Article
  • Moisture Wound Healing Characteristics of Alginate Sponge and Hydrogel
  • Ga Young Park, Jeong Hyun Yeum, Dong Joon Yang*, Guen Oh Park*, Yun Hee Kim**, Saewha Jeon**, Tae Jung Kim***, Eun Jung Oh***, Ho Yun Chung***, and Jin Hyun Choi

  • Department of Bio-fibers and Materials Science, Kyungpook National University, Daegu 41566, Korea
    *Megagen Implant, Gyeongsangbuk-do 38552, Korea
    **Tego Science, Seoul 08505, Korea
    ***Department of Plastic Surgery, Kyungpook National University Hospital, Daegu 41944, Korea

  • 알지네이트 스폰지 및 하이드로젤의 습윤성 창상치유 특성
  • 박가영 · 염정현 · 양동준* · 박근오* · 김윤희** · 전세화** · 김태정*** · 오은정*** · 정호윤*** · 최진현

  • 경북대학교 바이오섬유소재학과, *(주)메가젠임플란트, **(주)테고사이언스, ***경북대학교병원 성형외과

Abstract

Alginate sponge and hydrogel were prepared by a drying/crosslinking method and their wound healing characteristics were investigated comparatively. The alginate hydrogel had a higher equilibrium water content than the sponge, providing a moist wound healing condition without absorbing exudate from a wound. The amounts of proinflammatory cytokines released by macrophages were lowered due to the cytokine-binding effects of the alginate sponge and hydrogel. The hydrogel lowered the cytokine level more dominantly than the sponge, suggesting that the affinity of alginate molecules to cytokines increases at a more swollen state. The hydrogel allowed superior wound healing and contraction at the early stage of application. However, epithelialization was conspicuous when the sponge was applied. It was confirmed through histological examination and RNA expression analysis that angiogenesis, formation of collagen fibers, regeneration of epithelium, and production of protein were promoted using the alginate sponge and hydrogel as wound dressing materials.


건조/가교법으로 제조한 알지네이트 스폰지 및 하이드로젤의 물리적, 생물학적 특성 및 창상치유 특성을 고찰하였다. 하이드로젤은 스폰지 대비 높은 평형 함수율을 보유하였고, 자체적으로 수분을 함유하고 있기 때문에 상대적으로 우수한 습윤 창상치유 환경을 제공할 수 있었다. 알지네이트 스폰지 및 하이드로젤의 사이토카인 결속효과에 기인하여 대식세포로부터 분비되는 전염증성 사이토카인의 함량이 감소됨을 확인하였으며, 특히 하이드로젤의 사이토카인 억제효과가 더욱 두드러지게 나타났는데, 이는 보다 팽윤된 상태에서 알지네이트 분자의 사이토카인에 대한 결속력이 증가함을 의미한다. 창상형성 초기 하이드로젤에 의한 창상치유 및 수축 효과가 스폰지에 비해 우수한 것으로 나타났으나, 상피화는 스폰지를 적용했을 때 보다 우세하게 진행되었다. 조직학적 평가와 RNA 발현 분석으로부터 알지네이트 스폰지 및 하이드로젤은 혈관 및 콜라겐 섬유의 형성, 상피조직의 재생 및 단백질의 생성등을 촉진함을 확인하였다.


Keywords: alginate, sponge, hydrogel, cytokine, wound healing

Introduction

A large number of dressings are currently used in the management of burns, split graft donor sites, chronic ulcers, and so on.1,2 There are two kinds of dressings; dry type and wet type. It has been reported that wounds reepithelialize more rapidly under moist conditions than under dry ones and the rate of dermal repair increases under moist conditions.3,4
Sodium alginate, a linear copolymer of 1,4-linked β-D-mannuronate (M) and α-D-guluronate (G) residues, is isolated from marine algae and well dissolved in water due to negatively charged carbonyl group. Alginate is widely used in industry and medicine for many applications such as scaffolds and wound dressings due to low toxicity, favorable mechanical properties, and capacity for bioresorption of the constituent materials.5-8 Alginate dressings are widely used in the treatment of exuding wounds. Alginate maintains a physiologically moist micro environment that promotes healing and the formation of granulation tissue. Alginate can be rinsed away by saline irrigation, thus the removal of the dressing does not interfere with healing granulation tissue. This makes dressing changes virtually painless. Alginate non-woven fabrics are clinically applied for moisture wound healing.
Several types of moist wound dressings are developed for application to variety of wounds. Films, foams, hydrocolloids, hydrogels, and hydrofibers are typical moist wound dressings. Each has different physical property and biological contribution for wound healing. Highly water-soluble sodium alginate is crosslinked with multivalent metal cations, mostly Ca2+ ions to produce insoluble calcium alginate in the forms of hydrogels, sponges, sheets, beads, and non-woven fabrics. Though alginate non-woven fabrics were widely and clinically commercialized, they have the current concerns with cytotoxicity and the foreign-body reactions caused by dressing debris.9
In this study, the alginate sponge and hydrogel were prepared by a drying/crosslinking method and their physical and biological characteristics including equilibrium water content, cytotoxicity, and proinflammatory cytokine level were evaluated. Finally, comparative study on the wound healing effects of each dressing was carried out with an animal model.

References
  • 1. M. Dyson, S. R. Young, L. Pendle, D. F. Webster, and S. Lang, J. Invest. Dertol., 91, 434 (1991).
  •  
  • 2. Y. Suzuki, M. Tanihara, Y. Nishmura, K. Suzuki, Y. Kakimura, and Y. Shimizu, ASAIO J., 43, 854 (1997).
  •  
  • 3. G. D. Winter, Nature, 193, 293 (1962).
  •  
  • 4. C. D. Hinman, H. I. Maibach, and G. D. Winter, Nature, 200, 377 (1963).
  •  
  • 5. Y. J. Kim, H. G. Park, Y. L. Yang, Y. Yoon, S. Kim, and E. Oh, Biol. Pharm. Bull., 28, 394 (2005).
  •  
  • 6. T. Boontheekul, H. J. Kong, and D. J. Mooney, Biomaterials, 26, 2455 (2005).
  •  
  • 7. J. J. Disa, K. Alizadeh, J. W. Smith, Q. Hu, and P. G. Cordeiro, Ann. Plast. Surg., 46, 405 (2001).
  •  
  • 8. R. B. Davey, A. L. Sparnon, and R. W. Byard, Burns, 26, 393 (2000).
  •  
  • 9. Y. S. Suzuki, M. Tanihara, Y. Nishimura, K. Suzuki, Y. Yamawaki, H. Kudo, Y. Kakimaru, and Y. Shimizu, J. Biomed. Mater. Res., 48, 522 (1999).
  •  
  • 10. C. Wiegand, T. Heinze, and U. -C. Hilper, Wound Repair Regen., 17, 511 (2009).
  •  
  • 11. P. Martin, Science, 276, 75 (1997).
  •  
  • 12. R. Clark, “Wound Repair: overview and general considerations”, in Molecular and Cellular Biiology of Wound Repair, R. Clark, Editor, Plenum Press, New York, p 1 (1995).
  •  
  • 13. S. J. Leibovich and R. Ross, Am. J. Pathol., 78, 71 (1975).
  •  
  • 14. C. J. March, B. Mosley, A. Larsen, D. P. Cerretti, G. Braedt, V. Price, S. Gillis, C. S. Henney, S. R. Kronheim, K. Grabstein, P. J. Conlon, T. P. Hopp, and D. Cosman, Nature, 315, 641 (1985).
  •  
  • 15. A. V. Delgado, A. T. McManus, and J. P. Chambers, Neuropeptides, 37, 355 (2003).
  •  
  • 16. B. Beutler and A. Cerami, Nature, 320, 584 (1986).
  •  
  • 17. S. J. Leibovich, P. J. Polverini, H. M. Shepard, D. M. Wiseman, V. Shively, and N. Nuseir, Nature, 329, 630 (1987).
  •  
  • 18. C. A. Dinarello, Blood, 87, 2095 (1996).
  •  
  • 19. M. K. Angele, M. W. Knoferl, A. Ayala, J. E. Albina, W. G. Cioffi, K. I. Bland, and I. H. Chaudry, Surgery, 126, 279 (1999).
  •  
  • 20. N. J. Trengove, H. Bielefeldt-Ohmann, and M. C. Stacey, Wound Repair Regen., 8, 13 (2000).
  •  
  • 21. T. Kohno, M. T. Brewer, S. L. Baker, P. E. Schwartz, M. W. King, K. K. Hale, C. H. Squires, R. C. Thompson, and J. L. Vannice, Proc. Natl. Acad. Sci. USA, 87, 8331 (1990).
  •  
  • 22. B. Barrick, E. J. Campbell, and C. A. Owen, Wound Repair Regen., 7, 410 (1999).
  •  
  • 23. N. J. Trengove, M. C. Stacey, S. Macauley, N. Bennett, J. Gibson, F. Burslem, G. Murphy, and G. Schultz, Wound Repair Regen., 7, 442 (1999).
  •  
  • 24. B. A. Mast and G. S. Schultz, Wound Repair Regen., 4, 411 (1996).
  •  
  • 25. Y. M. Elçin, V. Dixit, and G. Gitnick, Artif. Organs, 25, 558 (2001).
  •  
  • 26. P. A. Puolakkainen, D. R. Twardzik, J. E. Ranchalis, S. C. Pankey, M. J. Reed, and W. R. Gombotz, J. Surg. Res., 58, 321 (1995).
  •  
  • Polymer(Korea) 폴리머
  • Frequency : Bimonthly(odd)
    ISSN 0379-153X(Print)
    ISSN 2234-8077(Online)
    Abbr. Polym. Korea
  • 2022 Impact Factor : 0.4
  • Indexed in SCIE

This Article

  • 2018; 42(1): 112-118

    Published online Jan 25, 2018

  • 10.7317/pk.2018.42.1.112
  • Received on Jul 28, 2017
  • Revised on Aug 16, 2017
  • Accepted on Aug 22, 2017

Correspondence to

  • Jin Hyun Choi
  • Department of Bio-fibers and Materials Science, Kyungpook National University, Daegu 41566, Korea

  • E-mail: inhchoi@knu.ac.kr