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Neue Möglichkeiten der Augenoberflächenrekonstruktion

Membranen aus Kollagen und biokompatiblen Elastomernanofasern

New possibilities for ocular surface reconstruction

Collagen membranes and biocompatible elastomer nanofibers

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Zusammenfassung

Hintergrund

Im Zuge der technischen Verbesserungen im Bereich des Tissue Engineering erarbeiten diverse Arbeitsgruppen Alternativen zu konventionellen Methoden der Oberflächenrekonstruktion der Hornhaut. Dieses Bestreben entspringt der Not, dass die Amnionmembran als etablierte Biomatrix für die Oberflächenrekonstruktion wenig standardisiert hergestellt wird, hohen strukturellen Variationen unterliegt und nicht überall verfügbar ist.

Fragestellung

Es erfolgt eine Darlegung neuer Ansätze zur Rekonstruktion der Augenoberfläche mittels Membranen aus Kollagenen und aus bioverträglichen Polymeren.

Material und Methoden

Basierend auf einer Literaturrecherche wird ein Überblick über wesentliche Untersuchungsergebnisse zu kollagenen Biomatrizes an der Hornhautoberfläche gegeben. Zusätzlich werden eigene Erfahrungen mit neuartigen Biomatrizes für die Anwendung im Bereich der Hornhaut dargestellt.

Ergebnisse

Laborexperimentelle Arbeiten bestätigen den vorgestellten Materialien eine hohe Bioverträglichkeit und lassen ihre direkte Anwendung an der Hornhautoberfläche bei nicht heilenden Oberflächendefekten oder aber ihre Verwendung als Träger epithelialer Stammzellen für die Transplantation auf die Hornhaut auch am Menschen als vielversprechend erscheinen. Klinische Anwendungen biosynthetischer Biomatrizes im Bereich der Hornhaut sind jedoch im Klinikalltag bislang nicht etabliert, und auch klinische Studien gibt es nur vereinzelt.

Schlussfolgerung

Obgleich sich ein Großteil der vorgestellten Materialien im Wesentlichen in laborexperimentellen Stadien befindet, ist eine Translation in die Klinik denkbar und von hohem therapeutischem Interesse.

Abstract

Background

Amniotic membranes have been used for many years for reconstruction of the ocular surface. Despite having anti-inflammatory and antiangiogenic properties as well as being suitable as a carrier for corneal epithelial cells, amniotic membranes also have some limitations for use at the human cornea: availability is limited, there are major interindividual variations in structure and growth factor content and are not free from the risk of disease transmission. Progress in tissue engineering has been made aiming at the development and improvement of alternative biomaterials.

Objectives

This article presents new approaches for reconstruction of the corneal surface with collagen-based biomaterials and polymers.

Material and methods

Electronic databases were searched for articles which evaluated collagenous biomaterials for use at the corneal surface. In addition the authors’ own experiences with novel biomaterials are described.

Results

In vitro evaluation of the described biomaterials suggested a high biocompatibility with corneal epithelial cells in cell cultures. In vivo experiments with these materials in animal corneas demonstrated a certain variability in degradation and remodeling. Although some materials showed promising experimental results none of these are established in the clinical routine and only few clinical studies have so far been conducted with collagen-based biomaterials.

Conclusion

Although the majority of the described biomaterials are currently still in the experimental stage, a transfer into the clinical routine is conceivable and of great therapeutic interest.

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Literatur

  1. Meller D, Pauklin M, Thomasen H et al (2011) Amniotic membrane transplantation in the human eye. Dtsch Arztebl Int 108:243–248

    PubMed Central  PubMed  Google Scholar 

  2. Hopkinson A, McIntosh RS, Tighe PJ et al (2006) Amniotic membrane for ocular surface reconstruction: donor variations and the effect of handling on TGF-beta content. Invest Ophthalmol Vis Sci 47:4316–4322

    Article  PubMed  Google Scholar 

  3. Gicquel JJ, Dua HS, Brodie A et al (2009) Epidermal growth factor variations in amniotic membrane used for ex vivo tissue constructs. Tissue Eng Part A 15:1919–1927

    Article  CAS  PubMed  Google Scholar 

  4. Connon CJ, Doutch J, Chen B et al (2010) The variation in transparency of amniotic membrane used in ocular surface regeneration. Br J Ophthalmol 94:1057–1061

    Article  CAS  PubMed  Google Scholar 

  5. Wong SC, Baji A, Leng S (2008) Effect of fiber diameter on tensile properties of electrospun poly(ɛ-caprolactone). Polymer 49:4713–4722

    Article  CAS  Google Scholar 

  6. Baker BM, Handorf AM, Ionescu LC et al (2009) New directions in nanofibrous scaffolds for soft tissue engineering and regeneration. Expert Rev Med Devices 6:515–532

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Kenar H, Kose GT, Toner M et al (2011) A 3D aligned microfibrous myocardial tissue construct cultured under transient perfusion. Biomaterials 32:5320–5329

    Article  CAS  PubMed  Google Scholar 

  8. Ruberti JW, Zieske JD (2008) Prelude to corneal tissue engineering – gaining control of collagen organization. Prog Retin Eye Res 27:549–577

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Ihanamaki T, Pelliniemi LJ, Vuorio E (2004) Collagens and collagen-related matrix components in the human and mouse eye. Prog Retin Eye Res 23:403–434

    Article  CAS  PubMed  Google Scholar 

  10. Qazi Y, Wong G, Monson B et al (2010) Corneal transparency: genesis, maintenance and dysfunction. Brain Res Bull 81:198–210

    Article  PubMed Central  PubMed  Google Scholar 

  11. Builles N, Janin-Manificat H, Malbouyres M et al (2010) Use of magnetically oriented orthogonal collagen scaffolds for hemi-corneal reconstruction and regeneration. Biomaterials 31:8313–8322

    Article  CAS  PubMed  Google Scholar 

  12. Crabb RA, Chau EP, Evans MC et al (2006) Biomechanical and microstructural characteristics of a collagen film-based corneal stroma equivalent. Tissue Eng 12:1565–1575

    Article  PubMed  Google Scholar 

  13. Deshpande P, Ramachandran C, Sefat F et al (2013) Simplifying corneal surface regeneration using a biodegradable synthetic membrane and limbal tissue explants. Biomaterials 34:5088–5106

    Article  CAS  PubMed  Google Scholar 

  14. Liu Y, Gan L, Carlsson DJ et al (2006) A simple, cross-linked collagen tissue substitute for corneal implantation. Invest Ophthalmol Vis Sci 47:1869–1875

    Article  PubMed  Google Scholar 

  15. Orwin EJ, Borene ML, Hubel A (2003) Biomechanical and optical characteristics of a corneal stromal equivalent. J Biomech Eng 125:439–444

    Article  PubMed  Google Scholar 

  16. Wu J, Du Y, Watkins SC et al (2012) The engineering of organized human corneal tissue through the spatial guidance of corneal stromal stem cells. Biomaterials 33:1343–1352

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Rafat M, Li F, Fagerholm P et al (2008) PEG-stabilized carbodiimide crosslinked collagen-chitosan hydrogels for corneal tissue engineering. Biomaterials 29:3960–3972

    Article  CAS  PubMed  Google Scholar 

  18. Hu X, Lui W, Cui L et al (2005) Tissue engineering of nearly transparent corneal stroma. Tissue Eng 11:1710–1717

    Article  CAS  PubMed  Google Scholar 

  19. Lawrence BD, Marchant JK, Pindrus MA et al (2009) Silk film biomaterials for cornea tissue engineering. Biomaterials 30:1299–1308

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Schmitt FO, Levine L, Drake MP et al (1964) The antigenicity of tropocollagen. Proc Natl Acad Sci U S A 51:493–497

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Staatz WD, Fok KF, Zutter MM et al (1991) Identification of a tetrapeptide recognition sequence for the alpha 2 beta 1 integrin in collagen. J Biol Chem 266:7363–7367

    CAS  PubMed  Google Scholar 

  22. Gullberg D, Terracio L, Borg TK et al (1989) Identification of integrin-like matrix receptors with affinity for interstitial collagens. J Biol Chem 264:12686–12694

    CAS  PubMed  Google Scholar 

  23. Gullberg D, Turner DC, Borg TK et al (1990) Different beta 1-integrin collagen receptors on rat hepatocytes and cardiac fibroblasts. Exp Cell Res 190:254–264

    Article  CAS  PubMed  Google Scholar 

  24. Geggel HS, Friend J, Thoft RA (1985) Collagen gel for ocular surface. Invest Ophthalmol Vis Sci 26:901–905

    CAS  PubMed  Google Scholar 

  25. Dunn MW, Nishihara T, Stenzel KH et al (1967) Collagen-derived membrane: corneal implantation. Science 157:1329–1330

    Article  CAS  PubMed  Google Scholar 

  26. Payrau P, Offret G, Faure JP et al (1963) Experimental trial of the use of collagen in ophthalmology. Arch Ophtalmol Rev Gen Ophtalmol 23:129–142

    Google Scholar 

  27. Duan X, McLaughlin C, Griffith M et al (2007) Biofunctionalization of collagen for improved biological response: scaffolds for corneal tissue engineering. Biomaterials 28:78–88

    Article  CAS  PubMed  Google Scholar 

  28. Fagerholm P, Lagali NS, Carlsson DJ et al (2009) Corneal regeneration following implantation of a biomimetic tissue-engineered substitute. Clin Transl Sci 2:162–164

    Article  CAS  PubMed  Google Scholar 

  29. Simsek NA, Ay GM, Tugal-Tutkun I et al (1996) An experimental study on the effect of collagen shields and therapeutic contact lenses on corneal wound healing. Cornea 15:612–616

    CAS  PubMed  Google Scholar 

  30. Groden LR, White W (1990) Porcine collagen corneal shield treatment of persistent epithelial defects following penetrating keratoplasty. CLAO J 16:95–97

    CAS  PubMed  Google Scholar 

  31. Phinney RB, Schwartz SD, Lee DA et al (1988) Collagen-shield delivery of gentamicin and vancomycin. Arch Ophthalmol 106:1599–1604

    Article  CAS  PubMed  Google Scholar 

  32. Sawusch MR, O’Brien TP, Updegraff SA (1989) Collagen corneal shields enhance penetration of topical prednisolone acetate. J Cataract Refract Surg 15:625–628

    Article  CAS  PubMed  Google Scholar 

  33. Fagerholm P, Lagali NS, Merrett K et al (2010) A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a phase 1 clinical study. Sci Transl Med 2 (46):46–61

    Article  Google Scholar 

  34. Hackett JM, Lagali N, Merrett K et al (2011) Biosynthetic corneal implants for replacement of pathologic corneal tissue: performance in a controlled rabbit alkali burn model. Invest Ophthalmol Vis Sci 52:651–657

    Article  CAS  PubMed  Google Scholar 

  35. Liu W, Deng C, McLaughlin CR et al (2009) Collagen-phosphorylcholine interpenetrating network hydrogels as corneal substitutes. Biomaterials 30:1551–1559

    Article  CAS  PubMed  Google Scholar 

  36. McLaughlin CR, Acosta MC, Luna C et al (2010) Regeneration of functional nerves within full thickness collagen-phosphorylcholine corneal substitute implants in guinea pigs. Biomaterials 31:2770–2778

    Article  CAS  PubMed  Google Scholar 

  37. Lagali NS, Griffith M, Shinozaki N et al (2007) Innervation of tissue-engineered corneal implants in a porcine model: a 1-year in vivo confocal microscopy study. Invest Ophthalmol Vis Sci 48:3537–3544

    Article  PubMed  Google Scholar 

  38. Petsch C, Schlotzer-Schrehardt U, Meyer-Blazejewska E et al (2014) Novel collagen membranes for the reconstruction of the corneal surface. Tissue Eng Part A 20(17–18):2378–2389

  39. Petsch C, Schlötzer-Schrehardt U, Frey M et al (2013) Optimized culturing conditions for limbal epithelial cells cultivated on semi-synthetic collagen matrices. Invest Ophthalmol Vis Sci 54:E-Abstract 548

    Google Scholar 

  40. Torbet J, Malbouyres M, Builles N et al (2007) Orthogonal scaffold of magnetically aligned collagen lamellae for corneal stroma reconstruction. Biomaterials 28:4268–4276

    Article  CAS  PubMed  Google Scholar 

  41. Deng C, Li F, Hackett JM et al (2010) Collagen and glycopolymer based hydrogel for potential corneal application. Acta Biomater 6:187–194

    Article  CAS  PubMed  Google Scholar 

  42. Mi S, Chen B, Wright B et al (2010) Plastic compression of a collagen gel forms a much improved scaffold for ocular surface tissue engineering over conventional collagen gels. J Biomed Mater Res A 95:447–453

    Article  PubMed  Google Scholar 

  43. Levis HJ, Brown RA, Daniels JT (2010) Plastic compressed collagen as a biomimetic substrate for human limbal epithelial cell culture. Biomaterials 31:7726–7737

    Article  CAS  PubMed  Google Scholar 

  44. Fagerholm P, Lagali NS, Ong JA et al (2014) Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold. Biomaterials 35:2420–2427

    Article  CAS  PubMed  Google Scholar 

  45. Gao J, Crapo P, Nerem R et al (2008) Co-expression of elastin and collagen leads to highly compliant engineered blood vessels. J Biomed Mater Res A 85:1120–1128

    Article  PubMed  Google Scholar 

  46. Redenti S, Neeley WL, Rompani S et al (2009) Engineering retinal progenitor cell and scrollable poly(glycerol-sebacate) composites for expansion and subretinal transplantation. BioMaterials 30:3405–3414

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Sundback CA, Shyu JY, Wang Y et al (2005) Biocompatibility analysis of poly(glycerol sebacate) as a nerve guide material. Biomaterials 26:5454–5464

    Article  CAS  PubMed  Google Scholar 

  48. Wang Y, Ameer GA, Sheppard BJ et al (2002) A tough biodegradable elastomer. Nat Biotechnol 20:602–606

    Article  CAS  PubMed  Google Scholar 

  49. Lee EJ, Vunjak-Novakovic G, Wang Y et al (2009) A biocompatible endothelial cell delivery system for in vitro tissue engineering. Cell Transplant 18:731–743

    Article  PubMed Central  PubMed  Google Scholar 

  50. Salehi S, Bahners T, Gutmann JS et al (2014) Characterization of structural, mechanical and nano-mechanical properties of electrospun PGS/PCL fibers. RSC Adv 4:16951–16957

    Article  CAS  Google Scholar 

  51. Salehi S, Fathi M, Javanmard SH et al (2014) Generation of PGS/PCL-blend nanofibrous scaffolds mimicking corneal stroma structure. Macromol Mat Eng 299:455–469

    Article  CAS  Google Scholar 

  52. Byfield FJ, Reen RK, Shentu TP et al (2009) Endothelial actin and cell stiffness is modulated by substrate stiffness in 2D and 3D. J Biomech 42:1114–1119

    Article  PubMed Central  PubMed  Google Scholar 

  53. Stevens MM, George JH (2005) Exploring and engineering the cell surface interface. Science 310:1135–1138

    Article  CAS  PubMed  Google Scholar 

  54. Kenawy ER, Layman JM, Watkins JR et al (2003) Electrospinning of poly(ethylene-co-vinyl alcohol) fibers. Biomaterials 24:907–913

    Article  CAS  Google Scholar 

  55. Salehi S, Gruenert AK, Bahners T et al (2014) New nanofibrous scaffold for corneal tissue engineering. Klin Monatsbl Augenheilkd 231(6):626–630

    Article  CAS  PubMed  Google Scholar 

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Einhaltung ethischer Richtlinien

Interessenkonflikt. T. Fuchsluger, S. Salehi, C. Petsch und B. Bachmann geben an, dass kein Interessenkonflikt besteht. Alle im vorliegenden Manuskript beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethik-Kommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Von allen beteiligten Patienten liegt eine Einverständniserklärung vor.

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Correspondence to B. Bachmann.

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Fuchsluger, T., Salehi, S., Petsch, C. et al. Neue Möglichkeiten der Augenoberflächenrekonstruktion. Ophthalmologe 111, 1019–1026 (2014). https://doi.org/10.1007/s00347-013-3010-z

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