurugan N (2017) Scaffolds containing chitosan, gelatin and graphene oxide for bone tissue regeneration in vitro and in vivo. Int J Biol Macromol 104(Pt B):1975–1985

    Article  CAS  PubMed  Google Scholar 

  • Sasidharan A, Panchakarla LS, Chandran P, Menon D, Nair S, Rao CNR, Koyakutty M (2011) Differential nano-bio interactions and toxicity effects of pristine versus functionalized graphene. Nanoscale 3(6):2461–2464

    Article  CAS  PubMed  Google Scholar 

  • Sasidharan A, Panchakarla LS, Sadanandan AR, Ashokan A, Chandran P, Girish CM, Menon D, Nair SV, Rao CN, Koyakutty M (2012) Hemocompatibility and macrophage response of pristine and functionalized graphene. Small 8(8):1251–1263

    Article  CAS  PubMed  Google Scholar 

  • Shahmoradi S, Golzar H, Hashemi M, Mansouri V, Omidi M, Yazdian F, Yadegari A, Tayebi L (2018) Optimizing the nanostructure of graphene oxide/silver/arginine for effective wound healing. Nanotechnology 29(47):475101

    Article  PubMed  Google Scholar 

  • Shahnawaz Khan M, Abdelhamid HN, Wu H-F (2015) Near infrared (NIR) laser mediated surface activation of graphene oxide nanoflakes for efficient antibacterial, antifungal and wound healing treatment. Colloids Surf B Biointerfaces 127:281–291

    Article  CAS  PubMed  Google Scholar 

  • Shams E, Yeganeh H, Naderi-Manesh H, Gharibi R, Mohammad Hassan Z (2017) Polyurethane/siloxane membranes containing graphene oxide nanoplatelets as antimicrobial wound dressings: in vitro and in vivo evaluations. J Mater Sci Mater Med 28(5):75

    Article  PubMed  Google Scholar 

  • Shang NG, Papakonstantinou P, McMullan M, Chu M, Stamboulis A, Potenza A, Dhesi SS, Marchetto H (2008) Catalyst-free efficient growth, orientation and biosensing properties of multilayer graphene nanoflake films with sharp edge planes. Adv Funct Mater 18(21):3506–3514

    Article  CAS  Google Scholar 

  • Shang L, Qi Y, Lu H, Pei H, Li Y, Qu L, Wu Z, Zhang W (2019) 7 – Graphene and graphene oxide for tissue engineering and regeneration. In: Cui W, Zhao X (eds) Theranostic bionanomaterials. Elsevier, Amsterdam, pp 165–185

    Chapter  Google Scholar 

  • Shao Y, Wang J, Wu H, Liu J, Aksay IA, Lin Y (2010) Graphene based electrochemical sensors and biosensors: a review. Electroanalysis 22(10):1027–1036

    Article  CAS  Google Scholar 

  • Sharp A, Clark J (2011) Diabetes and its effects on wound healing. Nurs Stand 25(45):41–47

    Article  PubMed  Google Scholar 

  • Shin SR, Aghaei-Ghareh-Bolagh B, Dang TT, Topkaya SN, Gao X, Yang SY, Jung SM, Oh JH, Dokmeci MR, Tang X, Khademhosseini A (2013) Cell-laden microengineered and mechanically tunable hybrid hydrogels of gelatin and graphene oxide. Adv Mater 25(44):6385–6391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shin YC, Lee JH, Jin L, Kim MJ, Kim Y-J, Hyun JK, Jung T-G, Hong SW, Han D-W (2015) Stimulated myoblast differentiation on graphene oxide-impregnated PLGA-collagen hybrid fibre matrices. J Nanobiotechnol 13(1):21

    Article  Google Scholar 

  • Shin SR, Li Y-C, Jang HL, Khoshakhlagh P, Akbari M, Nasajpour A, Zhang YS, Tamayol A, Khademhosseini A (2016) Graphene-based materials for tissue engineering. Adv Drug Deliv Rev 105(Pt B):255–274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sreenivasulu B, Ramji BR, Nagaral M (2018) A review on graphene reinforced polymer matrix composites. Mater Today Proc 5(1):2419–2428

    Article  CAS  Google Scholar 

  • Takeo M, Lee W, Ito M (2015) Wound healing and skin regeneration. Cold Spring Harb Perspect Med 5(1):a023267

    Article  PubMed  PubMed Central  Google Scholar 

  • Tamayol A, Akbari M, Annabi N, Paul A, Khademhosseini A, Juncker D (2013) Fiber-based tissue engineering: Progress, challenges, and opportunities. Biotechnol Adv 31(5):669–687

    Article  CAS  PubMed  Google Scholar 

  • Tan WS, Arulselvan P, Ng SF, Mat Taib CN, Sarian MN, Fakurazi S (2019) Improvement of diabetic wound healing by topical application of Vicenin-2 hydrocolloid film on Sprague Dawley rats. BMC Complement Altern Med 19(1):20

    Article  PubMed  PubMed Central  Google Scholar 

  • Thangavel P, Kannan R, Ramachandran B, Moorthy G, Suguna L, Muthuvijayan V (2018) Development of reduced graphene oxide (rGO)-isabgol nanocomposite dressings for enhanced vascularization and accelerated wound healing in normal and diabetic rats. J Colloid Interface Sci 517:251–264

    Article  CAS  PubMed  Google Scholar 

  • Thu HE, Zulfakar MH, Ng SF (2012) Alginate based bilayer hydrocolloid films as potential slow-release modern wound dressing. Int J Pharm 434(1–2):375–383

    Article  CAS  PubMed  Google Scholar 

  • Tran TH, Nguyen HT, Pham TT, Choi JY, Choi HG, Yong CS, Kim JO (2015) Development of a graphene oxide nanocarrier for dual-drug chemo-phototherapy to overcome drug resistance in cancer. ACS Appl Mater Interfaces 7(51):28647–28655

    Article  CAS  PubMed  Google Scholar 

  • Weaver CL, Cui XT (2015) Directed neural stem cell differentiation with a functionalized graphene oxide nanocomposite. Adv Healthc Mater 4(9):1408–1416

    Article  CAS  PubMed  Google Scholar 

  • Yang X, Qiu L, Cheng C, Wu Y, Ma Z-F, Li D (2011) Ordered gelation of chemically converted graphene for next-generation electroconductive hydrogel films. Angew Chem Int Ed 50(32):7325–7328

    Article  CAS  Google Scholar 

  • Yang C, Yan Z, Lian Y, Wang J, Zhang K (2020) Graphene oxide coated shell-core structured chitosan/PLLA nanofibrous scaffolds for wound dressing. J Biomaert Sci Polym Ed 31(5):622–641

    Article  CAS  Google Scholar 

  • Zhao H, Ding R, Zhao X, Li Y, Qu L, Pei H, Yildirimer L, Wu Z, Zhang W (2017) Graphene-based nanomaterials for drug and/or gene delivery, bioimaging, and tissue engineering. Drug Discov Today 22(9):1302–1317

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by National Research Foundation of Korea (NRF) funded by the Ministry of Science (NRF-2019R1A4A1024116) and by Korea Environment Industry & Technology Institute (KEITI) through project to develop eco-friendly new materials and processing technology derived from wildlife, funded by Korea Ministry of Environment (MOE) (2021003270006).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dong-Wook Han .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Raja, I.S. et al. (2022). Role of Graphene Family Nanomaterials in Skin Wound Healing and Regeneration. In: Han, DW., Hong, S.W. (eds) Multifaceted Biomedical Applications of Graphene. Advances in Experimental Medicine and Biology, vol 1351. Springer, Singapore. https://doi.org/10.1007/978-981-16-4923-3_5

Download citation

Publish with us

Policies and ethics