Elke Van De Walle

Polydopamine-Gelatin as Universal Cell-Interactive Coating for Methacrylate-Based Medical Device Packaging Materials: When Surface Chemistry Overrules Substrate Bulk Properties.

Despite its widespread application in the fields of ophthalmology, orthopedics, and dentistry and the stringent need for polymer packagings that induce in vivo tissue integration, the full potential of poly(methyl methacrylate) (PMMA) and its derivatives as medical device packaging material has not been explored yet. We therefore elaborated on the development of a universal coating for methacrylate-based materials that ideally should reveal cell-interactivity irrespective of the polymer substrate bulk properties. Within this perspective, the present work reports on the UV-induced synthesis of PMMA and its more flexible poly(ethylene glycol) (PEG)-based derivative (PMMAPEG) and its subsequent surface decoration using polydopamine (PDA) as well as PDA combined with gelatin B (Gel B). Successful application of both layers was confirmed by multiple surface characterization techniques. The cell interactivity of the materials was studied by performing live-dead assays and immunostainings of the cytoskeletal components of fibroblasts. It can be concluded that only the combination of PDA and Gel B yields materials possessing similar cell interactivities, irrespective of the physicochemical properties of the underlying substrate. The proposed coating outperforms both the PDA functionalized and the pristine polymer surfaces. A universal cell-interactive coating for methacrylate-based medical device packaging materials has thus been realized.

First step toward near-infrared continuous glucose monitoring: in vivo evaluation of antibody coupled biomaterials.

Continuous glucose monitoring (CGM) is crucial in diabetic care. Long-term CGM systems however require an accurate sensor as well as a suitable measuring environment. Since large intravenous sensors are not feasible, measuring inside the interstitial fluid is considered the best alternative. This option, unfortunately, has the drawback of a lag time with blood glucose values. A good strategy to circumvent this is to enhance tissue integration and enrich the peri-implant vasculature. Implants of different optically transparent biomaterials (poly(methyl-methacrylate) [PMMA] and poly(dimethylsiloxane) [PDMS]) – enabling glucose monitoring in the near-infrared (NIR) spectrum – were surface-treated and subsequently implanted in goats at various implantation sites for up to 3 months. The overall in vivo biocompatibility, tissue integration, and vascularization at close proximity of the surfaces of these materials were assessed. Histological screening showed similar tissue reactions independent of the implantation site. No significant inflammation reaction was observed. Tissue integration and vascularization correlated, to some extent, with the biomaterial composition. A modification strategy, in which a vascular endothelial-cadherin antibody was coupled to the biomaterials surface through a dopamine layer, showed significantly enhanced vascularization 3 months after subcutaneous implantation. Our results suggest that the developed strategy enables the creation of tissue interactive NIR transparent packaging materials, opening the possibility of continuous glucose monitoring.

Cell response of flexible PMMA-derivatives: supremacy of surface chemistry over substrate stiffness

The present work reports on the development of a range of poly(methyl methacrylate)/poly(ethylene glycol) (PMMAPEG)-based materials, characterized by different elasticity moduli in order to study the influence of the substrate’s mechanical properties on the response of human umbilical vein endothelial cells (HUVECs). To render the selected materials cell-interactive, a polydopamine (PDA)/gelatin type B (Gel B) coating was applied. Prior to the in vitro assay, the success of the PDA and Gel B immobilization onto the materials was confirmed using X-ray photoelectron spectroscopy (XPS) as reflected by the nitrogen percentages measured for the materials after PDA and Gel B deposition. Tensile tests showed that materials with E-moduli ranging from 37 to 1542 MPa could be obtained by varying the ratio between PMMA and PEG as well as the PEG molecular weight and its functionality (i.e. mono-methacrylate vs. di-methacrylate). The results after 1 day of cell contact suggested a preferred HUVECs cell growth onto more rigid materials. After 1 week, the material with the lowest E-modulus of 37 MPa showed lower cell densities compared to the other materials. No clear correlation could be observed between the number of focal adhesion points and the substrate stiffness. Although minor differences were found, these were not statistically significant. This last conclusion again highlights the universal character of the PDA/Gel B modification. The present work could thus be valuable for the development of a range of cell substrates requiring different mechanical properties in line with the envisaged application while the cell response should ideally remain unaffected.Graphical abstract