Enhanced extracellular matrix synthesis using collagen dressings loaded with Artemisia absinthium plant extract

Abstract

The aim of this study was to develop three-dimensional porous composites of collagen (Col) incorporating polyphenolic-rich wormwood extract and to investigate their interaction with human skin cells, in order to optimize wound healing treatments. The scaffolds’ ultrastructure was observed by scanning electron microscopy, and biodegradability and bioactive compounds release were investigated in physiologic environment. Interaction of composites in direct and indirect contact with human skin cells was evaluated using two in vitro experimental models. ColWE scaffolds presented high porosity, swelling degree, and increased stability against enzymatic degradation, compared to Col scaffold. Composite scaffolds incorporating higher quantities of wormwood extract allowed better control of polyphenolics release. ColWE 0.5 variant favored the attachment and proliferation of human dermal fibroblasts and keratinocyte cells. In addition, the composite scaffold stimulated the synthesis of skin extracellular matrix components. All these results demonstrated that ColWE composites with improved physico-chemical and biological properties could be used in advanced wound healing applications.

Keywords

Composite material cytotoxicity extracellular matrix polyphenols skin cells wormwood

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References

Barrientos

Stojadinovic

Golinko

et al . Growth factors and cytokines in wound healing. Wound Repair Regen 2008; 16(5): 585–601.

Mogosanu

Grumezescu

AM.

Natural and synthetic polymers for wounds and burns dressing. Int J Pharm 2014; 463(2): 127–136.

Boateng

Matthews

Stevens

et al . Wound healing dressings and drug delivery systems: a review. J Pharm Sci 2008; 97(8): 2892–2923.

Moura

Dias

Carvalho

et al . Recent advances on the development of wound dressings for diabetic foot ulcer treatment—a review. Acta Biomater 2013; 9(7): 7093–7114.

Malafaya

Silva

Reis

RL.

Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Adv Drug Deliv Rev 2007; 59(4–5): 207–233.

Dong

Application of collagen scaffold in tissue engineering: recent advances and new perspectives. Polymers 2016; 8(2): 42–62.

Uemura

Yamaguchi

et al . Effect of enzymatically cross-linked tilapia scale collagen for osteoblastic differentiation of human mesenchymal stem cells. J Bioact Compat Pol 2016; 31(1): 31–41.

Chattopadhyay

Raines

RT.

Biomaterials for wound healing. Biopolymers 2014; 101(8): 821–833.

Piraino

Selimovic

A current view of functional biomaterials for wound care, molecular and cellular therapies. Biomed Res Int 2015; 2015: 403801.

10.

Budovsky

Yarmolinsky

Ben-Shabat

Effect of medicinal plants on wound healing. Wound Repair Regen 2015; 23(2): 171–183.

11.

Bora

Sharma

The genus Artemisia: a comprehensive review. Pharm Biol 2011; 49(3): 101–109.

12.

Canadanovic-Brunet

Djilas

Cetkovic

et al . Free-radical scavenging activity of wormwood (Artemisia absinthium L) extracts. J Sci Food Agric 2005; 85: 265–272.

13.

Bora

Sharma

Evaluation of antioxidant and free-radical scavenging potential of

Artemisia absinthium. Pharm Biol 2011; 49(1): 1216–1223.

14.

Erel

Reznicek

Senol

et al . Antimicrobial and antioxidant properties of Artemisia L. species from western Anatolia. Turk J Biol 2012; 36: 75–84.

15.

Naseri-Nosar

Farzamfar

Salehi

et al . Erythropoietin/Aloe Vera-releasing wet-electrospun polyvinyl alcohol/chitosan sponge-like wound dressing: in vitro and in vivo studies. J Bioact Compat Pol 2017; 33: 269–281.

16.

Andreu

Mendoza

Arruebo

et al . Smart dressings based on nanostructured fibers containing natural origin antimicrobial, anti-inflammatory, and regenerative compounds. Materials 2015; 8(8): 5154–5193.

17.

Das

Behera

Singh

et al . Progress in the development and applicability of potential medicinal plant extract-conjugated polymeric constructs for wound healing and tissue regeneration. Phytother Res 2016; 30(12): 1895–1904.

18.

Gaspar

Craciunescu

Moldovan

et al . New composites collagen-polyphenols as potential dressing for wound care. Rom J Biochem 2012; 49(2): 173–181.

19.

Francesko

Rocasalbas

Tourino

et al . Cross-linked collagen sponges loaded with plant polyphenols with inhibitory activity towards chronic wound enzymes. Biotechnol J 2011; 6(10): 1208–1218.

20.

Kumar

Kirubanandan

Sripriya

et al . Triphala incorporated collagen sponge—a smart biomaterial for infected dermal wound healing. J Surg Res 2010; 158(1): 162–170.

21.

Yao

Gao

et al . Improving the angiogenic potential of collagen matrices by covalent incorporation of Astragalus polysaccharides. Int J Burns Trauma 2011; 1(1): 17–26.

22.

Jithendra

Rajam

Kalaivani

et al . Preparation and characterization of Aloe Vera blended collagen-chitosan composite scaffold for tissue engineering applications. ACS Appl Mater Interfaces 2013; 5(15): 7291–7298.

23.

Craciunescu

Constantin

Gaspar

et al . Evaluation of antioxidant and cytoprotective activities of Arnica montana L. and Artemisia absinthium L. ethanolic extracts. Chem Cent J 2012; 6(1): 97–108.

24.

Craciunescu

Moldovan

. Designing bio-inspired composite materials for medical applications. In: Cuppoletti

(ed.) Nanocomposites and polymers with analytical methods. 1st ed. Rijeka: InTech, 2011, pp. 309–334.

25.

Zhang

Cui

Liao

et al . Synthesis and biocompatibility of porous nano-hydroxyapatite/collagen/alginate composite. J Mater Sci Mater Med 2003; 14(7): 641–645.

26.

Atala

Lanza

RP.

Methods of tissue engineering. Orlando, FL: Academic Press, 2002.

27.

Singleton

Orthofer

Lamuela-Raventos

RM.

Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. In: Abelson

Simon

(eds) Methods in enzymology. San Diego, CA: Academic Press, 1999, pp. 152–177.

28.

Villegas

McPhaul

Establishment and culture of human skin fibroblasts. Curr Protoc Mol Biol 2005; 71: 283.

29.

Bradford

MM.

A rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–254.

30.

Moldovan

Gaspar

Toma

et al . Comparison of polyphenolic content and antioxidant capacity of five Romanian traditional medicinal plants. Rev Chim 2011; 62(3): 299–303.

31.

Stanciuc

Gaspar

Moldovan

et al . In vitro antimicrobial activity of Romanian medicinal plants hydroalcoholic extracts on planktonic and adhered cells. Roum Arch Microbiol Immunol 2011; 70(1): 11–14.

32.

Rodriguez-Vazquez

Vega-Ruiz

Ramos-Zuniga

et al . Chitosan and its potential use as a scaffold for tissue engineering in regenerative medicine. Biomed Res Int 2015; 2015: 821279.

33.

Murphy

Haugh

O’Brien

The effect of mean pore size on cell attachment, proliferation and migration in collagen-glycosaminoglycan scaffolds for bone tissue engineering. Biomaterials 2010; 31(3): 461–466.

34.

Simon

CG.

Self-hardening calcium phosphate cement-mesh composite: reinforcement, macropores and cell response. J Biomed Mat Res 2004; 69(2): 267–278.

35.

Loh

Choong

Three-dimensional scaffolds for tissue engineering applications: role of porosity and pore size. Tissue Eng Part B Rev 2013; 19(6): 485–502.

36.

Macchetta

Turner

Bowen

CR.

Fabrication of HA/TCP scaffolds with a graded and porous structure using a camphene-based freeze-casting method. Acta Biomater 2009; 5(4): 1319–1327.

37.

Jarquin-Yanez

Arenas-Alatorre

Pinon-Zarate

et al . Structural effect of different EDC crosslinker concentration in gelatin-hyaluronic acid scaffolds. J Bioeng Biomed Sci 2016; 6: 182.

38.

Krishnamoorthy

Madhan

Sadulla

et al . Stabilization of collagen by the plant polyphenolics Acacia mollissima and Terminalia chebula. J Appl Polym Sci 2008; 108: 199–205.

39.

Albu

Titorencu

Ghica

. Collagen-based drug delivery systems for tissue engineering. In: Pignatello

(ed.) Biomaterials applications for nanomedicine. 1st ed. Rijeka: InTech, 2011, pp. 333–358.

40.

Cheirmadurai

Thanikaivelan

Murali

Highly biocompatible collagen-Delonix regia seed polysaccharide hybrid scaffolds for antimicrobial wound dressing. Carbohydr Polym 2016; 137: 584–593.

41.

Madhan

Subramanian

Rao

et al . Stabilization of collagen using plant polyphenol: role of catechin. Int J Biol Macromol 2005; 37(1–2): 47–53.

42.

Raju

Prakash

Rao

et al . Effect of tablet surface area and surface area/volume on drug release from lamivudine extended release matrix tablets. Int J Pharm Sci Nanotechnol 2010; 3(1): 872–876.

43.

Zhang

Wang

Cheng

et al . Apigenin induces dermal collagen synthesis via smad2/3 signaling pathway. Eur J Histochem 2015; 59(2): 98–106.

44.

Moldovan

Buzgariu

Craciunescu

et al . Preparation of porous collagen matrices and their interaction with different cell types. In: Gruev

Nikolova

Donev

(eds) Proceedings of the Balkan scientific conference of biology. (1st ed). Plovdiv: Plovdiv University Press, 2005, pp. 671–681.

45.

Zheng

GQ.

Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med 1994; 60(1): 54–57.

46.

Ivanescu

Vlase

Corciova

et al . HPLC-DAD-MS study of polyphenols from Artemisia absinthium, A. annua, and A. vulgaris. Chem Nat Comp 2010; 46(3): 468–470.

47.

Nazaruk

Galicka

The influence of selected flavonoids from the leaves of Cirsium palustre (L.) Scop. on collagen expression in human skin fibroblasts. Phytother Res 2014; 28(9): 1399–1405.