title: Modification of macroporous titanium tracheal implants with biodegradable structures: tracking in vivo integration for determination of optimal in situ epithelialization conditions.
abstract: Previously, we showed that macroporous titanium implants, colonized in vivo together with an epithelial graft, are viable options for tracheal replacement in sheep. To decrease the number of operating steps, biomaterial-based replacements for epithelial graft and intramuscular implantation were developed in the present study. Hybrid microporous PLLA/titanium tracheal implants were designed to decrease initial stenosis and provide a surface for epithelialization. They have been implanted in New Zealand white rabbits as tracheal substitutes and compared to intramuscular implantation samples. Moreover, a basement membrane like coating of the implant surface was also designed by Layer-by-Layer (LbL) method with collagen and alginate. The results showed that the commencement of stenosis can be prevented by the microporous PLLA. For determination of the optimum time point of epithelialization after implantation, HPLC analysis of blood samples, C-reactive protein (CRP), and Chromogranin A (CGA) analyses and histology were carried out. Following 3 weeks the implant would be ready for epithelialization with respect to the amount of tissue integration. Calcein-AM labeled epithelial cell seeding showed that after 3 weeks implant surfaces were suitable for their attachment. CRP readings were steady after an initial rise in the first week. Cross-linked collagen/alginate structures show nanofibrillarity and they form uniform films over the implant surfaces without damaging the microporosity of the PLLA body. Human respiratory epithelial cells proliferated and migrated on these surfaces which provided a better alternative to PLLA film surface. In conclusion, collagen/alginate LbL coated hybrid PLLA/titanium implants are viable options for tracheal replacement, together with in situ epithelialization.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, 11 Rue Humann, 67085 Strasbourg, France.
authors.forename: Nihal Engin
authors.initials: NE
authors.lastname: Vrana
authors.forename: Agnes
authors.initials: A
authors.lastname: Dupret-Bories
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bach
authors.forename: Christophe
authors.initials: C
authors.lastname: Chaubaroux
authors.forename: Christelle
authors.initials: C
authors.lastname: Coraux
authors.forename: Dominique
authors.initials: D
authors.lastname: Vautier
authors.forename: Fouzia
authors.initials: F
authors.lastname: Boulmedais
authors.forename: Youssef
authors.initials: Y
authors.lastname: Haikel
authors.forename: Christian
authors.initials: C
authors.lastname: Debry
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Metz-Boutigue
authors.forename: Philippe
authors.initials: P
authors.lastname: Lavalle
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D002460:Cell Line; D020099:Coated Materials, Biocompatible; D003251:Constriction, Pathologic / Q000601:surgery*; D006651:Histocytochemistry; D006801:Humans; D011817:Rabbits; D020545:Respiratory Mucosa / Q000166:cytology / Q000502:physiology; D013499:Surface Properties; D014025:Titanium / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000601:surgery*
chemical_list: D020099:Coated Materials, Biocompatible; D014025:Titanium