Multilayer Tissue Model Research Articles

SLC37A4, gene responsible for glycogen storage disease type 1b, regulates gingival epithelial barrier function via JAM1 expression

Solute carrier family 37 member 4 (SLC37A4) is known to regulate glucose-6-phosphate transport from cytoplasm to the lumen of the endoplasmic reticulum, which serves to maintain glucose homeostasis. Glycogen storage disease type 1b (GSD1b) is caused by a mutation of SLC37A4, leading to a glycogenolysis defect. Although GSD1b cases are known to be complicated by periodontitis, the etiological molecular basis remains unclear. The present study investigated the effects of SLC37A4 on gingival barrier function. Examinations of immortalized human gingival epithelial (IHGE) cells showed SLC37A4 localized in the endoplasmic reticulum. SLC37A4 knockout decreased expression of JAM1, a tight junction-related protein, in IHGE cells. Using in silico analysis to investigate potential transcription factor binding sites, H6 family homeobox 3 (HMX3) was shown to be related to JAM1 expression. In HMX3-knockdown IHGE cells, JAM1 expression was markedly suppressed. Furthermore, HMX3 was scarcely detected in SLC37A4-knockout cells, while HMX3 overexpression restored JAM1 expression in those cells. Finally, using a three-dimensional multilayered gingival epithelial tissue model, knockout of SLC37A4 was also found to increase permeability to lipopolysaccharide and peptidoglycan, which was dependent on JAM1 expression. Specific downregulation of HMX3 by SLC37A4 and the consequent decrease in JAM1 expression provides findings indicating a molecular basis for the reduction in barrier function of gingival epithelial tissues in GSD1b cases.

Technical note: Computational study on thermal management schemes for tumor-treating fields therapy.

The study focuses on thermal management in tumor-treating fields (TTFields) therapy, crucial for patient compliance and therapeutic effectiveness. TTFields therapy, an established treatment for glioblastoma, involves applying alternating electric fields to the brain. However, managing the thermal effects generated by electrodes is a major challenge, impacting patient comfort and treatment efficiency. This research aims to explore methods for controlling temperature increases during TTFields therapy without reducing its duty cycle. The study emphasizes optimizing electrode configurations and array arrangements to mitigate temperature rise, thereby maintaining therapy effectiveness and patient compliance. Using a simplified multi-layer tissue model and finite element analysis, various electrode configurations and array shapes were tested in COMSOL Multiphysics v6.0. Adjustments included changing the electrode gel layer radius from 8 to 12mm, electrode spacing, and transitioning to a more uniform array arrangement, such as a square array or a circular array. The study revealed a strong correlation between high temperatures and edge current density distributions on electrodes. It was found that increasing the electrode gel layer's diameter, enlarging electrode spacing, and adopting a uniform array arrangement markedly mitigated temperature rises. By increasing the gel layer radius from the original 10 to 12mm, a reduction in the peak temperature increases of approximately 0.3°C was observed. Changing the layout from rectangular to circular with the same area further reduced the peak temperature rise by 0.5°C. Additionally, enlarging the spacing between electrodes also contributed to temperature control. By integrating these strategies, we designed a new circular electrode array with an electrode spacing of 45mm and a gel radius of 12mm, successfully reducing the peak temperature from 42.1°C to 40.8°C, effectively achieving temperature control. The research demonstrates that improving electrode and array configurations can effectively manage temperature in TTFields therapy without compromising treatment duration. This strategy is crucial as TTFields therapy relies on prolonged field exposure for effectiveness. The findings offer valuable insights into thermal management in electrode array design and could lead to enhanced patient compliance and treatment efficacy in TTFields therapy.

An implantable ISM band antenna for biomedical application

Abstract This article presents a compact implantable antenna for biomedical use in the ISM band (2.4–2.48 GHz). The antenna is designed with Roger RT/duroid 6010.2LM high permittivity substrate of thickness 0.25 mm, and feed with a 50 Ω co-axial feed. A hybrid-loop resonator slot structure and C & I-shaped slots in the radiating patch has enabled the antenna to work in the ISM band. Via less ground makes this design simple, easier to fabricate, and a suitable candidate for implantable application. The proposed antenna occupies a small volume of 0.0984 λ 0 × 0.082 λ 0 × 0.00468 λ 0 and retained 152 MHz bandwidth (2.4077–2.5599 GHz with FBW 7.64 %) with a maximum gain of −22 dBi where λ 0 is guided wavelength. The projected antenna has good performance in the multi-layer tissue model, male human head voxel model, frequency-dependent skin model, and in muscle phantom by maintaining a minimum −20 dB return-loss in the ISM band. The proposed antenna’s Device Integration using a frequency-dependent skin phantom was performed and the results are well-suited for biomedical applications in the ISM band. The bare antenna was used to study the Specific Absorption Rate (SAR) in the human scalp. Where for 1 g and 10 g tissues the investigated results are 626.05 W/kg and 84.4 W/kg for an input power of 1 W, however the input power is limited to maximum 2.55 mW (for 1 g tissue) and 23.56 mW (for 10 g tissue) to comply with IEEE SAR guidelines. The qualities of the manufactured antenna are verified in a skin-imitating gel and animal tissue that exhibits good agreement with the simulation outcomes.

Cigarette smoke extract impairs gingival epithelial barrier function

We previously showed that junctional adhesion molecule 1 (JAM1) and coxsackievirus and adenovirus receptor (CXADR), tight junction-associated proteins, have important roles to maintain epithelial barrier function in gingival tissues. Smoking is considered to be a significant risk factor for periodontal disease. The present study was conducted to examine the effects of cigarette smoke extract (CSE) on JAM1 and CXADR in human gingival epithelial cells. CSE was found to cause translocation of JAM1 from the cellular surface to EGFR-positive endosomes, whereas CXADR did not. Using a three-dimensional multilayered gingival epithelial tissue model, CSE administration was found to increase permeability to lipopolysaccharide and peptidoglycan, whereas overexpression of JAM1 in the tissue model prevented penetration by those substrates. Furthermore, vitamin C increased JAM1 expression, and inhibited penetration of LPS and PGN induced by CSE. These findings strongly suggest that CSE disrupts gingival barrier function via dislocation of JAM1, thus allowing bacterial virulence factors to penetrate into subepithelial tissues. Furthermore, they indicate that vitamin C increases JAM1 expression and prevents disruption of gingival barrier function by CSE.

Optimal design of electrodes for functional electrical stimulation applications to single layer isotropic tissues

PurposeThe purpose of this paper is to investigate the design of skin surface electrodes for functional electrical stimulation using an isotropic single layered model of the skin and underlying tissue. A concentric ring electrode geometry was analysed and compared with a conventional configuration, specifically to localise and maximise the activation at depth and minimise the peak current density at the skin surface.Design/methodology/approachThe mathematical formulation determines the spatial electric potential distribution in the tissue, using the solution to the Laplace equation in the lower half space subject to boundary conditions given by the complete electrode model and appropriate asymptotic decay. Hence, it is shown that the electric potential satisfies a weakly singular Fredholm integral equation of the second kind which is then solved numerically in MATLAB for a novel concentric ring electrode configuration and the conventional two disk side-by-side electrode configuration.FindingsIn both models, the electrode geometry can be optimised to obtain a higher activation and lower maximum current density. The concentric ring electrode configuration, however, provides improved performance over the traditional two disk side-by-side electrode configuration.Research limitations/implicationsIn this study, only a single layer of medium was investigated. A comparison with multilayer tissue models and in vivo validation of numerical simulations are required.Originality/valueThe developed mathematical approaches and simulations revealed the parameters that influence nerve activation and facilitated the theoretical comparison of the two electrode configurations. The concentric ring configuration potentially may have significant clinical advantages.

Theoretical analysis of photoacoustic effects in a multilayered skin tissue model

Due to its noninvasiveness, high resolution, and high sensitivity, photoacoustic imaging has developed rapidly in the field of biomedicine. However, research on dermatosis detection by photoacoustic imaging is still lacking. In this paper, the skin is modeled as a multilayer planar medium based on the non-homogeneous, complex layered structure of the skin tissue. Then, the analytical expression for the photoacoustic signal of multilayer skin tissue was derived under the assumption that the thermal and optical parameters of the skin tissue do not vary with temperature. The expression not only considers the influence of optical, thermal, and mechanical parameters of the tissue on the photoacoustic signal but also, for the first time, the influence of the number of skin layers on the photoacoustic signal. The analytical expression of the photoacoustic signal containing the number of skin layers is also given. The numerical simulation results show that the difference between the photoacoustic signal of the seven-layer skin model and the single-layer skin model is 15.206 × 10−6 MPa when ω = 3.5 MHz and μa = 2.70 cm−1. Therefore, the increase in the number of model layers enhances the amplitude of its photoacoustic signal. This work provides a comprehensive study of photoacoustic mechanisms in dermatosis tissues and establishes a theoretical foundation for the application of photoacoustic imaging detection technology in the diagnosis and treatment of dermatosis, which may improve treatment plans.

Assessing reliability and validity of different stiffness measurement tools on a multi-layered phantom tissue model

Changes in the mechanical properties (i.e., stiffness) of soft tissues have been linked to musculoskeletal disorders, pain conditions, and cancer biology, leading to a rising demand for diagnostic methods. Despite the general availability of different stiffness measurement tools, it is unclear as to which are best suited for different tissue types and the related measurement depths. The study aimed to compare different stiffness measurement tools’ (SMT) reliability on a multi-layered phantom tissue model (MPTM). A polyurethane MPTM simulated the four layers of the thoracolumbar region: cutis (CUT), subcutaneous connective tissue (SCT), fascia profunda (FPR), and erector spinae (ERS), with varying stiffness parameters. Evaluated stiffness measurement tools included Shore Durometer, Semi-Electronic Tissue Compliance Meter (STCM), IndentoPRO, MyotonPRO, and ultrasound imaging. Measurements were made by two independent, blinded examiners. Shore Durometer, STCM, IndentoPRO, and MyotonPRO reliably detected stiffness changes in three of the four MPTM layers, but not in the thin (1 mm thick) layer simulating FPR. With ultrasound imaging, only stiffness changes in layers thicker than 3 mm could be measured reliably. Significant correlations ranging from 0.70 to 0.98 (all p < 0.01) were found. The interrater reliability ranged from good to excellent (ICC(2,2) = 0.75–0.98). The results are encouraging for researchers and clinical practitioners as the investigated stiffness measurement tools are easy-to-use and comparatively affordable.

The princess and the pea - Comparison of different stiffness assessment tools on a multi-layered phantom tissue model

The princess and the pea - Comparison of different stiffness assessment tools on a multi-layered phantom tissue model

Assessment of Transmitted Power Density in the Planar Multilayer Tissue Model due to Radiation from Dipole Antenna

Recent relevant safety guidelines IEEE-Std C95.1- 2019 and ICNIRP-RF Guidelines 2020 have converged towards 6 GHz as a transition frequency from specific absorption rate (SAR), as basic restriction quantity, to absorbed power density (APD). Namely, the penetration of electromagnetic waves into the human tissue rapidly decreases as frequency increases, therefore, tissue heating can be considered as superficial above 6 GHz. However, besides the APD, an alternative internal dosimetric quantity transmitted power density or TPD is sometimes computed since its relation to SAR is more obvious and is easier to obtain. This paper deals with an analytical/numerical approach to determine TPD in planar multi-layered model of the human tissue exposed to the dipole antenna radiation. Analytical approach deals with assumed sinusoidal current distribution, while numerical approach pertains to the determination of current by solving the corresponding Pocklington integro-differential equation via Galerkin-Bubnov Indirect Boundary Element Method. The novelty presented in this paper with respect to previous work is a multilayer geometry whose effects are considered via the corresponding Fresnel plane wave reflection/transmission approximation. Some illustrative results for current distribution, transmitted field, volume power density (VPD) and TPD at various frequencies and distances of the antenna from the interface are given.

Modeling of a Compact Dual Band and Flexible Elliptical-Shape Implantable Antenna in Multi-Layer Tissue Model

A flexible antenna of compact size with a dual band elliptical-shape implantable is designed for biomedical purposes. The suggested antenna has an elliptical shape to be more comfortable for being implanted in human tissue. The implantable antenna is printed on RO3010 substrate with 2 mm as a thickness and 10.2 as a dielectric constant. It consists of an active planar C-shaped element and a parasitic planar inverted C-shaped element. The proposed antenna is designed with a major axis radius of 12 mm and a minor axis radius of 8 mm. It operates in dual bands: The Industrial Scientific and Medical band (ISM) [2.4 GHz–3.5 GHz] and Medical Implant Communications Service band (MICS) [394 MHz–407.61 MHz]. A short-circuited pin is used to minimize the antenna’s overall size and for further size reduction a capacitive load is used between the radiator and the ground plane. For biocompatibility, a thin-thickness layer of Alumina is used as a superstrate. The suggested antenna is tested in a multi-layer tissue model and the Specific Absorption Rate (SAR) value is computed. The proposed antenna was fabricated, and the reflection coefficient is measured and compared with simulated results.

Near-Reflectionless Wireless Transmission Into the Body With Cascaded Metasurfaces

The ability to transmit wireless signals into the body is important for medical communication, sensing, and powering technologies. However, the efficiency of signal transmission is limited by the large reflection encountered at the interface between air and biological tissue. Here, we demonstrate an approach to overcome this reflection using cascaded metasurfaces (MSs) with deeply subwavelength thickness to transform the wave impedance at the air–tissue interface. We develop a procedure to systematically synthesize these MSs using a multilayer tissue model that can account for different body compositions. Using this procedure, we design a three-layer MS operating at 2.45 GHz with <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\lambda /24.5$ </tex-math></inline-formula> thickness. Full-wave simulations in a computational human body model show that the MS provides transmission equivalent to replacing the background with a tissue-matched medium, while experimental measurements demonstrate 12.1 dB enhancement of transmission into a multilayer tissue phantom.

Perfusion culture of multi-layered HepG2 hepatocellular carcinoma cells in a pressure-driven microphysiological system

Here we report the perfusion culture of a multi-layered tissue composed of HepG2 cells (a human hepatoma line) in a pressure-driven microphysiological system (PD-MPS), which we developed previously as a multi-throughput perfusion culture platform. The perfusion culture of multi-layered tissue model was constructed by inserting a modified commercially available permeable membrane insert into the PD-MPS. HepG2 cells were layered on the membrane, and culture medium was perfused both through and below the membrane. The seeded density (number of cells/cm2) of the culture model is 70 times that of static culture in a conventional 35-mm culture dish. Pressure-driven circulation of the medium in our compact device (8.6× 7.0× 4.5cm3), which comprised two perfusion-culture modules and a pneumatic connection port, enabled perfusion culture of two multi-layered tissues (initially 1× 105cells). To obtain insight into the basic functionality of the multi-layered tissues as hepatocytes, we compared albumin production and urea synthesis between perfusion cultures and static cultures. The HepG2 cells grew and secreted increasing amounts of albumin throughout 20 days of perfusion culture, whereas albumin secretion did not increase under static culture conditions. In addition, on day 20, the amount of albumin secreted by the HepG2 cells in the microfluidic device was 68% of that in the conventional culture dish, which was seeded with the same number of cells but had a 70 times larger culture area. These features of high-density culture of functioning cells in a compact device support the application of PD-MPS in single- and multi-organ MPS.

Porphyromonas gingivalis Infection Induces Lipopolysaccharide and Peptidoglycan Penetration Through Gingival Epithelium.

Periodontal diseases initiate on epithelial surfaces of the subgingival compartment, while the gingival epithelium functions as an epithelial barrier against microbial infection and orchestrates immune responses. Porphyromonas gingivalis is a major pathogen of periodontal diseases and has an ability to penetrate the epithelial barrier. To assess the molecular basis of gingival epithelial barrier dysfunction associated with P. gingivalis, we newly developed a three-dimensional multilayered tissue model of gingival epithelium with gene manipulation. Using this novel approach, P. gingivalis gingipains including Arg- or Lys-specific cysteine proteases were found to specifically degrade junctional adhesion molecule 1 and coxsackievirus and adenovirus receptor in the tissue model, leading to increased permeability for lipopolysaccharide, peptidoglycan, and gingipains. This review summarizes the strategy used by P. gingivalis to disable the epithelial barrier by disrupting specific junctional adhesion molecules.

A computational multilayer model to simulate hollow needle insertion into biological porcine liver tissue

Modelling of needle insertion in soft tissue has developed significant interest in recent years due to its application in robot-assisted minimally invasive surgeries such as biopsies and brachytherapy. However, this type of surgery requires real-time feedback and processing which complex computational models may not be able to provide. In contrast to the existing mechanics-based kinetic models, a simple multilayer tissue model using a Coupled Eulerian Lagrangian based Finite Element method has been developed using the dynamic principle. The model simulates the needle motion for flexible hollow bevel-angled needle (15° and 30°, 22 Gauge) insertion into porcine liver tissue, which includes material parameters obtained from unconfined compression testing of porcine liver tissue. To validate simulation results, needle insertion force and cutting force within porcine liver tissue were compared with corresponding experimental results obtained from a custom-built needle insertion system. For the 15° and 30° bevel-angle needles, the percentage error for cutting force (mean) of each needle compared to computational model, were 18.7% and 11.9% respectively. Varying the needle bevel angle from 30° to 15° results in an increase of the cutting force, but insertion force does not vary among the tested bevel angles. The validation of this computationally efficient multilayer Finite Element model can help engineers to better understand the biomechanical behaviour of medical needle inside soft biological tissue. Ultimately, this multilayer approach can help advance state-of-art clinical applications such as robot-assisted surgery that requires real-time feedback and processing. Statement of significanceThe significance of the work is in confirming the effectiveness of multilayer material based finite element (FE) method to model biopsy needle insertion into soft biological porcine liver tissue. A multilayer Coupled Eulerian Lagrangian (CEL) based FE modelling technique allowed testing of heterogeneous, non-linear viscoelastic porcine liver tissue in a system, so direct comparison of needle tissue interaction forces on the intrinsic material (tissue) behaviour could be made. To the best of the authors’ knowledge, the present research investigates for the first time modelling of a three dimensional (3D) hollow needle insertion using a multilayer stiffness model of biological tissue using FE based CEL method and presents a comparison of simulation results with experimental data.

A new microfluidic method enabling the generation of multi-layered tissues-on-chips using skin cells as a proof of concept

Microfluidic-based tissues-on-chips (TOCs) have thus far been restricted to modelling simple epithelia as a single cell layer, but likely due to technical difficulties, no TOCs have been reported to include both an epithelial and a stromal component despite the biological importance of the stroma for the structure and function of human tissues. We present, for the first time, a novel approach to generate 3D multilayer tissue models in microfluidic platforms. As a proof of concept, we modelled skin, including a dermal and an epidermal compartment. To accomplish this, we developed a parallel flow method enabling the deposition of bilayer tissue in the upper chamber, which was subsequently maintained under dynamic nutrient flow conditions through the lower chamber, mimicking the function of a blood vessel. We also designed and built an inexpensive, easy-to-implement, versatile, and robust vinyl-based device that overcomes some of the drawbacks present in PDMS-based chips. Preliminary tests indicate that this biochip will allow the development and maintenance of multilayer tissues, which opens the possibility of better modelling of the complex cell–cell and cell–matrix interactions that exist in and between the epithelium and mesenchyme, allowing for better-grounded tissue modelling and drug screening.

Implantable Antenna Design Based on Gosper Curve Fractal Geometry

A Gosper curve fractal-based geometry novel Planar Inverted F-antenna (PIFA) antenna has been proposed for implantable biotelemetry applications. The antenna is designed to work inside the human muscle tissue at the MICS band (402–405 MHz). The antenna is composed of two layers of radiating patch stacked together on Rogers RO 3010 substrate with a thickness of 10 mil and a radius of 5 mm. The volumetric size of the proposed antenna is approximately 60 mm3. The initial antenna is designed inside the single layer human muscle tissue and optimized inside the multilayer tissue model. Furthermore, lumped equivalent circuit models, based on Bessel filter function, have been proposed and their results are analogized with the proposed antenna design with an error of 2.1%. The performance of fabricated antenna prototype inside human muscle, mimicking liquid phantom, is matched to a large extent closely to the proposed numerical antenna model that ensures its reliability.

Compact Broadband Planar Resonator With a Viaed Double Spiral for Robust Wireless Power Transfer

A common problem for most strongly coupled magnetic resonance (SCMR) wireless power transfer (WPT) systems is the dramatic efficiency drops by surrounding high-dielectric objects, e.g., people, caused by the narrow bandwidth of the systems due to a high quality factor ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$Q$</tex-math></inline-formula> ). In this paper, a compact broadband planar double-spiral resonator with a via is proposed to obtain a robust SCMR system with a stable efficiency where interference from high-dielectric surrounding objects is mitigated. The increased bandwidth is obtained without compromising power transfer efficiency by introducing coupling enhancement to the structure while <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$Q$</tex-math></inline-formula> is reduced. The bandwidth of the system is increased by over 15% compared to a conventional system with single-sided resonators, and the efficiency is comparable. In this paper, it is found that the location of the via affects both the efficiency and bandwidth of the SCMR system. Meanwhile, this paper reports an experiment with human hand phantom and a simulation study with multi-layered tissue model, both of which mimic a real human-involved environment, and successfully demonstrate the stability and high efficiency of power transfer of the proposed broadband resonators in a WPT system. Moreover, the proposed structure is tested to be less sensitive to misalignment between the transmitter and the receiver, and the proposed method is compared to the systems proposed for similar human-involved environments. This proposed viaed double-spiral resonator is a promising candidate for a robust WPT system for human-involved environments.

Viscoelastic model characterization of human cervical tissue by torsional waves

The understanding of changes in the viscoelastic properties of cervical tissue during the gestation process is a challenging problem. In this work, we explore the importance of considering the multilayer nature (epithelial and connective layers) of human cervical tissue for characterizing the viscoelastic parameters from torsional waves. For this purpose, torsional wave propagations are simulated in three multilayer cervical tissue models (pure elastic, Kelvin–Voigt (KV) and Maxwell) using the finite difference time domain method. High-speed camera measurements have been carried out in tissue-mimicking phantoms in order to obtain the boundary conditions of the numerical simulations. Finally, a parametric modeling study through a probabilistic inverse procedure was performed to rank the most plausible rheological model and to reconstruct the viscoelastic parameters. The procedure consist in comparing the experimental signals obtained in human cervical tissues using the Torsional Wave Elastography (TWE) technique with the synthetic signals from the numerical models. It is shown that the rheological model that best describes the nature of cervical tissue is the Kelvin–Voigt model. Once the most plausible model has been selected, the stiffness and viscosity parameters have been reconstructed of the epithelial and connective layers for the measurements of the 18 pregnant women, along with the thickness of the epithelial layer.

Preparation of Extracellular Matrix Paper and Construction of Multi-Layered 3D Tissue Model.

Construction of organized three-dimensional (3D) tissue with extracellular matrix (ECM) and multiple types of cells is important for tissue engineering to enable tissue function and enhance cellular function. However, the concentration of ECM and the thickness of the 3D tissue have been limited in previous methods due to a lack of permeability to nutrients and oxygen. Besides, it is difficult to use matured natural ECM as a cell scaffold without chemical modification due to its insolubility. In this article, we focus on multi-layered structure, which is commonly found in living tissue such as skin, blood vessels, and other organs. Here, we describe the preparation of a paper-like scaffold (ECM paper) from micro-fibered natural ECM and the construction of 3D multi-layered tissue composed of cell layers and ECM layers by stacking cell-seeded ECM papers. The thickness and components of the ECM layers are easily controllable by changing the composition of the ECM papers, and the fibrous structure of ECM paper shows high permeability and permits cell migration. Additionally, the ECM microfiber, which is physically defiberized from natural ECM, has a high ECM concentration equal to that of living tissue and high stability under physiological conditions. Therefore, this set of protocols enables construction of multi-layered 3D tissue composed of precisely controlled ECM layers and cell layers that may contribute to the assembly of tissue models. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Preparation of extracellular matrix paper Basic Protocol 2: Evaluation of cellular function of cells on extracellular matrix paper Basic Protocol 3: Construction of multi-layered 3D tissue.

Ultra-Miniature Circularly Polarized CPW-Fed Implantable Antenna Design and its Validation for Biotelemetry Applications

The paper presents a coplanar waveguide (CPW)-fed ultra-miniaturized patch antenna operating in Industrial, Scientific and Medical (ISM) band (2.4–2.5 GHz) for biotelemetry applications. The proposed antenna structure is circular in shape and its ground plane is loaded with a pair of slots for obtaining circular polarization. In the proposed design, asymmetric square slots generate phase condition for right-hand circularly polarized (RHCP) radiation. And, by merely changing the position of the slots, either RHCP or left-hand circularly polarized (LHCP) radiation can be excited. In the proposed design, a meandered central strip is used for miniaturization. The simulations of the proposed antenna are carried out using Ansys HFSS software with a single-layer and multilayer human tissue models. The antenna shows good performance for different tissue properties owing to its wide axial ratio bandwidth and impedance bandwidth. The antenna is fabricated and measurements are carried out in skin mimicking phantom and pork. Simulated and measured performances of the antenna are in close agreement. The power link budget is also calculated using an exterior circularly polarized (CP) receiving antenna.