title: Hybrid titanium/biodegradable polymer implants with an hierarchical pore structure as a means to control selective cell movement.
abstract: In order to improve implant success rate, it is important to enhance their responsiveness to the prevailing conditions following implantation. Uncontrolled movement of inflammatory cells and fibroblasts is one of these in vivo problems and the porosity properties of the implant have a strong effect on these. Here, we describe a hybrid system composed of a macroporous titanium structure filled with a microporous biodegradable polymer. This polymer matrix has a distinct porosity gradient to accommodate different cell types (fibroblasts and epithelial cells). The main clinical application of this system will be the prevention of restenosis due to excessive fibroblast migration and proliferation in the case of tracheal implants.
  
  
  RESULTS
  A microbead-based titanium template was filled with a porous Poly (L-lactic acid) (PLLA) body by freeze-extraction method. A distinct porosity difference was obtained between the inner and outer surfaces of the implant as characterized by image analysis and Mercury porosimetry (9.8±2.2 µm vs. 36.7±11.4 µm, p≤0.05). On top, a thin PLLA film was added to optimize the growth of epithelial cells, which was confirmed by using human respiratory epithelial cells. To check the control of fibroblast movement, PKH26 labeled fibroblasts were seeded onto Titanium and Titanium/PLLA implants. The cell movement was quantified by confocal microscopy: in one week cells moved deeper in Ti samples compared to Ti/PLLA.
  
  
  CONCLUSIONS
  In vitro experiments showed that this new implant is effective for guiding different kind of cells it will contact upon implantation. Overall, this system would enable spatial and temporal control over cell migration by a gradient ranging from macroporosity to nanoporosity within a tracheal implant. Moreover, mechanical properties will be dependent mainly on the titanium frame. This will make it possible to create a polymeric environment which is suitable for cells without the need to meet mechanical requirements with the polymeric structure.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM Unité 977, Strasbourg, France.
authors.forename: Nihal Engin
authors.initials: NE
authors.lastname: Vrana
authors.forename: Agnès
authors.initials: A
authors.lastname: Dupret
authors.forename: Christelle
authors.initials: C
authors.lastname: Coraux
authors.forename: Dominique
authors.initials: D
authors.lastname: Vautier
authors.forename: Christian
authors.initials: C
authors.lastname: Debry
authors.forename: Philippe
authors.initials: P
authors.lastname: Lavalle
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001673:Biodegradation, Environmental / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D023903:Coronary Restenosis / Q000628:therapy; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008422:Materials Testing; D051379:Mice; D049329:Nanostructures / Q000737:chemistry; D011108:Polymers / Q000494:pharmacology*; D016062:Porosity / Q000187:drug effects; D019736:Prostheses and Implants; D013499:Surface Properties; D014025:Titanium / Q000494:pharmacology*
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D014025:Titanium