Cyclodextrin modified PLLA parietal reinforcement implant with prolonged antibacterial activity.

The use of textile meshes in hernia repair is widespread in visceral surgery. Though, mesh infection is a complication that may prolong the patient recovery period and consequently presents an impact on public health economy. Such concern can be avoided thanks to a local and extended antibiotic release on the operative site. In recent developments, poly-l-lactic acid (PLLA) has been used in complement of polyethyleneterephthalate (Dacron®) (PET) or polypropylene (PP) yarns in the manufacture of semi-resorbable parietal implants. The goal of the present study consisted in assigning drug reservoir properties and prolonged antibacterial effect to a 100% PLLA knit through its functionalization with a cyclodextrin polymer (polyCD) and activation with ciprofloxacin. The study focused i) on the control of degree of polyCD functionalization of the PLLA support and on its physical and biological characterization by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC) and cell viability, ii) on the understanding of drug/meshes interaction using mathematic model and iii) on the correlation between drug release studies in phosphate buffer saline (PBS) and microbiological evaluation of meshes and release medium against E. coli and S. aureus. All above mentioned tests highlighted the contribution of polyCD on the improved performances of the resulting antibacterial implantable material. STATEMENT OF SIGNIFICANCE: 1. We managed for the first time, with well-defined parameters in terms of temperature and time of treatment, to functionalize a bio-absorbable synthetic material to improve drug sorption and drug release properties without affecting its mechanical properties. 2. We analyzed for the first time the degradation of our coating products by mass spectroscopy to show that only citrate and cyclodextrin residues (and glucose units) without any cytotoxicity are formed. 3. We managed to improve the mechanical properties of the PLA with the cyclodextrin polymer to form a composite. The assembly (cyclodextrin polymer and PLLA) remains biodegradable.

Visceral mesh modified with cyclodextrin for the local sustained delivery of ropivacaine.

The aim of the study was to develop a polyester visceral implant modified with a cyclodextrin polymer for the local and prolonged delivery of ropivacaine to reduce post operatory pain. Therefore, we applied a coating of an inguinal mesh with a crosslinked polymer of hydroxypropyl-ß-cyclodextrin (HPßCD) whose specific host-guest complex forming properties were expected to improve the adsorption capacity of the implant toward anesthetic, and then to release it within a sustained period. The modification reaction of the textile with cyclodextrin was explored through the study of the influence of the pad/dry/cure process parameters and the resulting implant (PET-CD) was characterized by solid state NMR and SEM. Besides, the inclusion complex between ropivacaine and CD was studied by NMR and capillary electrophoresis in PBS medium. Finally, ropivacaine sorption test showed that a maximum of 30 mg/g of ropivacaine could be adsorbed on the functionalized samples. In dynamic batch tests in PBS at pH 7.4, the release could be observed up to 6h. The cytocompatibility of the PET-CD loaded with ropivacaine was also studied and reached 65% cell vitality after 6 days.