Person:

Villiger, Martin

Achieving significant adhesion to soft tissues while minimizing tissue damage poses a considerable clinical challenge. Chemical-based adhesives require tissue-specific reactive chemistry, typically inducing a significant inflammatory response. Staples are fraught with limitations including high-localized tissue stress and increased risk of infection, and nerve and blood vessel damage. Here, inspired by the endoparasite Pomphorhynchus laevis which swells its proboscis to attach to its host’s intestinal wall, we have developed a biphasic microneedle array that mechanically interlocks with tissue through swellable microneedle tips, achieving ~ 3.5 fold increase in adhesion strength compared to staples in skin graft fixation, and removal force of ~ 4.5 N/cm2 from intestinal mucosal tissue. Comprising a poly(styrene)-block-poly(acrylic acid) swellable tip and non-swellable polystyrene core, conical microneedles penetrate tissue with minimal insertion force and depth, yet high adhesion strength in their swollen state. Uniquely, this design provides universal soft tissue adhesion with minimal damage, less traumatic removal, reduced risk of infection and delivery of bioactive therapeutics.

Identifying tumour margins during breast-conserving surgeries is a persistent challenge. We have previously developed miniature needle probes that could enable intraoperative volume imaging with optical coherence tomography. In many situations, however, scattering contrast alone is insufficient to clearly identify and delineate malignant regions. Additional polarization-sensitive measurements provide the means to assess birefringence, which is elevated in oriented collagen fibres and may offer an intrinsic biomarker to differentiate tumour from benign tissue. Here, we performed polarization-sensitive optical coherence tomography through miniature imaging needles and developed an algorithm to efficiently reconstruct images of the depth-resolved tissue birefringence free of artefacts. First ex vivo imaging of breast tumour samples revealed excellent contrast between lowly birefringent malignant regions, and stromal tissue, which is rich in oriented collagen and exhibits higher birefringence, as confirmed with co-located histology. The ability to clearly differentiate between tumour and uninvolved stroma based on intrinsic contrast could prove decisive for the intraoperative assessment of tumour margins.

Background: DM remains a risk factor for poor outcome after stent-implantation, but little is known if and how DM affects the vascular response to BVS. Aim The aim of our study was to examine coronary responses to bioresorbable vascular scaffolds (BVS) in swine with and without diabetes mellitus fed a ‘fast-food’ diet (FF-DM and FF-NDM, respectively) by sequential optical coherence tomography (OCT)-imaging and histology. Methods: Fifteen male swine were evaluated. Eight received streptozotocin-injection to induce DM. After 9 months (M), 32 single BVS were implanted in epicardial arteries with a stent to artery (S/A)-ratio of 1.1:1 under quantitative coronary angiography (QCA) and OCT guidance. Lumen, scaffold, neointimal coverage and composition were assessed by QCA, OCT and near-infrared spectroscopy (NIRS) pre- and/or post-procedure, at 3M and 6M. Additionally, polarization-sensitive (PS)-OCT was performed in 7 swine at 6M. After sacrifice at 3M and 6M, histology and polymer degradation analysis were performed. Results: Late lumen loss was high (~60%) within the first 3M after BVS-implantation (P<0.01 FF-DM vs. FF-NDM) and stabilized between 3M and 6M (<5% change in FF-DM, ~10% in FF-NDM; P>0.20). Neointimal coverage was highly heterogeneous in all swine (DM vs. NDM P>0.05), with focal lipid accumulation, irregular collagen distribution and neointimal calcification. Likewise, polymer mass loss was low (~2% at 3M, ~5% at 6M;P>0.20) and not associated with DM or inflammation. Conclusion: Scaffold coverage showed signs of neo-atherosclerosis in all FF-DM and FF-NDM swine, scaffold polymer was preserved and the vascular response to BVS was not influenced by diabetes.

Owing to their electromagnetic properties, tunability and biocompatibility, gold nanorods (GNRs) are being investigated as multifunctional probes for a range of biomedical applications. However, detection beyond the reach of traditional fluorescence and two-photon approaches and quantitation of their concentration in biological tissue remain challenging tasks in microscopy. Here we show how the size and aspect ratio that impart GNRs with their plasmonic properties also make them a source of entropy. We report on how depolarization can be exploited as a strategy to visualize GNR diffusion and distribution in biologically relevant scenarios ex vivo, in vitro and in vivo. We identify a deterministic relation between depolarization and nanoparticle concentration. As a result, some of the most stringent experimental conditions can be relaxed, and susceptibility to artefacts is reduced, enabling microscopic and macroscopic applications.

Conventional thermal therapy monitoring techniques based on temperature are often invasive, limited by point sampling, and are indirect measures of tissue injury, while techniques such as magnetic resonance and ultrasound thermometry are limited by their spatial resolution. The visualization of the thermal coagulation zone at high spatial resolution is particularly critical to the precise delivery of thermal energy to epithelial lesions. In this work, an integrated thulium laser thermal therapy monitoring system was developed based on complex differential variance (CDV), which enables the 2D visualization of the dynamics of the thermal coagulation process at high spatial and temporal resolution with an optical frequency domain imaging system. With proper calibration to correct for noise, the CDV-based technique was shown to accurately delineate the thermal coagulation zone, which is marked by the transition from high CDV upon heating to a significantly reduced CDV once the tissue is coagulated, in 3 different tissue types ex vivo: skin, retina, and esophagus. The ability to delineate thermal lesions in multiple tissue types at high resolution opens up the possibility of performing microscopic image-guided procedures in a vast array of epithelial applications ranging from dermatology, ophthalmology, to gastroenterology and beyond.

Hypertrophic scars remain a major clinical problem in the rehabilitation of burn survivors and lead to physical, aesthetic, functional, psychological, and social stresses. Prediction of healing outcome and scar formation is critical for deciding on the best treatment plan. Both subjective and objective scales have been devised to assess scar severity. Whereas scales of the first type preclude cross-comparison between observers, those of the second type are based on imaging modalities that either lack the ability to image individual layers of the scar or only provide very limited fields of view. To overcome these deficiencies, this work aimed at developing a predictive model of scar formation based on polarization sensitive optical frequency domain imaging (PS-OFDI), which offers comprehensive subsurface imaging. We report on a linear regression model that predicts the size of a scar 6 months after third-degree burn injuries in rats based on early post-injury PS-OFDI and measurements of scar area. When predicting the scar area at month 6 based on the homogeneity and the degree of polarization (DOP), which are signatures derived from the PS-OFDI signal, together with the scar area measured at months 2 and 3, we achieved predictions with a Pearson coefficient of 0.57 (p < 10−4) and a Spearman coefficient of 0.66 (p < 10−5), which were significant in comparison to prediction models trained on randomly shuffled data. As the model in this study was developed on the rat burn model, the methodology can be used in larger studies that are more relevant to humans; however, the actual model inferred herein is not translatable. Nevertheless, our analysis and modeling methodology can be extended to perform larger wound healing studies in different contexts. This study opens new possibilities for quantitative and objective assessment of scar severity that could help to determine the optimal course of therapy.