Development of a Novel Valve-Controlled Drug-Elutable Microstent for Microinvasive Glaucoma Surgery: In Vitro and Preclinical In Vivo Studies.

Purpose: Microinvasive glaucoma surgery (MIGS) has become an important treatment approach for primary open-angle glaucoma, although the safe and long-term effective lowering of intraocular pressure with currently available implants for MIGS is not yet achieved to a satisfactory extent. The study focusses on the development and in vitro and in vivo testing of a novel microstent for MIGS. Methods: A silicone elastomer-based microstent was developed. Implants were manufactured using dip coating, fs-laser cutting, and spray coating. Within the current study no antifibrotic drug was loaded into the device. Sterilized microstents were analyzed in vitro regarding pressure-flow characteristics and biocompatibility. Six New Zealand white rabbits were implanted with a microstent draining the aqueous humor from the anterior chamber into the subconjunctival space. Drainage efficacy was evaluated using oculopressure tonometry as a transient glaucoma model. Noninvasive imaging was performed. Results: Microstents were manufactured successfully and characterized in vitro. Implantation in vivo was successful for four animals with additional device fixation. Without additional fixation, dislocation of microstents was found in two animals. Safe and effective intraocular pressure reduction was observed for the four eyes with correctly implanted microstent during the 6-month trial period. Conclusions: The described microstent represents an innovative treatment approach for MIGS. The incorporation of a selectively antifibrotic drug into the microstent drug-elutable coating will be addressed in future investigations. Translational Relevance: The current preclinical study successfully provided proof of concept for our microstent for MIGS which is suitable for safe and effective intraocular pressure reduction and offers promising perspectives for the clinical management of glaucoma.

An optimized 3D-printed perfusion bioreactor for homogeneous cell seeding in bone substitute scaffolds for future chairside applications.

A clinical implementation of cell-based bone regeneration in combination with scaffold materials requires the development of efficient, controlled and reproducible seeding procedures and a tailor-made bioreactor design. A perfusion system for efficient, homogeneous, and rapid seeding with human adipogenic stem cells in bone substitute scaffolds was designed. Variants concerning medium inlet and outlet port geometry, i.e. cylindrical or conical diffuser, cell concentration, perfusion mode and perfusion rates were simulated in silico. Cell distribution during perfusion was monitored by dynamic [18F]FDG micro-PET/CT and validated by laser scanning microscopy with three-dimensional image reconstruction. By iterative feedback of the in silico and in vitro experiments, the homogeneity of cell distribution throughout the scaffold was optimized with adjustment of flow rates, cell density and perfusion properties. Finally, a bioreactor with a conical diffusor geometry was developed, that allows a homogeneous cell seeding (hoover coefficient: 0.24) in less than 60 min with an oscillating perfusion mode. During this short period of time, the cells initially adhere within the entire scaffold and stay viable. After two weeks, the formation of several cell layers was observed, which was associated with an osteogenic differentiation process. This newly designed bioreactor may be considered as a prototype for chairside application.

Assessment of the Efficacy of Microinvasive Glaucoma Surgery Techniques using an Oculopression Stress Test. / Nicht invasiver Belastungstest zur Funktionsprüfung von mikroinvasiven Glaukomdrainage-Implantaten und Laserchirurgie.

BACKGROUND: Glaucoma is one of the most common causes of blindness worldwide. The only evidence-based treatment to slow down the progression of glaucoma is the reduction of intraocular pressure (IOP) using local medication or through surgery. During the last years, a large number of microinvasive glaucoma surgery techniques (MIGS) has been developed, in order to reduce the IOP in glaucoma patients safely and effectively. Until now, efficacy of MIGS has been assessed mainly according to the postoperative IOP and the number of medications used. Results from long-term studies are rare or not available in the majority of the cases. In order to better evaluate the functionality of MIGS, a new examination method has been developed with the help of a new oculopressor device. In this study the efficacy of different MIGS techniques will be examined using the new oculopressor. MATERIAL/METHODS: At first, glaucoma patients that had previously received a MIGS surgery (iStent inject, XEN Stent, ELT) were examined with the new oculopression test. Their results were compared with those of non-operated patients and healthy individuals. Overall, 38 healthy subjects (group 1), 10 non-operated patients (group 2), 19 patients after iStent inject implantation (group 3), 14 patients after XEN Stent implantation (group 4) and 5 patients after ELT (group 5) were examined. The new examination measures the IOP-reduction that occurs after oculopression and can be seen as an indirect measurement of the outflow facility of the eye. RESULTS: The IOP-reduction after oculopression differed among the study groups. Non-operated patients showed a significantly lower IOP-reduction compared to healthy individuals. Patients after iStent inject and XEN stent implantation showed a larger reduction of IOP after oculopression in relation to non-operated patients and their results approximated those of healthy individuals. These patients needed fewer medications postoperatively in relation to non-operated patients. Patients after ELT showed postoperatively a smaller reduction of IOP after oculopression compared to iStent inject and XEN stent patients. CONCLUSION: MIGS can increase the outflow facility of the eye in patients with glaucoma. Though ELT had the lowest impact on the aqueous outflow among the studied procedures in this study. The new test can help in the evaluation of current and further development of new MIGS in the future.