Allometric tissue-scale forces activate mechanoresponsive immune cells to drive pathological foreign body response to biomedical implants

For decades, it has been assumed that the foreign body response (FBR) to biomedical implants is primarily a reaction to the chemical and mechanical properties of the implant. Here, we show for the first time that a third independent variable, allometric tissue-scale forces (which increase exponentially with body size), can drive the biology of FBR in humans. We first demonstrate that pathological FBR in humans is mediated by immune cell-specific Rac2 mechanotransduction signaling, independent of implant chemistry or mechanical properties. We then show that mice, which are typically poor models of human FBR, can be made to induce a strikingly human-like pathological FBR by altering these extrinsic tissue forces. Altering these extrinsic tissue forces alone activates Rac2 signaling in a unique subpopulation of immune cells and results in a human-like pathological FBR at the molecular, cellular, and local tissue levels. Finally, we demonstrate that blocking Rac2 signaling negates the effect of increased tissue forces, dramatically reducing FBR. These findings highlight a previously unsuspected mechanism for pathological FBR and may have profound implications for the design and safety of all implantable devices in humans.

A unique Thy-1-negative immuno-fibroblast population emerges as a key determinant of fibrotic outcomes to biomaterials

Microporous annealed particle (MAP) hydrogels are an exciting new development in biomaterial design. They regulate innate and acquired immunity which has been linked to their ability to evade normal host-material fibrosis. Yet, resident stromal fibroblasts, not immune cells, are the arbiters of the extracellular matrix assembly that characterizes fibrosis. In other idiopathic fibrotic disorders, a fibroblast subpopulation defined by its loss of cell surface Thy-1 expression is strongly correlated with degree of fibrosis. We have previously shown that Thy-1 is a critical αvβ3 integrin regulator that enables normal fibroblast mechanosensing and here, leveraging non-fibrosing MAP gels, we demonstrate that Thy-1-/- mice mount a robust response to MAP gels that remarkably resembles a classical foreign body response. We further find that within the naive, Thy-1+ fibroblast population exists a distinct and cryptic αSMA+ Thy-1- population that emerges in response to IL-1β and TNFα. Employing single-cell RNA sequencing, we find that IL-1β/TNFα-induced Thy-1- fibroblasts actually consist of two distinct subpopulations, both of which are strongly pro-inflammatory. These findings illustrate the emergence of a unique pro-inflammatory, pro-fibrotic fibroblast subpopulation that is central to material-associated fibrosis likely through amplifying local inflammatory signaling.

Covid-19 Vaccination Maternal Services for Pregnant Women in the Work Area of Telaga Community Health Centers

This study aims to provide an overview of how the covid-19 vaccination service for pregnant women in the work area of the Telaga Health Center. This study uses a qualitative method that focuses on ANC services with in-depth interview techniques, data analysis is carried out descriptively and presented in narrative form. This research was carried out in the working area of the Telaga Health Center from September 2021 to November 2022. The informants in this study were pregnant women in the Telaga Health Center working area as many as 7 participants and 2 key informants were the program coordinator midwives. With a snowball sampling technique. The results of the study found that there were 5 themes that described Covid-19 vaccination services for pregnant women, namely Socialization of Covid-19 Vaccination for pregnant women, Issue of KIPI for Covid-19 Vaccination, Supporting Factors for Successful Vaccination in Pregnant Women, Body Response of Pregnant Women after Covid-19 Vaccination. 19, and Covid-19 Vaccination Requirements for Pregnant Women. The mandatory output in this research is the publication of research results in one of the international journals.

Epidemiology, evaluation and management of tinea pedis

Tinea pedis, known as athletics foot, is defined as a dermatophyte infection leading to a condition called dermatophytosis. Usually, the mode of infection is fungal. Trichophyton rubrum is the most common organism which is responsible for the infection. This fungus is endemic in some geographical regions as in Asia and Africa. The mode of transmission and risk factors depends on several factors: the weather, type of clothes and shoes, body response to different organisms, present history, family history, and endemic geographical areas. Increased temperature and humidity were correlated in the literature to the increased incidence and prevalence of tinea pedis compared to those areas which have low temperature, wearing specific types of shoes or clothes might be associated with an increased rate of infection, especially if the shoes are adherent to the foot and occlusive, prolonged exposure to humidity and water was also shown to be among the causes for tinea pedis infections. The clinical presentation of tinea pods varies according to the site and severity of infection. Generally, antifungal drugs are effective in most cases. The application of antifungals may be in oral form or local form, or mixed form. Terbinafine was proven to be effective in mild cases to fully treat the infection within a period of one week, extending to four weeks in more aggressive cases. This was a brief look at the article. This article aimed to review tinea pedis from different prospections clinically.

Foreign Body Response and Intravital Microscopy on AIW in Mice

The foreign body response is the body’s response to the insertion of an object. The foreign body response consists of two components, the innate and adaptive immune response, and lasts for the life of the inserted object. Accordingly, the foreign body response represents a significant challenge to the development of implanted medical devices. In addition to triggering the damaging consequences of inflammation, the foreign body response acts to encapsulate and isolate inserted objects, limiting the functional lifetime of medical devices such as glucose monitors. Accordingly, significant efforts have been devoted to understanding the cell biology of the foreign body response to identify approaches for limiting surface “biofouling”. We have developed an indwelling window system that support longitudinal intravital microscopy of mice. In studies of transgenic mice expressing fluorescent immune cells, we found that the window triggers a local inflammatory response. To explore the utility of this window system as an experimental platform for characterizing the foreign body response, we conducted an intravital microscopy study of 8 mice expressing GFP in myeloid immune cells (Lys-EGFP mice) with surgically implanted abdominal imaging windows. To identify differences in the responses to different surface chemistries, the windows were either left uncoated or coated with poly-L-lysine or type V mouse collagen prior to insertion. Intravital multiphoton microscopy studies conducted over a period of up to 3 weeks demonstrated that the window instigated a local recruitment of immune cells, followed by vascularization and giant cell formation that varied depending upon window surface treatment. These studies demonstrate the utility of the abdominal window as a model system for studying the cell biology of the foreign body response and represent the template for subsequent studies designed to compare the foreign body response to different coating materials designed to extend the useful lifetime of implanted devices.

Key Regulatory Differentially Expressed Genes in the Blood of Atrial Septal Defect Children Treated With Occlusion Devices

Atrial septal defects (ASDs) are the most common types of cardiac septal defects in congenital heart defects. In addition to traditional therapy, interventional closure has become the main treatment method. However, the molecular events and mechanisms underlying the repair progress by occlusion device remain unknown. In this study, we aimed to characterize differentially expressed genes (DEGs) in the blood of patients treated with occlusion devices (metal or poly-L-lactic acid devices) using RNA-sequencing, and further validated them by qRT-PCR analysis to finally determine the expression of key mediating genes after closure of ASD treatment. The result showed that total 1,045 genes and 1,523 genes were expressed differently with significance in metal and poly-L-lactic acid devices treatment, respectively. The 115 overlap genes from the different sub-analyses are illustrated. The similarities and differences in gene expression reflect that the body response process involved after interventional therapy for ASDs has both different parts that do not overlap and the same part that crosses. The same portion of body response regulatory genes are key regulatory genes expressed in the blood of patients with ASDs treated with closure devices. The gene ontology enrichment analysis showed that biological processes affected in metal device therapy are immune response with CXCR4 genes and poly-L-lactic acid device treatment, and the key pathways are nuclear-transcribed mRNA catabolic process and proteins targeting endoplasmic reticulum process with ribosomal proteins (such as RPS26). We confirmed that CXCR4, TOB1, and DDIT4 gene expression are significantly downregulated toward the pre-therapy level after the post-treatment in both therapy groups by qRT-PCR. Our study suggests that the potential role of CXCR4, DDIT4, and TOB1 may be key regulatory genes in the process of endothelialization in the repair progress of ASDs, providing molecular insights into this progress for future studies.

Assessing the Effects of VEGF Releasing Microspheres on the Angiogenic and Foreign Body Response to a 3D Printed Silicone-Based Macroencapsulation Device

Macroencapsulation systems have been developed to improve islet cell transplantation but can induce a foreign body response (FBR). The development of neovascularization adjacent to the device is vital for the survival of encapsulated islets and is a limitation for long-term device success. Previously we developed additive manufactured multi-scale porosity implants, which demonstrated a 2.5-fold increase in tissue vascularity and integration surrounding the implant when compared to a non-textured implant. In parallel to this, we have developed poly(ε-caprolactone-PEG-ε-caprolactone)-b-poly(L-lactide) multiblock copolymer microspheres containing VEGF, which exhibited continued release of bioactive VEGF for 4-weeks in vitro. In the present study, we describe the next step towards clinical implementation of an islet macroencapsulation device by combining a multi-scale porosity device with VEGF releasing microspheres in a rodent model to assess prevascularization over a 4-week period. An in vivo estimation of vascular volume showed a significant increase in vascularity (* p = 0.0132) surrounding the +VEGF vs. −VEGF devices, however, histological assessment of blood vessels per area revealed no significant difference. Further histological analysis revealed significant increases in blood vessel stability and maturity (** p = 0.0040) and vessel diameter size (*** p = 0.0002) surrounding the +VEGF devices. We also demonstrate that the addition of VEGF microspheres did not cause a heightened FBR. In conclusion, we demonstrate that the combination of VEGF microspheres with our multi-scale porous macroencapsulation device, can encourage the formation of significantly larger, stable, and mature blood vessels without exacerbating the FBR.

Long-Term Evaluation of Poly(lactic acid) (PLA) Implants in a Horse: An Experimental Pilot Study

In horses, there is an increasing interest in developing long-lasting drug formulations, with biopolymers as viable carrier alternatives in addition to their use as scaffolds, suture threads, screws, pins, and plates for orthopedic surgeries. This communication focuses on the prolonged biocompatibility and biodegradation of PLA, prepared by hot pressing at 180 °C. Six samples were implanted subcutaneously on the lateral surface of the neck of one horse. The polymers remained implanted for 24 to 57 weeks. Physical examination, plasma fibrinogen, and the mechanical nociceptive threshold (MNT) were performed. After 24, 28, 34, 38, and 57 weeks, the materials were removed for histochemical analysis using hematoxylin-eosin and scanning electron microscopy (SEM). There were no essential clinical changes. MNT decreased after the implantation procedure, returning to normal after 48 h. A foreign body response was observed by histopathologic evaluation up to 38 weeks. At 57 weeks, no polymer or fibrotic capsules were identified. SEM showed surface roughness suggesting a biodegradation process, with an increase in the median pore diameter. As in the histopathological evaluation, it was not possible to detect the polymer 57 weeks after implantation. PLA showed biocompatible degradation and these findings may contribute to future research in the biomedical area.