Skip to main content

Advertisement

Springer Nature Link
Log in

Vessel-Derived Decellularized Extracellular Matrices (VdECM): Novel Bio-Engineered Materials for the Wound Healing

  • Original Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Decellularized extracellular matrix (dECM) is a non-cellular scaffold with various functions in tissue engineering and regenerative medicine. Elastin is related to tissue elasticity and scarless wound healing, abundantly found in lung and blood vessel tissues. We studied the characteristics of blood vessel-derived dECM (VdECM) and its effect in wound healing.

Methods:

VdECM was prepared from porcine blood vessel tissue. Weight percentages of elastin of VdECM and atelocollagen were analyzed. Migratory potential of VdECM was tested by scratch assay. VdECM in hydrogel form was microscopically examined, tested for fibroblast proliferation, and examined for L/D staining. Cytokine array of various growth factors in adipocyte-derived mesenchymal stem cell (ASC) media with VdECM was done. Animal wound model showed the wound healing effect of VdECM hydrogel in comparison to other topical agents.

Results:

VdECM contained 6.7 times more elastin than atelocollagen per unit weight. Microscopic view of 0.35% VdECM hydrogel showed consistent distribution. Compared to 3% atelocollagen, 0.35% VdECM showed superior results in fibroblast migration. Fluorescent microscopic findings of L/D assay had highest percentage of cell survival in 1% VdECM compared to atelocollagen. Growth factor expression was drastically amplified when VdECM was added to ASC media. In the animal study model, epithelialization rate in the VdECM group was higher than that of control, oxytetracycline, and epidermal growth factor ointments.

Conclusion:

VdECM contains a high ratio of elastin to collagen and amplifies expressions of many growth factors. It promotes fibroblast migration, proliferation, and survival, and epithelialization comparable to other topical agents.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Wu XJ, Wang YJ, Wu Q, Li Y, Li L, Tang J, et al. Genipin-crosslinked, immunogen-reduced decellularized porcine liver scaffold for bioengineered hepatic tissue. Tissue Eng Regener Med. 2015;12:417–26.

    Article  Google Scholar 

  2. Hielscher AC, Gerecht S. Engineering approaches for investigating tumor angiogenesis: exploiting the role of the extracellular matrix. Cancer Res. 2012;72:6089–96.

    Article  CAS  Google Scholar 

  3. Järveläinen H, Sainio A, Koulu M, Wight TN, Penttinen R. Extracellular matrix molecules: potential targets in pharmacotherapy. Pharmacol Rev. 2009;61:198–223.

    Article  Google Scholar 

  4. Daley WP, Peters SB, Larsen M. Extracellular matrix dynamics in development and regenerative medicine. J Cell Sci. 2008;121:255–64.

    Article  CAS  Google Scholar 

  5. Choi SH, Chun SY, Chae SY, Kim JR, Oh SH, Chung SK, et al. Development of a porcine renal extracellular matrix scaffold as a platform for kidney regeneration. J Biomed Mater Res A. 2015;103:1391–403.

    Article  Google Scholar 

  6. Hashim SNM, Yusof MFH, Zahari W, Noordin K, Kannan TP, Hamid SSA, et al. Angiogenic potential of extracellular matrix of human amniotic membrane. Tissue Eng Regen Med. 2016;13:211–7.

    Article  CAS  Google Scholar 

  7. Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci. 2010;123:4195–200.

    Article  CAS  Google Scholar 

  8. Theocharis AD, Skandalis SS, Tzanakakis GN, Karamanos NK. Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting. Febs J. 2010;277:3904–23.

    Article  CAS  Google Scholar 

  9. Almine JF, Wise SG, Weiss AS. Elastin signaling in wound repair. Birth Defects Res C Embryo Today. 2012;96:248–57.

    Article  CAS  Google Scholar 

  10. Broughton G 2nd, Janis JE, Attinger CE. Wound healing: an overview. Plast Reconstr Surg. 2006;117:1–32.

    Article  Google Scholar 

  11. Daamen WF, Veerkamp JH, van Hest JC, van Kuppevelt TH. Elastin as a biomaterial for tissue engineering. Biomaterials. 2007;28:4378–98.

    Article  CAS  Google Scholar 

  12. Antonicelli F, Bellon G, Debelle L, Hornebeck W. Elastin-elastases and inflamm-aging. Curr Top Dev Biol. 2007;79:99–155.

    Article  CAS  Google Scholar 

  13. Pasquali-Ronchetti I, Baccarani-Contri M. Elastic fiber during development and aging. Microsc Res Tech. 1997;38:428–35.

    Article  CAS  Google Scholar 

  14. de Vries HJ, Middelkoop E, van Heemstra-Hoen M, Wildevuur CH, Westerhof W. Stromal cells from subcutaneous adipose tissue seeded in a native collagen/elastin dermal substitute reduce wound contraction in full thickness skin defects. Lab Invest. 1995;73:532–40.

    Google Scholar 

  15. Kim YS, Majid M, Melchiorri AJ, Mikos AG. Applications of decellularized extracellular matrix in bone and cartilage tissue engineering. Bioeng Transl Med. 2019;4:83–95.

    Article  Google Scholar 

  16. Hafemann B, Ensslen S, Erdmann C, Niedballa R, Zühlke A, Ghofrani K, et al. Use of a collagen/elastin-membrane for the tissue engineering of dermis. Burns. 1999;25:373–84.

    Article  CAS  Google Scholar 

  17. Lamme EN, van Leeuwen RT, Jonker A, van Marle J, Middelkoop E. Living skin substitutes: survival and function of fibroblasts seeded in a dermal substitute in experimental wounds. J Invest Dermatol. 1998;111:989–95.

    Article  CAS  Google Scholar 

  18. Almine JF, Bax DV, Mithieux SM, Nivison-Smith L, Rnjak J, Waterhouse A, et al. Elastin-based materials. Chem Soc Rev. 2010;39:3371–9.

    Article  CAS  Google Scholar 

  19. Dzobo K, Motaung K, Adesida A. Recent trends in decellularized extracellular matrix bioinks for 3D printing: an updated review. Int J Mol Sci. 2019;20:18.

    Article  Google Scholar 

  20. Xia Z, Guo X, Yu N, Zeng A, Si L, Long F, et al. The application of decellularized adipose tissue promotes wound healing. Tissue Eng Regen Med. 2020;17:863–74.

    Article  CAS  Google Scholar 

  21. Shiratsuchi E, Nakaba M, Yamada M. Elastin hydrolysate derived from fish enhances proliferation of human skin fibroblasts and elastin synthesis in human skin fibroblasts and improves the skin conditions. J Sci Food Agric. 2016;96:1672–7.

    Article  CAS  Google Scholar 

  22. de Castro Brás LE, Frangogiannis NG. Extracellular matrix-derived peptides in tissue remodeling and fibrosis. Matrix Biol. 2020;91–92:176–87.

    Article  Google Scholar 

  23. Almine JF, Wise SG, Hiob M, Singh NK, Tiwari KK, Vali S, et al. Elastin sequences trigger transient proinflammatory responses by human dermal fibroblasts. FASEB J. 2013;27:3455–65.

    Article  CAS  Google Scholar 

  24. Senior RM, Griffin GL, Mecham RP, Wrenn DS, Prasad KU, Urry DW. Val-Gly-Val-Ala-Pro-Gly, a repeating peptide in elastin, is chemotactic for fibroblasts and monocytes. J Cell Biol. 1984;99:870–4.

    Article  CAS  Google Scholar 

  25. Bisaccia F, Morelli MA, De Biasi M, Traniello S, Spisani S, Tamburro AM. Migration of monocytes in the presence of elastolytic fragments of elastin and in synthetic derivates. Structure-activity relationships. Int J Pept Protein Res. 1994;44:332–41.

  26. Wachi H, Seyama Y, Yamashita S, Suganami H, Uemura Y, Okamoto K, et al. Stimulation of cell proliferation and autoregulation of elastin expression by elastin peptide VPGVG in cultured chick vascular smooth muscle cells. FEBS Lett. 1995;368:215–9.

    Article  CAS  Google Scholar 

  27. Rnjak-Kovacina J, Wise SG, Li Z, Maitz PK, Young CJ, Wang Y, et al. Electrospun synthetic human elastin:collagen composite scaffolds for dermal tissue engineering. Acta Biomater. 2012;8:3714–22.

    Article  CAS  Google Scholar 

  28. Machula H, Ensley B, Kellar R. Electrospun tropoelastin for delivery of therapeutic adipose-derived stem cells to full-thickness dermal wounds. Adv Wound Care (New Rochelle). 2014;3:367–75.

    Article  Google Scholar 

  29. Nivison-Smith L, Rnjak J, Weiss AS. Synthetic human elastin microfibers: stable cross-linked tropoelastin and cell interactive constructs for tissue engineering applications. Acta Biomater. 2010;6:354–9.

    Article  CAS  Google Scholar 

  30. Lynn AK, Yannas IV, Bonfield W. Antigenicity and immunogenicity of collagen. J Biomed Mater Res B Appl Biomater. 2004;71:343–54.

    Article  CAS  Google Scholar 

  31. Ochiya T, Takahama Y, Nagahara S, Sumita Y, Hisada A, Itoh H, et al. New delivery system for plasmid DNA in vivo using atelocollagen as a carrier material: the minipellet. Nat Med. 1999;5:707–10.

    Article  CAS  Google Scholar 

  32. Pastar I, Stojadinovic O, Yin NC, Ramirez H, Nusbaum AG, Sawaya A, et al. Epithelialization in wound healing: a comprehensive review. Adv Wound Care (New Rochelle). 2014;3:445–64.

    Article  Google Scholar 

  33. Rousselle P, Montmasson M, Garnier C. Extracellular matrix contribution to skin wound re-epithelialization. Matrix Biol. 2019;75:12–26.

    Article  Google Scholar 

Download references

Acknowledgement

This work was financially supported by the Ministry of Trade Industry and Energy of Korea (20000325).

Author information

Authors and Affiliations

  1. Department of Plastic and Reconstructive Surgery, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Republic of Korea

    Chae Rim Lee & Suk-Ho Moon

  2. Department of Plastic and Reconstructive Surgery, Yeouido St. Mary′s Hospital, The Catholic University of Korea, 10, 63Ro, Yeongdeungpo-Gu, Seoul, 07345, Republic of Korea

    Yoon Jae Lee

  3. Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seocho-Gu, Seoul, 06591, Republic of Korea

    Bo Young Kwon, Su Jin Lee, Yeon Hee Ryu & Jong-Won Rhie

Authors
  1. Chae Rim Lee
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Yoon Jae Lee
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Bo Young Kwon
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Su Jin Lee
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Yeon Hee Ryu
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Jong-Won Rhie
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Suk-Ho Moon
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

Data collection: YHR, SJL, BYK. Analysis and Interpretation of results: CRL, YHR, SJL, BYK, SHM, JWR. Draft Manuscript preparation: CRL, SJL, SHM.

Corresponding author

Correspondence to Suk-Ho Moon.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Statement

The animal studies were performed after receiving approval of the Institutional Animal Care and Use Committee (IACUC) in Catholic University of Korea, College of Medicine (IACUC approval No. CUMC-2021-0267-03)

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, C.R., Lee, Y.J., Kwon, B.Y. et al. Vessel-Derived Decellularized Extracellular Matrices (VdECM): Novel Bio-Engineered Materials for the Wound Healing. Tissue Eng Regen Med 20, 59–67 (2023). https://doi.org/10.1007/s13770-022-00511-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-022-00511-y

Keywords