RESUMEN
The design of novel biomaterials should directly influence the host-immune system and steer it towards high biocompatibility. To date, new implants/materials have been tested for biocompatibility in vitro in cell cultures and in vivo in animal models. The current methods do not reflect reality (cell cultures) or are very time-consuming and deliver results only after weeks (animal model). In this proof-of-concept study, the suitability of a Whole Blood Stimulation Assay (WBSA) in combination with a Protein Profiler Array (PPA), as a readily available and cost-effective screening tool, was investigated. Three different biomaterials based on poly(lactic-co-glycolic acid (PLGA), calcium sulphate/-carbonate (CS) and poly(methyl methacrylate) (PMMA) were exposed to native whole blood from three volunteers and subsequently screened with a PPA. Individual reproducible protein profiles could be detected for all three materials after 24 h of incubation. The most intense reaction resulted from the use of PLGA, followed by CS. If even marginal differences in implants can be reflected in protein profiles, the combination of WBSA and PPA could serve as an early biocompatibility screening tool in the development of novel biomaterials. This may also lead to a reduction in costs and the amount of animal testing required.
RESUMEN
Polyethylene mimics of semicrystalline polyphosphoesters (PPEs) with an adjustable amount of noncovalent cross-links were synthesized. Acyclic diene metathesis copolymerization of a phosphoric acid triester (M1) with a novel phosphoric acid diester monomer (M2) was achieved. PPEs with different co-monomer ratios and 0, 20, 40, and 100% of phosphodiester content were synthesized. The phosphodiester groups result in supramolecular interactions between the polymer chains, with the P-OH functionality as an H-bond donor and the P=O group as an H-bond acceptor. A library of unsaturated and saturated PPEs was prepared and analyzed in detail by NMR spectroscopy, size exclusion chromatography, differential scanning calorimetry, thermogravimetry, rheology, and stress-strain measurements. The introduction of the supramolecular cross-links into the aliphatic and hydrophobic PPEs showed a significant impact on the material properties: increased glass-transition and melting temperatures were observed and an increase in the storage modulus of the polymers was achieved. This specific combination of a flexible aliphatic backbone and a supramolecular H-bonding interaction between the chains was maximized in the homopolymer of the phosphodiester monomer, which featured additional properties, such as shape-memory properties, and polymer samples could be healed after cutting. The P-OH groups also showed a strong adhesion toward metal surfaces, which was used together with the shape-memory function in a model device that responds to a temperature stimulus with shape change. This systematic variation of phosphodiesters/phosphotriesters in polyethylene mimics further underlines the versatility of the phosphorus chemistry to build up complex macromolecular architectures.
RESUMEN
Two-stage revision arthroplasty is the treatment of choice for periprosthetic infection, a serious complication after knee or hip arthroplasty. Our prospective clinical trial aimed to investigate the concentrations of gentamicin and vancomycin in wound exudate and tissue in two-stage revision arthroplasty. Wound exudate and periprosthetic membrane samples were collected from 18 patients (10 hip and eight knee patients), who were due for two-stage treatment after a periprosthetic joint infection. Samples were taken during insertion of antibiotic-impregnated spacers and after their removal. The concentrations of gentamicin and vancomycin in wound exudates and adjacent tissue were analyzed using high-performance liquid chromatography mass spectrometry. Average time period of spacer implantation was 13.6 weeks (9.3-22.6 weeks). The concentration of vancomycin in wound exudate decreased from a median of 43.28 µg/mL (0.28-261.22) after implantation to 0.46 µg/mL (0.13-37.47) after the removal of the spacer. In the adjacent tissue, vancomycin concentration was mainly undetectable prior to spacer implantation (0.003 µg/g [0.003-0.261]) and increased to 0.318 µg/g [0.024-484.16] at the time of spacer removal. This was also observed for gentamicin in the tissue of patients who previously had cement-free implants (0.008 µg/g [0.008-0.087] vs. 0.164 µg/g [0.048-71.75]) while in the tissue of patients with previously cemented prosthesis, baseline concentration was already high (8.451 µg/g [0.152-42.926]). Despite the rapid decrease in antibiotics release from spacer cement observed in vitro, in vivo antibiotics are much longer detectable, especially in the adjacent soft tissue. © 2018 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials Published By Wiley Periodicals, Inc. J Biomed Mater Res B Part B, 2019. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1587-1597, 2019.
