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.

Orthopedic bioactive implants: Hydrogel enrichment of macroporous titanium for the delivery of mesenchymal stem cells and strontium

“…This macroporous titanium is characterized by multiple layers of hexagonal pores with a 640 lm diameter, 8 macroporosity that facilitates cell migration and bone deposition. 9 It has been shown that porous titanium implants can be enriched, either directly [10][11][12] or by association with biocompatible hydrogels, [13][14][15][16] with antibiotics, 14 VEGF, 15 and FGF-2. 16 To improve implant osseointegration, osteogenic factors can be used for implant enrichment.…”

Review: the potential impact of surface crystalline states of titanium for biomedical applications

“…These unknown factors are supposed to be delivered by some specific surface features of the TiO2 layer, such as crystalline phase, exposed facet, electron structure and surface defect, which together could create a chemically active solid surface that may catalyze some heterogeneous redox reactions or facilitate the adsorption and desorption of macromolecules in the human body. It must be noted that the effect of such surface features have yet been investigated extensively in conjunction with TiO2 photocatalysts and semiconductors but they have been disregarded in relation to indwelling implants 3.2.Surface modification of Titanium to control cell response Cell attachment and spreading on titanium is a well-established phenomenon (Le Guéhennec et al, 2007, Sjöström et al, 2013, Koenig et al, 2016, Schultz et al, 2007, Vrana et al, 2012, Regis et al, 2015. Nevertheless, lack of osseointegration on untreated titanium implants is often associated with implant failure mainly due to the difficulty of the material to establish a strong bond with bone.…”

Multi-Scale Modification of Metallic Implants With Pore Gradients, Polyelectrolytes and Their Indirect Monitoring <em>In vivo</em>

“…However, continuation of this process can lead to restenosis and in the presence of the pore gradient due to the PLLA structure, no fibroblast presence was observed after 6 weeks of implantation 20 . During this period HPLC analysis showed distinct peaks that fluctuate during the time course of implantation.…”

“…Mercury Porosimeter measurements showed distinct peaks that correspond to the pores on the both sides of the implant and the smaller interdispersed pores. However the more crucial data is the difference between the porosities of intraluminal and extraluminal surfaces, which can be analyzed by Image J for pore size distribution with a scanning electron microscope (SEM) 20 . For verification of the pore gradient, freeze-fracture the samples and observe the cross-section with SEM.…”