Karolien Gellynck

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.

Near-infrared bulk optical properties of goat wound tissue and human serum: consequences for an implantable optical glucose sensor

Near-infrared (NIR) spectroscopy offers a promising technological platform for continuous glucose monitoring in the human body. Moreover, these measurements could be performed in vivo with an implantable single-chip based optical sensor. However, a thin tissue layer may grow in the optical path of the sensor. As most biological tissues are highly scattering, they only allow a small fraction of the collimated light to pass, significantly reducing the light throughput. To quantify the effect of a thin tissue layer in the optical path, the bulk optical properties of serum and tissue samples grown on implanted dummy sensors were characterized using double integrating sphere and unscattered transmittance measurements. The estimated bulk optical properties were then used to calculate the light attenuation through a thin tissue layer. The combination band of glucose was found to be the better option, relative to the first overtone band, as the absorptivity of glucose molecules is higher, while the reduction in unscattered transmittance due to tissue growth is less. Additionally, as the wound tissue was found to be highly scattering, the unscattered transmittance of the tissue layer is expected to be very low. Therefore, a sensor configuration which measures the diffuse transmittance and/or reflectance instead was recommended. (a) Dummy sensor; (b) explanted dummy sensor in tissue lump; (c) removal of dummy sensor from tissue lump; and (d) 900 µm slices of tissue lump.

Ex vivo optical characterization of in vivo grown tissues on dummy sensor implants using Double Integrating Spheres measurement

Near infrared spectroscopy offers a promising technological platform for continuous glucose monitoring in the human body. NIR measurements can be performed in vivo with an implantable single-chip based optical NIR sensor. However, the application of NIR spectroscopy for accurate estimation of the analyte concentration in highly scattering biological systems still remains a challenge. For instance, a thin tissue layer may grow in the optical path of the sensor. As most biological tissues allow only a small fraction of the collimated light to pass, this might result in a large reduction of the light throughput. To quantify the effect of presence of a thin tissue layer in the optical path, the bulk optical properties of tissue samples grown on sensor dummies which had been implanted for several months in goats were characterized using Double Integrating Spheres and unscattered transmittance measurements. The measured values of diffuse reflectance, diffuse transmittance and collimated transmittance were used as input to Inverse Adding-Doubling algorithm to estimate the bulk optical properties of the samples. The estimates of absorption and scattering coefficients were then used to calculate the light attenuation through a thin tissue layer. Based on the lower reduction in unscattered transmittance and higher absorptivity of glucose molecules, the measurement in the combination band was found to be the better option for the implantable sensor. As the tissues were found to be highly forward scattering with very low unscattered transmittance, the diffuse transmittance measurement based sensor configuration was recommended for the implantable glucose sensor.