Development of a biodegradable microstent for minimally invasive treatment of Fallopian tube occlusions

Obstructions of the Fallopian tube represent one of the most common reasons for an unfulfilled desire to have children. Microstent technology opens up new therapeutic possibilities to restore the natural lumen of the Fallopian tube within a single treatment. Within the current work we developed a self-expandable biodegradable microstent for gynecological applications. Based on a novel microstent design, prototypes were manufactured from poly-L-lactide tubing by means of fs-laser cutting. Microstent prototypes were characterized morphologically by means of scanning electron microscopy and biaxial laser scanning. As manufactured, a microstents outside diameter of about 2.3 mm and a strut thickness/width of about 114 µm/103 µm was measured. Mechanical characterization of microstents included bending as well as crimping and release behavior. After crimping to a minimum diameter of 0.8 mm and consecutive release, a microstent recovery to a diameter of 1.8 mm was found. Therefore, proof-of-concept for the self-expandable microstent could be successfully provided. © 2020 by Walter de Gruyter Berlin/Boston 2020

Functional transformation series and the evolutionary origin of novel forms: evidence from a remarkable termite defensive organ

The origins of evolutionary novelties are often deeply puzzling. They are generally associated with new functions that were absent in ancestors. The new functional configuration should arise via intermediate stages without any loss of function or impediment to the whole organism during the transitions. Therefore, understanding of the functional configurations of transitional states can shed light on how novel forms arise. Here we infer the evolutionary origin of a highly specialized termite defensive organ "nasus" where different functions overlap in different structural configurations at intermediate evolutionary stages to ensure that each phase is functional. Soldiers of a nasutitermitine termite use reconfigured mandibular muscles to squirt a viscous secretion from a nozzle-like head projection (the nasus). This contrasts sharply with the primitive defensive strategy where mandibles are used to bite. MicroCT observations of soldiers of Nasutitermes takasagoensis and of species with the ancestral state (Hodotermopsis sjostedti, Embiratermes neotenicus) revealed three different yet fully functional configurations in the transition from ancestral to novel state: (i) elevated hydrostatic pressure induced by contraction of mandibular muscles when biting gently oozes secretion from a gland; (ii) direct pressure on an enlarged gland arises from expansion of the mandibular muscles when biting; (iii) squirting in a piston-like manner by an inflated gland enveloped by highly modified mandibular muscles. Even a structure as exotic as the nasus therefore appears to have evolved with no loss of function at any stage. Such a functional approach, holds much promise for understanding the evolutionary origin of seemingly preposterous novel forms

First 3D reconstruction of the rhizocephalan root system using MicroCT

Parasitic barnacles (Cirripedia: Rhizocephala) are highly specialized parasites of crustaceans. Instead of an alimentary tract for feeding they utilize a system of roots, which infiltrates the body of their hosts to absorb nutrients. Using X-ray micro computer tomography (MicroCT) and computer-aided 3D-reconstruction, we document the spatial organization of this root system, the interna, inside the intact host and also demonstrate its use for morphological examinations of the parasites reproductive part, the externa. This is the first 3D visualization of the unique root system of the Rhizocephala in situ, showing how it is related to the inner organs of the host. We investigated the interna from different parasitic barnacles of the family Peltogastridae, which are parasitic on anomuran crustaceans. Rhizocephalan parasites of pagurid hermit crabs and lithodid crabs were analysed in this study

Human Femoral Vein Diameter and Topography of Valves and Tributaries: A Post Mortem Analysis

Keiler J, Schulze M, Claassen H, Wree A. Human Femoral Vein Diameter and Topography of Valves and Tributaries: A Post Mortem Analysis. Clinical Anatomy. 2018;31(7):1065-1076.The femoral vein (FV) is a clinically important vessel. Failure of its valves can lead to chronic venous insufficiency (CVI) with severe manifestations such as painful ulcers. Although they are crucial for identifying suitable implant sites for therapeutic valves, studies on the topography of FV tributaries and valves are rare. Moreover, the femoral vein diameter (FVD) must be known to assess the morphometric requirements for valve implants. To reassess the anatomical requirements for valve implants, 155 FVs from 82 human corpses were examined. FVDs and tributary and valve topographies were assessed using a laboratory straightedge. The FVD increased from 6 mm in the distal femoropopliteal vein to 11 mm in the iliofemoral vein proximal to the saphenofemoral junction (SFJ). Diameters were significantly bigger in males than females. Height correlated positively with FVD. Distal to the SFJ, within a distance of 38 cm, one to eight valves were present. Up to two valves were present within 10 cm proximal to the SFJ. Individual tributary and valve topography must be considered to ensure appropriate design and successful implantation of a venous valve for CVI therapy in the FV. A suitable implant site would be proximal to the SFJ via an infrainguinal transfemoral access

Supplemental material for The femoral vein diameter and its correlation with sex, age and body mass index – An anatomical parameter with clinical relevance

<p>Supplemental material for The femoral vein diameter and its correlation with sex, age and body mass index – An anatomical parameter with clinical relevance by Jonas Keiler, Ronald Seidel and Andreas Wree in Phlebology</p

Fast and reliable dissection of porcine parathyroid glands — A protocol for molecular and histological analyses

As calcium and phosphorus are of vital importance for life, physiological activity of the parathyroid glands (PTGs) is crucial to maintain mineral homeostasis and bone mineralization. However, PTG-specific molecular routes in response to environmental factors and intrinsic hormonal responses are not yet fully understood. Since nutrient requirements, pathophysiology and functional genomics of pigs are similar to those of humans, pigs might be a suitable model to study the holistic gene expression and physiological aspects of the parathyroid gland, which could be used in both animal sciences and biomedical research. However, due to their small size and hidden location, the dissection of the PTGs, particularly in pigs, is difficult. Therefore, a protocol for untrained dissectors has been established that allows a fast and reliable identification of the PTGs in domestic pigs. Based on their localization within the cranial thymus near the carotid bifurcation, sampling was verified by histological staining and mRNA expression pattern. Analyses revealed the prominence of parathyroid hormone (PTH)-producing chief cells. Moreover, the copy numbers of PTH differed substantially between the PTGs and their surrounding thymus tissue, as PTH was expressed virtually exclusively in the PTGs. The developed protocol will substantially facilitate a fast and reliable dissection of porcine PTGs which is essential for studies characterizing the molecular mechanisms of parathyroid glands, e.g. when applying new feeding strategies in pigs

Development of an in vitro measurement method for improved assessment of the side branch expansion capacity

The expansion capacity and accessibility of the side branch is essential for the stenting of complex bifurcations. Since previous measurement methods only provide limited information based on geometrical data of stent cells, a new measurement approach was developed which considers the mechanical deformation capacity of the stent design. This approach provides essential information on the stent with regard to the application of bifurcation stenting. Four different commercially available coronary stents (nominal diameter 3.0 mm) were dilated and a central strut cell was over-expanded by means balloon catheters of increasing nominal diameter (2.0 to 5.0 mm). After balloon inflation, the remaining cell size was investigated for maximum cell diameter and strut fractures. Large expansion capacity without cell damage is taken as a measure of the accessibility of the side branch. In none of the expansion experiments the desired target size could be achieved, which is due to the elastic recoil of the stent cells. Deviations from the target diameter between 14-38% were determined. However, larger diameters also showed a constriction of the balloon, so that in some cases the target diameter could not be achieved at all. No strut fractures occurred even at maximum balloon diameter and pressure (5.0 mm noncompliant balloons). As a result the side branch accessibility differs depending on the individual stent designs. No particular risk for the stent was found by extensive overdilatation

Hemodynamic influence of design parameters of novel venous valve prostheses

Venous ulcers of the lower limbs are one clinical manifestation of chronic venous insufficiency. Currently, there is no venous valve prosthesis available. This study presents novel venous valve prostheses made of threedimensional electrospun fibrous nonwoven leaflets. The aim of this study was to prove the feasibility of the manufacturing process as well as to investigate design features of the venous valve prostheses from a hemodynamic point of view. An adapted pulse duplicator system (ViVitrolabs, Victoria, BC, CA) was used for characterization of the hydrodynamic performance. For eight different venous valve prototypes flow rate, effective orifice area and regurgitation fraction was investigated in vitro. In particular, tricusp valve designs showed an up to 40% higher effective orifice area as well as 15% higher maximum flowrate compared to bicusp valve designs. However, the regurgitation fraction of the bicusp valve designs is up to 86% lower compared to tricusp valve. Additionally, the hemodynamic performance of the tricuspid valves showed a high sensitivity regarding the leaflet length. Bicuspid valves are less sensitive to changes of design parameters, more sufficient and therefore highly reliable

Numerical simulation of a transcatheter aortic heart valve under application-related loading

For the treatment of severe symptomatic aortic valve stenosis, minimally invasive heart valve prostheses have more recently become the lifesaving solution for elderly patients with high operational risk and thus, are often implanted in patients with challenging aortic root configuration. A correct prosthesis deployment and stent adaption to the target region is essential to ensure optimal leaflet performance and long-term prosthesis function. The objective of this study was the development of a suitable in silico setup for structural numerical simulation of a transcatheter aortic valve (TAV) in different cases of clinical relevance. A transcatheter valve prosthesis comprising an unpressurized trileaflet heart valve and an adapted stent configuration was designed. An aortic root (AR) model was developed, based on microcomputed tomography of a native healthy specimen. Using the finite-element analysis (FEA), various loading cases including prosthesis biomechanics with valve opening and closing under physiological pressure ratios throughout a cardiac cycle, prosthesis crimping as well as crimping and release into the developed AR model were simulated. Hyperelastic constitutive law for polymeric leaflet material and superelasticity of shape memory alloys for the self-expanding Nitinol stent structure were implemented into the FEA setup. Calculated performance of the valve including the stent structure demonstrated enhanced leaflet opening and closing as a result of stent deformation and redirected loading. Crimping and subsequent release into the AR model as well as the stent adaption to the target region after expansion proved the suitability of the TAV design for percutaneous application. FEA represented a useful tool for numerical simulation of an entire minimally invasive heart valve prosthesis in relevant clinical scenarios