An easy-to-use wound dressing gelatin-bioactive nanoparticle gel and its preliminary in vivo study

  • Chen Wang
  • Feiyan Zhu
  • Yang Cui
  • Huihui Ren
  • Yue Xie
  • Ailing Li
  • Lijun Ji
  • Xiaozhong QuEmail author
  • Dong QiuEmail author
  • Zhenzhong YangEmail author
Clinical Applications of Biomaterials Original Research
Part of the following topical collections:
  1. Clinical Applications of Biomaterials


Beyond promoting hard tissue repairing, bioactive glasses (BGs) have also been proved to be beneficial for wound healing. Nano-scale BGs prepared by sol-gel method were found to have a better performance as they have a larger specific surface area. In this work, bioactive nanoparticles (nBPs) with mean diameter of 12 nm (BP-12) instead of conventional BGs were mixed with gelatin to form an easy-to-use hydrogel as a dressing for skin wound. It was found that the composite of BP-12 and gelatin could form a hydrogel (BP-12/Gel) under 25 °C, which showed pronounced thixotropy at a practically accessible shear rate, therefore become easy to be used for wound cover. In vitro, the composite hydrogel of BP-12 and gelatin had good biocompatibility with the fibroblast cells. In vivo, rapid cutaneous-tissue regeneration and tissue-structure formation within 7 days was observed in the wound-healing experiment performed in rats. This hydrogel is thus a promising easy-to-use wound dressing material.

Graphical Abstract

Open image in new window


Gelatin Wound Closure Bioactive Glass Composite Hydrogel Fibroblast L929 Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by MOST (Project No. 2012CB933200, 2013DFG52300) and NSFC (Project No. 21474122, 51173193, 81202931).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


  1. 1.
    Balasubramani M, Kumar TR, Babu M. Skin substitutes: a review. Burns. 2001;27:534–44.CrossRefGoogle Scholar
  2. 2.
    Ojeh N, Pastar I, Tomic-Canic M, Stojadinovic O. Stem cells in skin regeneration, wound healing, and their clinical applications. Int J Mol Sci. 2015;16:25476–501.CrossRefGoogle Scholar
  3. 3.
    Reimers K, Liebsch C, Radtke C, Kuhbier JW, Vogt PM. Silks as scaffolds for skin reconstruction. Biotechnol Bioeng. 2015;112:2201–5.CrossRefGoogle Scholar
  4. 4.
    Sen CK, Gordillo GM, Roy S, Kirsner R, Lambert L, Hunt TK, Gottrup F, Gurtner GC, Longaker MT. Human skin wounds: a major and snowballing threat to public health and the economy. Wound Repair Regen. 2009;17:763–71.CrossRefGoogle Scholar
  5. 5.
    Peck MD. Epidemiology of burns throughout the world. Part I: distribution and risk factors. Burns. 2011;37:1087–100.CrossRefGoogle Scholar
  6. 6.
    Miguez-Pacheco V, Hench LL, Boccaccini AR. Bioactive glasses beyond bone and teeth: emerging applications in contact with soft tissues. Acta Biomater. 2015;13:1–15.CrossRefGoogle Scholar
  7. 7.
    Pereira RF, Barrias CC, Granja PL, Bartolo PJ. Advanced biofabrication strategies for skin regeneration and repair. Nanomedicine. 2013;8:603–21.CrossRefGoogle Scholar
  8. 8.
    Sun BK, Siprashvili Z, Khavari PA. Advances in skin grafting and treatment of cutaneous wounds. Science. 2014;346:941–5.CrossRefGoogle Scholar
  9. 9.
    Hench LL. Bioceramics. J Am Ceram Soc. 1998;81:1705–28.CrossRefGoogle Scholar
  10. 10.
    Livingston T, Ducheyne P, Garino J. In vivo evaluation of a bioactive scaffold for bone tissue engineering. J Biomed Mater Res. 2002;62:1–13.CrossRefGoogle Scholar
  11. 11.
    Rahaman MN, Day DE, Bal BS, Fu Q, Jung SB, Bonewald LF, Tomsia AP. Bioactive glass in tissue engineering. Acta Biomater. 2011;7:2355–73.CrossRefGoogle Scholar
  12. 12.
    Ostomel TA, Shi Q, Tsung CK, Liang H, Stucky GD. Spherical bioactive glass with enhanced rates of hydroxyapatite deposition and hemostatic activity. Small. 2006;2:1261–5.CrossRefGoogle Scholar
  13. 13.
    Ostomel TA, Shi Q, Stucky GD. Oxide hemostatic activity. J Am Chem Soc. 2006;128:8384–5.CrossRefGoogle Scholar
  14. 14.
    Roether JA, Boccaccini AR, Hench LL, Maquet V, Gautier S, Jerome R. Development and in-vitro characterisation of novel bioresorbable and bioactive composite materials based on polylactide foams and Bioglass (R) for tissue engineering applications. Biomaterials. 2002;23:3871–8.CrossRefGoogle Scholar
  15. 15.
    Day RM, Boccaccini AR, Shurey S, Roether JA, Forbes A, Hench LL, Gabe SM. Assessment of poly(glycolic acid) mesh and bioactive glass for soft tissue engineering scaffolds. Biomaterials. 2004;25:5857–66.CrossRefGoogle Scholar
  16. 16.
    Gorustovich AA, Perio C, Roether JA, Boccaccini AR. Effect of bioactive glasses on angiogenesis: a review of in vitro and in vivo evidence. Tissue Eng B. 2010;16:199–207.CrossRefGoogle Scholar
  17. 17.
    Balakrishnan B, Mohanty M, Fernandez AC, Mohanan PV, Jayakrishnan A. Evaluation of the effect of incorporation of dibutyryl cyclic adenosine monophosphate in an in situ-forming hydrogel wound dressing based on oxidized alginate and gelatin. Biomaterials. 2006;2:1355–61.CrossRefGoogle Scholar
  18. 18.
    Tran NQ, Joung YK, Lih E, Park KD. In Situ forming and rutin-releasing chitosan hydrogels as injectable dressings for dermal wound healing. Biomacromolecules. 2011;12:2872–80.CrossRefGoogle Scholar
  19. 19.
    Le Meins JF, Moldenaers P, Mewis J. Suspensions in polymer melts. 1. Effect of particle size on the shear flow behavior. Ind Eng Chem Res. 2002;41:6297–304.CrossRefGoogle Scholar
  20. 20.
    Montes S, White JL. Rheological models of rubber-carbon black compounds: low interaction viscoelastic models and high interaction thixotropic - plastic - viscoelastic models. J Non-Newton Fluid Mech. 1993;49:277–98.CrossRefGoogle Scholar
  21. 21.
    Letwimolnun W, Vergnes B, Ausias G, Carreau PJ. Stress overshoots of organoclay nanocomposites in transient shear flow. J Non-Newton Fluid Mech. 2007;141:167–79.CrossRefGoogle Scholar
  22. 22.
    Mewis J, Wagner NJ. Thixotropy. Adv Colloid Interface Sci. 2009;147–148:214–27.CrossRefGoogle Scholar
  23. 23.
    Guigo N, Sbirrazzuoli N, Vyazovkin S. Gelation on heating of supercooled gelatin solutions. Macromol Rapid Commun. 2012;33:698–702.CrossRefGoogle Scholar
  24. 24.
    Crescenzi V, Francescangeli A, Taglienti A. New gelatin-based hydrogels via enzymatic networking. Biomacromolecules. 2002;3:1384–91.CrossRefGoogle Scholar
  25. 25.
    Wang Y, Guo M, Genga Z, Xua H, Wang X, Guo X. Simple approach to generate fluorescent quantum dots/gelatin composite with thermo-responsive and reversible sol-gel transition. Soft Mater. 2015;13:177–82.Google Scholar
  26. 26.
    Vlierberghe SV, Schacht E, Dubruel P. Reversible gelatin-based hydrogels: fine tuning of material properties. Eur Polym J. 2011;47:1039–47.CrossRefGoogle Scholar
  27. 27.
    Lei B, Shin KH, Noh DY, Jo IH, Koh YH, Choi WY, Kim HE. Nanofibrous gelatin-silica hybrid scaffolds mimicking the native extracellular matrix (ECM) using thermally induced phase separation. J Mater Chem. 2012;22:14133–40.CrossRefGoogle Scholar
  28. 28.
    Kim HW, Song JH, Kim HE. Nanofiber generation of gelatin-hydroxyapatite biomimetics for guided tissue regeneration. Adv Funct Mater. 2005;15:1988–94.CrossRefGoogle Scholar
  29. 29.
    Jenkins HP, Clarke JS. Gelatin sponge, a new hemostatic substance-studies on absorbability. Arch Surg. 1945;51:253–61.CrossRefGoogle Scholar
  30. 30.
    Hu G, Xiao L, Tong P, Bi D, Wang H, Ma H, Zhu G, Liu H. Antibacterial hemostatic dressings with nanoporous bioglass containing silver. Int J Nanomed. 2012;7:2613–20.CrossRefGoogle Scholar
  31. 31.
    Lin C, Mao C, Zhang J, Li Y, Chen X. Healing effect of bioactive glass ointment on full-thickness skin wounds. Biomed Mater. 2012;7:045017.CrossRefGoogle Scholar
  32. 32.
    Curtis AR, West NX, Su B. Synthesis of nanobioglass and formation of apatite rods to occlude exposed dentine tubules and eliminate hypersensitivity. Acta Biomater. 2010;6:3740–6.CrossRefGoogle Scholar
  33. 33.
    Lin S, Ionescu C, Pike KJ, Smith ME, Jones JR. Nanostructure evolution and calcium distribution in sol-gel derived bioactive glass. J Mater Chem. 2009;19:1276–82.CrossRefGoogle Scholar
  34. 34.
    Hong Z, Liu A, Chen L, Chen X, Jing X. Mono-dispersed bioactive glass nanospheres: preparation and effects on biomechanics of mammalian cells. J Non-Cryst Solids. 2009;355:368–72.CrossRefGoogle Scholar
  35. 35.
    Wang C, Xie Y, Li A, Shen H, Wu D, Qiu D. Bioactive nanoparticle through post-modification of colloidal silica. ACS Appl Mater Interfaces. 2014;6:4935–9.CrossRefGoogle Scholar
  36. 36.
    Wang C, Shen H, Tian Y, Xie Y, Li A, Ji L, Niu Z, Wu D, Qiu D. Bioactive nanoparticle-gelatin composite scaffold with mechanical performance comparable to cancellous bones. ACS Appl Mater Interfaces. 2014;6:13061–8.CrossRefGoogle Scholar
  37. 37.
    Jiao G, He X, Li X, Qiu J, Xu H, Zhang N, Liu S. Limitations of MTT and CCK-8 assay for evaluation of graphene cytotoxicity. RSC Adv. 2015;5:53240–4.CrossRefGoogle Scholar
  38. 38.
    Pereira R, Carvalho A, Vaz DC, Gil MH, Mendes A, Bártolo P. Development of novel alginate based hydrogel films for wound healing applications. Int J Biol Macromol. 2013;52:221–30.CrossRefGoogle Scholar
  39. 39.
    Dias AM, Braga MEM, Seabra IJ, Ferreira P, Gil MH, de Sousa HC. Development of natural-based wound dressings impregnated with bioactive compounds and using supercritical carbon dioxide. Int J Pharm. 2011;408:9–19.CrossRefGoogle Scholar
  40. 40.
    Yannas IV, Burke JF. Design of an artificial skin. I. Basic design principles. J Biomed Mater Res. 1980;14:65–81.CrossRefGoogle Scholar
  41. 41.
    Abdelrahman T, Newton H. Wound dressings: principles and practice. Surgery. 2011;29:491–5.Google Scholar
  42. 42.
    Burke JF, Yannas IV, Quinby WC Jr, Bondoc CC, Jung WK. Successful use of a physiologically acceptable artificial skin in the treatment of extensive burn injury. Ann Surg. 1981;194:413–28.CrossRefGoogle Scholar
  43. 43.
    Kumbar SG, Nukavarapu SP, James R, Nair LS, Laurencin CT. Electrospun poly(lactic acid-co-glycolic acid) scaffolds for skin tissue engineering. Biomaterials. 2008;29:4100–7.CrossRefGoogle Scholar
  44. 44.
    Eaglstein WH. Moist wound healing with occlusive dressings: a clinical focus. Dermatol Surg. 2011;27:175–81.Google Scholar
  45. 45.
    Greaves NS, Iqbal SA, Baguneid M, Bayat A. The role of skin substitutes in the management of chronic cutaneous wounds. Wound Rep Reg. 2013;21:194–210.CrossRefGoogle Scholar
  46. 46.
    Geoffrey CG, Sabine W, Yann B, Michael TL. Wound repair and regeneration. Nature. 2008;453:314–21.CrossRefGoogle Scholar
  47. 47.
    Jones JR. Review of bioactive glass: from Hench to hybrids. Acta Biomater. 2013;9:4457–86.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of ChemistryChinese Academy of SciencesBeijingChina
  2. 2.University of Chinese Academy of SciencesBeijingChina
  3. 3.College of Chemistry and Chemical EngineeringYangzhou UniversityYangzhouChina

Personalised recommendations