Properties Of Biological Tissues Research Articles

The influence of pH and salt concentration on the microstructure and mechanical properties of meniscus extracellular matrix-derived implants.

Meniscus-related injuries are a common orthopedic challenge with an increasing incidence in the population. While the preservation of viable meniscal tissue is the preferred approach in repair strategies, complex or total traumatic lesions may require alternative therapeutic approaches such as meniscal reconstruction using allografts or engineered equivalents. Although clinical studies suggest promising outcomes with the use of acellular implants, further development is needed to improve their biological and mechanical requirements. Decellularized extracellular matrix (dECM) derived from menisci is a promising biomaterial for meniscus tissue engineering due to its recapitulation of the native tissue environment and the maintenance of tissue-specific cues. However, the associated mechanical limitations of dECM-derived scaffolds frequently impedes their adoption, requiring additional reinforcement or combining with stiffer biomaterials to increase their load-bearing properties. In this study, decellularized extracellular matrix was extracted and its fibrillation was controlled by adjusting both pH and salt concentrations to fabricate mechanically functional meniscal tissue equivalents. The effect of collagen fibrillation on the mechanical properties of the dECM constructs was assessed, and porcine-derived fibrochondrocytes were used to evaluate in vitro biocompatibility. It was also possible to fabricate meniscus-shaped implants by casting of the dECM and to render the implants suitable for off-the-shelf use by adopting a freeze-drying preservation method. Suture pull-out tests were also performed to assess the feasibility of using existing surgical methods to fix such implants within a damaged meniscus. This study highlights the potential of utilizing ECM-derived materials for meniscal tissue substitutes that closely mimic the mechanical and biological properties of native tissue.

One approach for selection of materials available for 3D printing of a dosimetry pelvic phantom: numerical simulation

Pelvic organ tumors are a serious problem in the field of oncology and account for one-third of the total number of the most common locations of neoplasms. Radiation therapy is often used to treat these types of cancer. A necessary procedure in the application of radiation therapy is the verification of the dosimetric plan to ensure maximum accuracy of radiation and minimize the negative effects of overexposure. To achieve these goals, dosimetry phantoms are used to mimic the structure and properties of biological tissues. Additive technologies can be an effective method for manufacturing such phantoms due to their high-precision ability to replicate both body geometry and anatomical structures. Today, the search and development of materials suitable for both additive technologies and assessing the interaction of ionizing radiation with matter is a relevant task. In this study, models of biological tissues and organs, as well as materials for 3D printing, were created. The features of Co-60 photon beam interaction with these materials were analyzed by numerical simulation. The calculated results demonstrated the suitability of plastic materials based on polylactide for simulating individual biological tissues and human organs from the point of view of interaction with ionizing radiation.

Study on the difference of high frequency dielectric properties of biological tissues measured by air and packed coaxial probe

In this paper, the differences between air probe and filled probe for measuring high-frequency dielectric properties of biological tissues are investigated based on the equivalent circuit model to provide a reference for the methodology of high-frequency measurement of biological tissue dielectric properties. Two types of probes were used to measure different concentrations of NaCl solution in the frequency band of 100 MHz-2 GHz. The results showed that the accuracy and reliability of the calculated results of the air probe were lower than that of the filled probe, especially the dielectric coefficient of the measured material, and the higher the concentration of NaCl solution, the higher the error. By laminating the probe terminal, liquid intrusion could be prevented, to a certain extent, to improve the accuracy of measurement. However, as the frequency decreased, the influence of the film on the measurement increased and the measurement accuracy decreased. The results of the study show that the air probe, despite its simple dimensional design and easy calibration, differs from the conventional equivalent circuit model in actual measurements, and the model needs to be re-corrected for actual use. The filled probe matches the equivalent circuit model better, and therefore has better measurement accuracy and reliability.

Using the stm32f407vg microcontroller to study the amplitude-frequency characteristics of biological tissues

The electrical properties of biological tissues of a plant origin are studied using the microcontroller STM32f407vg. The formulation of the problem of identifying informative signs of the viability of biological tissues when using the method of impedance measurement is given. It is shown that since currently in medical diagnostic practice there is no instrument base that would allow in an operational setting to diagnose the ability of biological tissue to self-heal after injury and damage as a result of thermal exposure, a gunshot wound or prolonged compression, the development of methods and means of instrumental diagnostics in this area of knowledge is an important modern task.
 The results of experimental measurements of impedance characteristics in the frequency range of 20 Hz – 2.0 MHz are presented. The frequency dependences of the stress modulus of a biological tissue of a plant origin are analyzed in its intact state, as well as after exposure of samples of a biological tissue in a freezer.
 A comparative analysis of the obtained frequency dependences is carried out. A significant difference between the frequency dependences of the stress modulus on a biological tissue and the frequency dependence of the stress modulus on an isotonic solution is shown. The idea was proposed that the degree of difference in the frequency distribution of the impedance module of the biological tissue from the impedance module of the isotonic solution can serve as a criterion for assessing the degree of damage to the biological tissue.

Custom Hyperspectral Imaging System Reveals Unique Spectral Signatures of Heart, Kidney, and Liver Tissues

The rapid advancement of diagnostic and therapeutic optical techniques for oncology demands a good understanding of the optical properties of biological tissues. This study explores the capabilities of hyperspectral (HS) cameras as a non-invasive and non-contact optical imaging system to distinguish and highlight spectral differences inbiological soft tissuesof three structures (kidney, heart, and liver) for use inendoscopic interventionoropen surgery. The study presents an optical system consisting of two individual setups, the transmission setup, and the reflection setup, both incorporating anHS camerawith apolychromatic light sourcewithin the range of 380 to 1050 nm to measure tissue's light transmission (Tr) and diffuse light reflectance (Rd), respectively. The optical system was calibrated with a customizedliquid optical phantom, then 30 samples from various organs were investigated fortissue characterizationby measuring both Tr and Rd at the visible and near infrared (VIS-NIR) band. We exploited the ANOVA test, subsequently by a Tukey's test on the created three independent clusters (kidney vs. heart: group I / kidney vs. liver: group II / heart vs. liver: group III) to identify the optimum wavelength for each tissue regarding their spectroscopic optical properties in the VIS-NIR spectrum. The optimum spectral span for the determined light Tr of the three groups was 640 ∼ 680 nm, and the ideal range was 720 ∼ 760 nm for the measured light Rd for mutual group I and group II. However, the group III range was different at a range of 520 ∼ 560 nm. Therefore, the investigation provides vital information concerning theoptimum spectral scalefor the computed light Tr and Rd of the investigatedbiological tissues(kidney, liver, and heart) to be employed in diagnostic andtherapeutic medical applications.

Dielectric Characterization of Breast Biopsied Tissues as Pre-Pathological Aid in Early Cancer Detection: A Blinded Feasibility Study.

Dielectric characterization has significant potential in several medical applications, providing valuable insights into the electromagnetic properties of biological tissues for disease diagnosis, treatment planning, and monitoring of therapeutic interventions. This work presents the use of a custom-designed electromagnetic characterization system, based on an open-ended coaxial probe, for discriminating between benign and malignant breast tissues in a clinical setting. The probe's development involved a well-balanced compromise between physical feasibility and its combined use with a reconstruction algorithm known as the virtual transmission line model (VTLM). Immediately following the biopsy procedure, the dielectric properties of the breast tissues were reconstructed, enabling tissue discrimination based on a rule-of-thumb using the obtained dielectric parameters. A comparative analysis was then performed by analyzing the outcomes of the dielectric investigation with respect to conventional histological results. The experimental procedure took place at Complejo Hospitalario Universitario de Toledo-Hospital Virgen de la Salud, Spain, where excised breast tissues were collected and subsequently analyzed using the dielectric characterization system. A comprehensive statistical evaluation of the probe's performance was carried out, obtaining a sensitivity, specificity, and accuracy of 81.6%, 61.5%, and 73.4%, respectively, compared to conventional histological assessment, considered as the gold standard in this investigation.

Structurally decoupled stiffness and solute transport in multi-arm poly(ethylene glycol) hydrogels

Synthetic hydrogels are widely used as artificial 3D environments for cell culture, facilitating the controlled study of cell-environment interactions. However, most hydrogels are limited in their ability to represent the physical properties of biological tissues because stiffness and solute transport properties in hydrogels are closely correlated. Resultingly, experimental investigations of cell-environment interactions in hydrogels are confounded by simultaneous changes in multiple physical properties. Here, we overcame this limitation by simultaneously manipulating four structural parameters to synthesize a library of multi-arm poly (ethylene glycol) (PEG) hydrogel formulations with robustly decoupled stiffness and solute transport. This structural design approach avoids chemical alterations or additions to the network that might have unanticipated effects on encapsulated cells. An algorithm created to statistically evaluate stiffness-transport decoupling within the dataset identified 46 of the 73 synthesized formulations as robustly decoupled. We show that the swollen polymer network model accurately predicts 11 out of 12 structure-property relationships, suggesting that this approach to decoupling stiffness and solute transport in hydrogels is fundamentally validated and potentially broadly applicable. Furthermore, the unprecedented control of hydrogel network structure provided by multi-arm PEG hydrogels confirmed several fundamental modeling assumptions. This study enables nuanced hydrogel design for uncompromised investigation of cell-environment interactions.

Microwave-Based Dielectric Properties as an Electrophysiological Biomarker: Future Perspectives

Electrophysiology is the study of the electrical properties of biological tissues, which involves the movement of ions across cell membranes. The analysis of the movement of electrical charges through the body has a wide range of biomedical applications, such as diagnosing and planning treatment in cardiovascular, nervous systems, muscular, and gastrointestinal disorders. The dielectric properties of biological tissues change according to the water content in the tissue and are measured as permittivity and conductivity relative to the frequency of the electrical field. This principle has been applied in diagnostics and therapeutics using microwave energysuch as imaging and ablation, etc. This review article summarizes the potential use of measuring dielectric properties using microwave imaging and how it can augment electrophysiological studies in medicine.

Measure of lung dielectric proprieties in patients with Idiopathic Pulmonary Fibrosis: correlation with clinical, radiological and pulmonary functional parameters

BackgroundDielectric properties of biological tissues are biophysical parameters; in lung they change with amount of air, blood and parenchyma. Remote Dielectric Sensing (ReDS™) technology measures dielectric properties of lung tissues quantifying the content of fluids inside the scan volume. We aimed to evaluate the reliability of ReDS™ measure in Idiopathic Pulmonary Fibrosis (IPF) patients and in healthy volunteers, and to investigate the correlation of ReDS™ score with clinical, radiological and functional parameters. MethodsWe conducted a prospective observational study, including 52 patients with diagnosis of IPF and 17 healthy volunteers; for each patient we recorded: complete functional evaluation, dyspnoea score (mMRC scale), Usual Interstitial Pneumonia (UIP) Computed Tomography (CT) pattern (UIP definite or probable) and ReDS™ measure (expressed in %). ResultsReDS™ measure was reported as correct both in patients and controls, the firsts with higher scores (33.8% vs 29.1%, p = 0.003). In IPF patients we observed a significant inverse correlation with ReDS™ score and Forced Vital Capacity (FVC), Vital Capacity (VC) and Total Lung Capacity (TLC) measures and, when we considered only patients with UIP definite CT pattern, the correlation was inverse with FVC, VC, TLC, DLCO. In IPF patients the higher was mMRC dyspnoea index, the higher was ReDS™ score. No significant correlations were observed between ReDS™ score and functional parameters in healthy controls. DiscussionWe demonstrated a correlation of ReDS™ scores with some functional (mainly indicative or diagnostic for restriction) and clinical parameters in IPF patients; the score was correlated with density of tissues possibly quantifying tissue fibrosis in IPF patients.

Characterization of renal fibrosis in rats with chronic kidney disease by in vivo tomoelastography.

Chronic kidney disease (CKD) is characterized by structural changes, such as tubular atrophy, renal fibrosis, and glomerulosclerosis, all of which affect the viscoelastic properties of biological tissues. However, detection of renal viscoelasticity changes because diagnostic markers by in vivo elastography lack histopathological validation through animal models. Therefore, we investigated in vivo multiparametric magnetic resonance imaging (mp-MRI), including multifrequency magnetic resonance elastography-based tomoelastography, in the kidneys of 10 rats with adenine-induced CKD and eight healthy controls. Kidney volume (in mm3 ), water diffusivity (apparent diffusion coefficient [ADC] in mm2 /s), shear wave speed (SWS; in m/s; related to stiffness), and wave penetration rate (PR; in m/s; related to inverse viscosity) were quantified by mp-MRI and correlated with histopathologically determined renal fibrosis (collagen area fraction [CAF]; in %). Kidney volume (40% ± 29%, p = 0.009), SWS (11% ± 12%, p = 0.016), and PR (20% ± 15%, p = 0.004) were significantly increased in CKD, which was accompanied by ADC (-24% ± 27%, p = 0.02). SWS, PR, and ADC were correlated with CAF with R = 0.63, 0.75, and -0.5 (all p < 0.05), respectively. In the CKD rats, histopathology showed tubule dilation due to adenine crystal deposition. Collectively, our results suggest that collagen accumulation during CKD progression transforms soft-compliant renal tissue into a more rigid-solid state with reduced water mobility. We hypothesized that tubule dilation-a specific feature of our model-might lead to higher intraluminal pressure, which could also contribute to elevated renal stiffness. Tomoelastography is a promising tool for noninvasively assessing disease progression, detecting biomechanical properties that are sensitive to different pathologic features of CKD.

A Rapid Stokes Imaging Method for Characterizing the Optical Properties of Tissue During Immersion Optical Clearing

The diffusion of drugs or agents in biological tissues is vital in biomedicine. Here we propose a non-invasive polarization optical method to evaluate the microstructural changes in tissues during agent diffusion. Skeletal muscle samples immersed in an aqueous solution of glycerol of various concentrations are taken to confirm the performance of the method. Temporal polarized images are captured by a rapid Stokes imaging system, then Stokes parameters <i>s</i>₁<i>, s</i>₂<i>, s</i>₃ are calculated and polarization parameters such as depolarization &#x0394;_c and linear retardance &#x03B4; are derived for quantifying tissue changes. By observing polarization parameters in experiments using different concentrations of agents, staged characteristics during tissue optical clearing are extracted. Comparing diffusion properties at different concentrations, we find that the variation of polarization parameters becomes more significant with the increasing concentration. Combined with Monte Carlo simulations, the dominant mechanism in different optical clearing stages in tissues can be explained. Specifically, dehydration dominates in the first stage, and refractive index matching gradually dominates after a transitional stage. The experiments and simulations confirm the potential of rapid Stokes imaging to explore the diffusion properties in biological tissues and give a detailed optical characterization and explanation.

Readily prepared and processed multifunctional MXene nanocomposite hydrogels for smart electronics

AbstractBooming sophisticated robotics and prosthetics put forward high requirements on soft conductive materials that can bridge electronics and biology, those soft conductive materials should imitate the mechanical properties of biological tissues and build information transmission networks. Until now, it remains a great challenge to handle the trade‐off among ease of preparation, high conductivity, processability, mechanical adaptability, and external stimuli responsiveness. Herein, a kind of readily prepared and processed multifunctional MXene nanocomposite hydrogel is reported, which is prepared via the fast gelation of cationic monomer initiated by delaminated MXene sheets. The gelation time can be adjusted (several seconds to minutes) based on the MXene loadings. By adjusting the MXene ratio, the resulting nanocomposites are ultrastretchable (&gt;5000%), three‐dimensional (3D) printable, and show outstanding mechanical and electrical self‐healing. As expected, the integration of multifunctional systems onto various substrates (e.g., gloves and masks) is further demonstrated via 3D printing and could achieve diverse sensory capabilities toward strain, pressure, and temperature, showing great prospects as smart flexible electronics.

Artificial neural network-based determination of denoised optical properties in double integrating spheres measurement

Accurate determination of the optical properties of biological tissues enables quantitative understanding of light propagation in these tissues for optical diagnosis and treatment applications. The absorption ([Formula: see text]) and scattering ([Formula: see text]) coefficients of biological tissues are inversely analyzed from their diffuse reflectance (R) and total transmittance (T), which are measured using a double integrating spheres (DIS) system. The inversion algorithms, for example, inverse adding doubling method and inverse Monte Carlo method, are sensitive to noise signals during the DIS measurements, resulting in reduced accuracy during determination. In this study, we propose an artificial neural network (ANN) to estimate [Formula: see text] and [Formula: see text] at a target wavelength from the R and T spectra measured via the DIS to reduce noise in the optical properties. Approximate models of the optical properties and Monte Carlo calculations that simulated the DIS measurements were used to generate spectral datasets comprising [Formula: see text], [Formula: see text], R and T. Measurement noise signals were added to R and T, and the ANN model was then trained using the noise-added datasets. Numerical results showed that the trained ANN model reduced the effects of noise in [Formula: see text] and [Formula: see text] estimation. Experimental verification indicated noise-reduced estimation from the R and T values measured by the DIS with a small number of scans on average, resulting in measurement time reduction. The results demonstrated the noise robustness of the proposed ANN-based method for optical properties determination and will contribute to shorter DIS measurement times, thus reducing changes in the optical properties due to desiccation of the samples.

Non-destructive Characterization of Skeletal Muscle Extracellular Matrix Morphology by Combining Optical Coherence Tomography (OCT) Imaging with Tissue Clearing.

Histology is an essential step to visualize and analyze the microstructure of any biological tissue; however, histological processing is often irreversible, and histological samples are unable to be imaged or tested further. In this work, a novel non-destructive protocol is proposed for morphological analysis of skeletal muscles, combining Optical Coherence Tomography (OCT) imaging with Tissue Clearing. Imaging combining OCT and Propylene Glycol (PG) as a tissue-clearing agent, was performed on rat tail and extensor digitorum longus (EDL) muscle. The results show that the extracellular matrix morphology of skeletal muscles, including muscular fibers and the whole microstructure architecture were clearly identified. PG improved OCT imaging as measured by image quality metric Contrast Per Pixel CPP (increases by 3.9%), Naturalness Image Quality Evaluator NIQE (decreases by 23%), and Volume of Interest VOI size (higher for CPP and lower for NIQE values). The tendon microstructure was observed with less precision, as collagen fibers could not be clearly detected. The reversibility of the optical effects of the PG on the immersed tissue (in a Phosphate-Buffered Saline solution) was studied comparing native and rehydrated OCT image acquisition from a single EDL sample. Optical properties and microstructure visibility (CPP and NIQE) have been recovered to 99% of the native sample values. Moreover, clearing process caused shrinkage of the tissue recovered to 86% of the original width. Future work will aim to employ the proposed experimental protocol to identify the local mechanical properties of biological tissues.

In situ sensing physiological properties of biological tissues using wireless miniature soft robots.

Implanted electronic sensors, compared with conventional medical imaging, allow monitoring of advanced physiological properties of soft biological tissues continuously, such as adhesion, pH, viscoelasticity, and biomarkers for disease diagnosis. However, they are typically invasive, requiring being deployed by surgery, and frequently cause inflammation. Here we propose a minimally invasive method of using wireless miniature soft robots to in situ sense the physiological properties of tissues. By controlling robot-tissue interaction using external magnetic fields, visualized by medical imaging, we can recover tissue properties precisely from the robot shape and magnetic fields. We demonstrate that the robot can traverse tissues with multimodal locomotion and sense the adhesion, pH, and viscoelasticity on porcine and mice gastrointestinal tissues ex vivo, tracked by x-ray or ultrasound imaging. With the unprecedented capability of sensing tissue physiological properties with minimal invasion and high resolution deep inside our body, this technology can potentially enable critical applications in both basic research and clinical practice.

DEVELOPMENT OF MR-BASED PROCEDURES FOR THE IMPLEMENTATION OF PATIENT-SPECIFIC DIELECTRIC MODELS FOR CLINICAL USE

Nowadays, many medical techniques are based on the application of electromagnetic fields (EMF) on human body. For the optimization of these techniques, it is necessary to understand the mechanisms of interaction between the biological system under exposure and the applied EMF. Since this interaction is described by the dielectric properties of the biological system, an accurate dielectric characterization of human body is necessary. Biological tissues are complex and heterogeneous, and their dielectric properties can vary significantly from the ex-vivo to the in vivo condition. For this reason, there is the need to measure these properties for a specific subject. Unfortunately, traditional techniques used to measure dielectric properties of tissues are not able to reach this aim and an alternative method must be devised. In this work, a model is proposed for the reconstruction of dielectric properties of biological tissues from MR acquisitions. This model is wideband, specific, applicable in vivo and useful for those medical techniques that need a precise dielectric characterization of the patients.

Spatial frequency domain imaging for the assessment of scleroderma skin involvement.

Systemic sclerosis (SSc) is an autoimmune disease characterized by the widespread deposition of excess collagen in the skin and internal organs, as well as vascular dysfunction. The current standard of care technique used to quantify the extent of skin fibrosis in SSc patients is the modified Rodnan skin score (mRSS), which is an assessment of skin thickness based on clinical palpation. Despite being considered the gold standard, mRSS testing requires a trained physician and suffers from high inter-observer variability. In this study, we evaluated the use of spatial frequency domain imaging (SFDI) as a more quantitative and reliable method for assessing skin fibrosis in SSc patients. SFDI is a wide-field and non-contact imaging technique that utilizes spatially modulated light to generate a map of optical properties in biological tissue. The SFDI data were collected at six measurement sites (left and right forearms, hands, and fingers) of eight control subjects and ten SSc patients. mRSS were assessed by a physician, and skin biopsies were collected from subject's forearms and used to assess for markers of skin fibrosis. Our results indicate that SFDI is sensitive to skin changes even at an early stage, as we found a significant difference in the measured optical scattering () between healthy controls and SSc patients with a local mRSS score of zero (no appreciable skin fibrosis by gold standard). Furthermore, we found a strong correlation between the diffuse reflectance (Rd) at a spatial frequency of 0.2 mm-1 and the total mRSS between all subjects (Spearman correlation coefficient = -0.73, p-value < 0.0028), as well as high correlation with histology results. The healthy volunteer results show excellent inter- and intra-observer reliability (ICC > 0.8). Our results suggest that the measurement of tissue and Rd at specific spatial frequencies and wavelengths can provide an objective and quantitative assessment of skin involvement in SSc patients, which could greatly improve the accuracy and efficiency of monitoring disease progression and evaluating drug efficacy.

Mechanical properties and failure mechanisms of polyamide 12 gradient scaffolds developed with selective laser sintering

Developing a functional gradient scaffold compatible with the fantastic biological and mechanical properties of natural bone tissue is imperative in bone tissue engineering. In this work, the stretch-dominated (cubical and circular) and bending-dominant (diamond and gyroid) pore styles were employed to design custom-graded scaffolds based on the curve interference method and then were fabricated by selective laser sintering (SLS) using polyamide 12 (PA12) powder. Subsequently, the mechanical behavior, failure mechanism, and energy absorption performance of porous structures were investigated via compression experiments and finite element (FE) simulation. The results indicated that the stretch-dominated radial gradient structures entire exhibited transverse shear failure and the bending-dominant radial gradient structures whole exhibited progressive destruction, while all of the axial gradient scaffolds suffered a predictable layer-by-layer fracture. Among them, the bending-dominated radial gradient structure of gyroid had been proven to sustain stronger deformability and energy absorption capacity. Meanwhile, the FE method powerfully predicted the mechanical behavior of the scaffold, and this research thereby possessed significant implications for the development of bone tissue engineering.

Microscopic single-pixel polarimetry for biological tissue

Single-pixel imaging (SPI) is a computational imaging modality that reconstructs images from information collected with a single-pixel detector. Due to the relatively large bandwidth and cheap price of single-pixel detectors over pixel-array detectors, SPI has been demonstrated with great success in many imaging scenarios. In this work, we further extended SPI to microscopic Mueller-matrix polarimetry, which is capable of providing polarization-sensitive properties of biological tissue with a millimeter-size field of view and micrometer-size resolution. As a proof of concept, we applied polarimetry on normal and cancerous esophagus tissues from patients and reconstructed their Mueller matrices. Effects of depolarization, retardation, and diattenuation were also examined by decomposing Mueller matrices. We envision that the developed computational technique can bring new possibilities for both SPI and Mueller-matrix polarimetry.

Recent Advances in Organ-on-Chips Integrated with Bioprinting Technologies for Drug Screening.

Currently, the demand for more reliable drug screening devices has made scientists and researchers develop novel potential approaches to offer an alternative to animal studies. Organ-on-chips are newly emerged platforms for drug screening and disease metabolism investigation. These microfluidic devices attempt to recapitulate the physiological and biological properties of different organs and tissues using human-derived cells. Recently, the synergistic combination of additive manufacturing and microfluidics has shown a promising impact on improving a wide array of biological models. In this review, different methods are classified using bioprinting to achieve the relevant biomimetic models in organ-on-chips, boosting the efficiency of these devices to produce more reliable data for drug investigations. In addition to the tissue models, the influence of additive manufacturing on microfluidic chip fabrication is discussed, and their biomedical applications are reviewed.