Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Efficient synthesis, characterization, and application of biobased scab-bionic hemostatic polymers

Polymer Journal volume 52, pages 615–627 (2020)Cite this article

Subjects

Abstract

Under optimized reaction conditions, by directly using the hemostatic drugs 4-aminomethylbenzoic acid (ABA) and tranexamic acid (TA) as separate comonomers of lactic acid (LA), a series of copolymers, P(LA-co-ABA) and P(LA-co-TA), respectively, with different molar feed ratios were designed and synthesized via melt polycondensation and used as biobased polymeric sustained-release hemostatic materials. Their structure, properties and morphology were systematically investigated by Fourier transform infrared spectrometer (FTIR), proton nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), X-ray diffraction (XRD), differential scanning calorimetery (DSC), thermogravimetric (TG), scanning electron microscopy (SEM), water contact angle and degradation tests. The degradation rate within 7 weeks can reach 77%. When the molar feed ratios of ABA and TA are 20% and 10%, respectively, the corresponding copolymers have relatively lower crystallinity and smaller water contact angle and exhibit the best coagulation performance. In addition, these powdery copolymers have good application convenience, can form a degradable protective membrane similar to a blood scab on the wound surface and continuously exert hemostatic effects to promote wound healing, as anticipated.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Scheme 1
Scheme 2
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Scheme 3
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Saporito F, Sandri G, Rossi S, Bonferoni MC, Riva F, Malavasi L, et al. Freeze dried chitosan acetate dressings with glycosaminoglycans and traxenamic acid. Carbohyd Polym. 2018;184:408–17.

    Article  CAS  Google Scholar 

  2. Li WF, Gao FY, Kan JL, Deng J, Wang BC, Hao SL. Synthesis and fabrication of a keratin-conjugated insulin hydrogel for the enhancement of wound healing. Colloids Surf B. 2019;175:436–44.

    Article  CAS  Google Scholar 

  3. Zhang ZY, Kuang GZ, Zong S, Liu S, Xiao HH, Chen XS, et al. Sandwich-like fibers/sponge composite combining chemotherapy and hemostasis for efficient postoperative prevention of tumor recurrence and metastasis. Adv Mater. 2018;30:1803217.

    Article  CAS  Google Scholar 

  4. Heher P, Mühleder S, Mittermayr R, Redl H, Slezak P. Fibrin-based delivery strategies for acute and chronic wound healing. Adv Drug Deliv Rev. 2018;129:134–47.

    Article  CAS  PubMed  Google Scholar 

  5. Sundaram MN, Kaliannagounder VK, Selvaprithiviraj V, Suresh MK, Biswas R, Vasudevan AK, et al. Bioadhesive, hemostatic, and antibacterial in situ chitin-fibrin nanocomposite gel for controlling bleeding and preventing infections at mediastinum. ACS Sustain Chem Eng. 2018;6:7826–40.

    Article  CAS  Google Scholar 

  6. Sezer UA, Kocer Z, Sahin I, Aru B, Demirel GY, Sezer S. Oxidized regenerated cellulose cross-linked gelatin microparticles for rapid and biocompatible hemostasis—a versatile cross-linking agent. Carbohyd Polym. 2018;200:624–32.

    Article  CAS  Google Scholar 

  7. Hu Z, Lu ST, Cheng Y, Kong SZ, Li SD, Li CP, et al. Investigation of the effects of molecular parameters on the hemostatic properties of chitosan. Molecules. 2018;23:3147.

    Article  PubMed Central  CAS  Google Scholar 

  8. Najar MH, Minaiyan M, Taheri AJ. Preparation and in vivo evaluation of a novel gel-based wound dressing using arginine-alginate surface-modified chitosan nanofibers. Biomater Appl. 2018;32:689–701.

    Article  CAS  Google Scholar 

  9. Tong ZR, Chen Y, Liu Y, Tong L, Chu JM, Xiao KC, et al. Preparation, characterization and properties of alginate/poly(gamma-glutamic acid) composite microparticles. Mar Drugs. 2017;15:91.

    Article  PubMed Central  CAS  Google Scholar 

  10. Sanandiya ND, Lee S, Rho S, Lee H, Kim IS, Hwang DS. Tunichrome-inspired pyrogallol functionalized chitosan for tissue adhesion and hemostasis. Carbohyd Polym. 2019;208:77–85.

    Article  CAS  Google Scholar 

  11. Zhao X, Wu H, Guo BL, Dong RN, Qiu YS, Ma PX. Antibacterial anti-oxidant electroactive injectable hydrogel as self-healing wound dressing with hemostasis and adhesiveness for cutaneous wound healing. Biomaterials. 2017;122:34–47.

    Article  CAS  PubMed  Google Scholar 

  12. Zhu J, Li FX, Wang XL, Yu JY, Wu DQ. Hyaluronic acid and polyethylene glycol hybrid hydrogel encapsulating nanogel with hemostasis and sustainable antibacterial property for wound healing. ACS Appl Mater Interfaces. 2018;10:13304–16.

    Article  CAS  PubMed  Google Scholar 

  13. Lokhande G, Carrow JK, Thakur T, Xavier JR, Parani M, Bayless KJ, et al. Nanoengineered injectable hydrogels for wound healing application. Acta Biomater. 2018;70:35–47.

    Article  CAS  PubMed  Google Scholar 

  14. Catanzano O, D’Esposito V, Formisano P, Boateng JS, Quaglia F. Composite alginate-hyaluronan sponges for the delivery of tranexamic acid in postextractive alveolar wounds. J Pharm Sci. 2018;107:654–61.

    Article  CAS  PubMed  Google Scholar 

  15. Jhiang J-S, Wu T-H, Chou C-J, Chang Y, Huang C-J. Gel-like ionic complexes for antimicrobial, hemostatic and adhesive properties. J Mater Chem B. 2019;7:2878–87.

    Article  CAS  PubMed  Google Scholar 

  16. Chen L, Cheng H-H, Xiong J, Zhu Y-T, Zhang H-P, Xiong X, et al. Improved mechanical properties of poly(butylene succinate) membrane by co-electrospinning with gelatin. Chin J Polym Sci. 2018;36:1063–9.

    Article  CAS  Google Scholar 

  17. Wang YF, Yin ML, Li ZG, Liu Y, Ren XH, Huang T-S. Preparation of antimicrobial and hemostatic cotton with modified mesoporous particles for biomedical applications. Colloids Surf B. 2018;165:199–206.

    Article  CAS  Google Scholar 

  18. Huang H, Liu HH, Zhou H, Liang ZL, Song DD, Zhang Y, et al. Drug-release system of microchannel transport used in minimally invasive surgery for hemostasis. Drug Des Dev Ther. 2019;13:881–96.

    Article  CAS  Google Scholar 

  19. Zhu YQ, Romain C, Williams CK. Sustainable polymers from renewable resources. Nature. 2016;540:354–62.

    Article  CAS  PubMed  Google Scholar 

  20. Hador R, Botta A, Venditto V, Lipstman S, Goldberg I, Kol M. The dual-stereocontrol mechanism: heteroselective polymerization of rac-lactide and syndioselective polymerization of meso-lactide by chiral aluminum salan catalysts. Angew Chem Int Ed. 2019;58:14679–85.

    Article  CAS  Google Scholar 

  21. Qi M, Dong Q, Wang DW, Byers JA. Electrochemically switchable ring-opening polymerization of lactide and cyclohexene oxide. J Am Chem Soc. 2018;140:5686–90.

    Article  CAS  PubMed  Google Scholar 

  22. Marin P, Tschan MJ-L, Isnard F, Robert C, Haquette P, Trivelli X, et al. Polymerization of rac-lactide using achiral iron complexes: access to thermally stable stereocomplexes. Angew Chem Int Ed. 2019;58:12585–9.

    Article  CAS  Google Scholar 

  23. Ladelta V, Zapsas G, Abou-hamad E, Gnanou Y, Hadjichristidis N. Tetracrystalline tetrablock quarterpolymers: four different crystallites under the same roof. Angew Chem Int Ed. 2019;58:16267–74.

    Article  CAS  Google Scholar 

  24. He YX, Eloi J-C, Harniman RL, Richardson RM, Whittell GR, Mathers RT, et al. Uniform biodegradable fiber-like micelles and block comicelles via “living” crystallization-driven self-assembly of poly(L-lactide) block copolymers: the importance of reducing unimer self-nucleation via hydrogen bond disruption. J Am Chem Soc. 2019;141:19088–98.

    Article  CAS  PubMed  Google Scholar 

  25. Xiong ZQ, Zhang Y, Du XY, Song PA, Fang ZP. Green and scalable fabrication of core-shell biobased flame retardants for reducing flammability of polylactic acid. ACS Sustain Chem Eng. 2019;7:8954–63.

    Article  CAS  Google Scholar 

  26. Sun JH, Li L, Li J. Effects of furan-phosphamide derivative on flame retardancy and crystallization behaviors of poly(lactic acid). Chem Eng J. 2019;369:150–60.

    Article  CAS  Google Scholar 

  27. Kim YJ, Kim JS, Lee SY, Mahajan RL, Kim YT. Exploration of hybrid nanocarbon composite with polylactic acid for packaging applications. Int J Biol Sci. 2020;144:135–42.

    CAS  Google Scholar 

  28. Yang FH, Niu XF, Gu XN, Xu CP, Wang W, Fan YB. Biodegradable magnesium-incorporated poly(L-lactic acid) micro-spheres for manipulation of drug release and alleviation of inflammatory response. ACS Appl Mater Interfaces. 2019;11:23546–57.

    Article  CAS  PubMed  Google Scholar 

  29. Nofar M, Sacligil D, Carreau PJ, Kamal MR, Heuzey MC. Poly (lactic acid) blends: processing, properties and applications. Int J Biol Macromol. 2019;125:307–60.

    Article  CAS  PubMed  Google Scholar 

  30. Munim SA, Raza ZA. Poly(lactic acid) based hydrogels: formation, characteristics and biomedical applications. J Porous Mater. 2019;26:881–901.

    Article  CAS  Google Scholar 

  31. Kang B-K, Kim MM, Jun DW, Park J, Jeong J, Sohn JH, et al. Stem cell treatment on acute liver failure model using semipermeable poly lactic-co-glycolic acid membrane pouch. J Hepatol. 2019;70:E422.

  32. Shin HM, Ju Y, Kim G, Lee JW, Seo MW, Sim JH, et al. Recyclable cytokines on short and injectable polylactic acid fibers for enhancing T-cell function. Adv Funct Mater. 2019;29:1808361.

    Article  CAS  Google Scholar 

  33. Zhang JF, Chen GJ, Bhat GS, Azari H, Pen HL. Electret characteristics of melt-blown polylactic acid fabrics for air filtration application. J Appl Polym Sci. 2020;137:48309.

    Article  CAS  Google Scholar 

  34. Luo S-H, Wu Y-C, Cao L, Wang Q-F, Chen S-X, Hao Z-F, et al. One-pot preparation of polylactic acid-ibuprofen conjugates and their performance characterization. Polym Chem. 2017;8:7009–16.

    Article  CAS  Google Scholar 

  35. Luo S-H, Wu Y-C, Cao L, Lin J-Y, Gao J, Chen S-X, et al. Direct metal-free preparation of functionalizable polylactic acid-ethisterone conjugates in a one-pot approach. Macromol Chem Phys. 2019;220:1800475.

    Article  CAS  Google Scholar 

  36. Lu DD, Duan PX, Liu T, Li J, Li TE, Lei ZQ. Synthesis and characterization of biodegradable linear-hyperbranched barbell-like poly(ethylene glycol)-supported poly(lactic-ran-glycolic acid) copolymers through direct polycondensation. Polym Int. 2014;63:244–51.

    Article  CAS  Google Scholar 

  37. Shi DJ, Hua JT, Zhang L, Chen MQ. Synthesis of bio-based poly(lactic acid-co-10-hydroxy decanoate) copolymers with high thermal stability and ductility. Polymers. 2015;7:468–83.

    Article  CAS  Google Scholar 

  38. Li XY, Li Y-C, Chen MJ, Shi QS, Sun RC, Wang XY. Chitosan/rectorite nanocomposite with injectable functionality for skin hemostasis. J Mater Chem B. 2018;6:6544–9.

    Article  CAS  PubMed  Google Scholar 

  39. Tsuji H, Kikkawa K, Arakawa Y. Cocrystallization of monomer units of biobased and biodegradable poly(L-lactic acid-co-glycolic acid) random copolymers. Polym J. 2018;50:1079–88.

    Article  CAS  Google Scholar 

  40. Takenaka M, Kimura Y, Ohara H. Molecular weight increase driven by evolution of crystal structure in the process of solid-state polycondensation of poly(L-lactic acid). Polymer. 2017;126:133–40.

    Article  CAS  Google Scholar 

  41. Abu Ghalia M, Dahman YJ. Biodegradable poly(lactic acid)-based scaffolds: Synthesis and biomedical applications. J Polym Res. 2017;24:74.

    Article  CAS  Google Scholar 

  42. Marques DS, Gil MH. Baptista CMSG. Improving lactic acid melt polycondensation: The role of co-catalyst. J Appl Polym Sci. 2013;128:2145–51.

    CAS  Google Scholar 

  43. Huang W, Cheng N, Qi YB, Zhang TR, Jiang W, Li H, et al. Synthesis of high molecular weight poly(L-lactic acid) and poly(D-lactic acid) with improved thermal stability via melt/solid polycondensation catalyzed by biogenic creatinine. Polymer. 2014;55:1491–6.

    Article  CAS  Google Scholar 

  44. Ge YP, Yuan D, Luo ZL, Wang BB. Synthesis and characterization of poly(ester amide) from renewable resources through melt polycondensation. Express Polym Lett. 2014;8:50–54.

    Article  CAS  Google Scholar 

  45. Jihen M, Slim S, Christelle D, Souhir A, Rachid EG. Random poly(lactic acid-co-β-alanine): synthesis and characterizations. J Macromol Sci A. 2015;52:1002–8.

    Article  CAS  Google Scholar 

  46. Zhao XP, Ding Z, Zhang YJ, Wang YX, Peng SX. Preparation and crystallization kinetics of polyesteramide based on poly(l-lactic acid). e-Polymers. 2018;18:97–104.

    Article  CAS  Google Scholar 

  47. Ye R-R, Wang Z-Y, Luo S-H, Yang L-T, Xiao X. Synthesis and characterization of the biomaterial poly(lactic acid-co-Nε-carbo-benzoyloxy-L-lysine) via direct melt copolymerization. J Appl Polym Sci. 2011;121:420–6.

    Article  CAS  Google Scholar 

  48. Ye R-R, Wang Z-Y, Yang K, Luo S-H. Synthesis and character-ization of a novel biodegradable material, poly(lactic acid-co-tryptophane). Des Monomers Polym. 2010;13:415–26.

    Article  CAS  Google Scholar 

  49. Wang Z-Y, Hou X-N, Mao Z-Z, Ye R-R, Mo Y-Q, Finlow DE. Synthesis and characterization of biodegradable poly(lactic acid-co-glycine) via direct melt copolymerization. Iran Polym J. 2008;17:791–8.

    CAS  Google Scholar 

  50. Zhao Y-M, Wang Z-Y, Yang F. Characterization of poly(D,L-lactic acid) synthesized by direct melt polymerization and its application in Chinese traditional medicine compound prescription microspheres. J Appl Polym Sci. 2005;97:195–200.

    Article  CAS  Google Scholar 

  51. Xiong CD, Cheng LM, Xu RP, Deng XM. Studies on the copolymerization of D,L-lactide with poly(tetramethylene ether glyeol). Funct Polym. 1991;4:133–8.

    CAS  Google Scholar 

  52. Wang Z-Y, Zhao H-J, Wang Q-F, Ye R-R, Finlow DE. Biodegradable aliphatic/aromatic copolyesters based on terephthalic acid and poly(L-lactic acid): synthesis, characterization and hydrolytic degradation. J Appl Polym Sci. 2010;117:1405–15.

    CAS  Google Scholar 

  53. Xiong J-F, Luo S-H, Wang Q-F, Wang Z-Y, Qi J. Synthesis and characterization of a novel flame retardant, poly(lactic acid-co-3,3’-diaminobenzidine). Des Monomers Polym. 2013;16:389–97.

    Article  CAS  Google Scholar 

  54. Perumal G, Pappuru S, Chakraborty D, Nandkumar AM, Chand DK, Doble M. Synthesis and characterization of curcumin loaded PLA-hyperbranched polyglycerol electrospun blend for wound dressing applications. Mater Sci Eng C. 2017;76:1196–204.

    Article  CAS  Google Scholar 

  55. Hickman DA, Pawlowski CL, Sekhon UDS, Marks J, Sen Gupta A. Biomaterials and advanced technologies for hemostatic management of bleeding. Adv Mater. 2018;30:1700859.

    Article  CAS  Google Scholar 

  56. Sara P, Nahrizul AK, Ehsan Z, Mark RT. Well-ordered mesoporous silica and bioactive glasses: Promise for improved hemostasis. Biomater Sci. 2019;7:31–50.

    Article  Google Scholar 

  57. Zhang SH, Li JW, Chen SJ, Zhang XY, Ma JW, He JM. Oxidized cellulose-based hemostatic materials. Carbohyd Polym. 2020;230:115585.

    Article  CAS  Google Scholar 

  58. Luo YF, Wang YL, Niu XF, Fu CH, Wang SJ. Synthesis, characterization and biodegradation of butanediamine-grafted poly(D, L-lactic acid). Eur Polym J. 2007;43:3856–64.

    Article  CAS  Google Scholar 

  59. Bolliger D, Tanaka KA. Tranexamic acid in vascular surgery: antifibrinolytic or clot-stabilising activity. Br J Anaesth. 2020;124:4–6.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by the Science and Technology Program of Guangzhou (No. 201607010301), the Open Fund of the Key Laboratory of Functional Molecular Engineering of Guangdong Province in SCUT (No. 2017kf01), the National Natural Science Foundation of China (20772035), and the Guangdong Provincial Science and Technology Project (No. 2017A010103016).

Author information

Authors and Affiliations

  1. School of Chemistry, South China Normal University, Key Laboratory of Theoretical Chemistry of Environment, Ministry of Education, Guangzhou Key Laboratory of Analytical Chemistry for Biomedicine, Guangzhou, 510006, PR China

    Jian-Yun Lin, Shi-He Luo, Si-Hong Chen, Li-Ting Yang, Ying Xiao, Zhao-Hao Huang & Zhao-Yang Wang

  2. Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, 381 Wushan Road, Guangzhou, 510640, PR China

    Shi-He Luo & Zhao-Yang Wang

Authors
  1. Jian-Yun Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shi-He Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Si-Hong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Li-Ting Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhao-Hao Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhao-Yang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Shi-He Luo, Li-Ting Yang or Zhao-Yang Wang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, JY., Luo, SH., Chen, SH. et al. Efficient synthesis, characterization, and application of biobased scab-bionic hemostatic polymers. Polym J 52, 615–627 (2020). https://doi.org/10.1038/s41428-020-0315-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41428-020-0315-z

This article is cited by

Search

Advanced search

Quick links