Samad Ahadian

Several microfabrication technologies have been used to engineer native‐like muscle tissues. However, the successful development of muscle remains a significant challenge in the tissue engineering field. Muscle tissue engineering aims to combine muscle precursor cells aligned within a highly organized 3D structure and biological factors crucial to...

Aerogel‐based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite e...

Within the complex microarchitecture of native cartilage tissue, the micromechanical properties of pericellular and extracellular matrices (PCM and ECM) potentially play important roles in developmental, physiological, and pathological processes. Here, we report a unique biomaterial-based engineering strategy to create cartilage-tissue equivalents...

Engineered nanostructures are innovative and precisely designed, synthesized, and tailored with outstanding physicochemical properties that can be applied as the game-changer in neural tissue engineering. The present study aimed to develop an innovative approach based on electrical stimulation through a conductive scaffold to differentiate neural c...

Thrombin is a serine protease with an essential role in homeostasis and blood coagulation. During vascular injuries, thrombin is generated from prothrombin, a plasma protein, to polymerize fibrinogen molecules into fibrin filaments. Moreover, thrombin is a potent stimulant for platelet activation, which causes blood clots to prevent bleeding. The r...

Blood–Brain Barrier Models In article number 2201401, Mehmet Remzi Dokmeci, Ali Khademhosseini, and co‐workers discuss recent progress and key applications of blood–brain barrier (BBB)‐on‐a‐chip and delineate potential future directions.

The human brain and central nervous system (CNS) present unique challenges in drug development for neurological diseases. One major obstacle is the blood–brain barrier (BBB), which hampers the effective delivery of therapeutic molecules into the brain while protecting it from blood‐born neurotoxic substances and maintaining CNS homeostasis. For BBB...

Microneedles (MNs) have been developed as minimally invasive tools for diagnostic and therapeutic applications. However, in recent years, there has been an increasing interest in developing smart multifunctional MN devices to provide automated and closed‐loop systems for body fluid extraction, biosensing, and drug delivery in a stimuli‐responsive m...

The cover image is based on the Research Article Coaxial 3Dbioprinting of tri‐polymer scaffolds to improve by Samad Ahadian et al., https://doi.org/10.1002/jbm.a.37354.

The eye is one of the most complex organs in the human body, containing rich and critical physiological information (e.g., intraocular pressure, corneal temperature, and pH) as well as a library of metabolite biomarkers (e.g., glucose, proteins, and specific ions). Smart contact lenses (SCLs) can serve as a wearable intelligent ocular prosthetic de...

Electrical stimulation can facilitate wound healing with high efficiency and limited side effects. However, current electrical stimulation devices have displayed poor conformability and coupling with wounds, due to their bulky nature and the rigidity of electrodes utilized. Here, a flexible electrical patch (ePatch) made with conductive hydrogel as...

Characterizing the mechanical properties of engineered tissue constructs provides powerful insight into the function of engineered tissues for their desired application. Current methods of mechanical characterization of soft hydrogels used in tissue engineering are often destructive and ignore the effect of 3D bioprinting on the overall mechanical...

Silk fibroin (SF) is a promising biomaterial for tendon repair, but its relatively rigid mechanical properties and low cell affinity have limited its application in regenerative medicine. Meanwhile, gelatin‐based polymers have advantages in cell attachment and tissue remodeling but have insufficient mechanical strength to regenerate tough tissue su...

Background: Tissue engineering provides various strategies to fabricate an appropriate microenvironment to support the repair and regeneration of lost or damaged tissues. In this matter, several technologies have been implemented to construct close-to-native three-dimensional structures at numerous physiological scales, which are essential to conf...

Electrical impulse generation and its conduction within cells or cellular networks are the cornerstone of electrophysiology. However, the advancement of the field is limited by sensing accuracy and the scalability of current recording technologies. Here we describe a scalable platform that enables accurate recording of transmembrane potentials in e...

Droplet-based microfluidic systems have been employed to manipulate discrete fluid volumes with immiscible phases. Creating the fluid droplets at microscale has led to a paradigm shift in mixing, sorting, encapsulation, sensing, and designing high throughput devices for biomedical applications. Droplet microfluidics has opened many opportunities in...

The crosstalk between osteoblasts and endothelial cells is critical for bone vascularization and regeneration. Here, we used a coaxial 3D bioprinting method to directly print an osteon-like structure by depositing angiogenic and osteogenic bioinks from the core and shell regions of the coaxial nozzle, respectively. The bioinks were made up of gelat...

Tissue engineering is an emerging area in medical sciences due to its advantages over organ transplantation. A successful TE requires appropriate biomaterial scaffolds, ideal cells, and growth mediators along with advanced regenerative technologies. An array of innovative technologies is being designed and demonstrated in advanced TE applications a...

Coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global burden to public health that manifests various symptoms, including self-limiting upper respiratory disorder, severe pneumonia, multi-organ failure, and even death. Thus, efficient approaches to tackle the rapid biological...

Injectable shear-thinning biomaterials (STBs) have attracted significant attention because of their efficient and localized delivery of cells as well as various molecules ranging from growth factors to drugs. Recently, electrostatic interaction-based STBs, including gelatin/LAPONITE® nanocomposites, have been developed through a simple assembly pro...

Wearable piezoresistive sensors are being developed as electronic skins (E‐skin) for broad applications in human physiological monitoring and soft robotics. Tactile sensors with sufficient sensitivities, durability, and large dynamic ranges are required to replicate this critical component of the somatosensory system. Multiple micro/nanostructures,...

Increasing evidence from cancer cell fusion with different cell types in the tumor microenvironment has suggested a probable mechanism for how metastasis-initiating cells could be generated in tumors. Although human mesenchymal stem cells (hMSCs) have been known as promising candidates to create hybrid cells with cancer cells, the role of hMSCs in...

Multifunctional Microcarriers In article number 2103192, Mohsen Akbari and co-workers engineer multifunctional microcarriers for high-throughput cell culture. These microcarriers support cell growth, can locally deliver biomolecules such as growth factors to the attached cells, and allow for subsequent cell harvesting via altered environmental temp...

Wearable piezoresistive sensors are being developed as electronic skins (e-skin) for broad applications in human physiological monitoring and soft robotics. Tactile sensors with sufficient sensitivities, durability, and large dynamic ranges are required to replicate this critical component of the somatosensory system. Multiple micro-/nano-structure...

Over the decades, researchers have strived to synthesize and modify nature-inspired biomaterials, with the primary aim to address the challenges of designing functional biomaterials for regenerative medicine and tissue engineering. Among these challenges, biocompatibility and cellular interactions have been extensively investigated. Some of the mos...

An effective treatment of human diseases using regenerative medicine and cell therapy approaches requires a large number of cells. Cultivation of cells on microcarriers is a promising approach due to the high surface‐to‐volume ratios that these microcarriers offer. Here, multifunctional temperature‐responsive microcarriers (cytoGel) made of an inte...

The remarkable ability of biological systems to sense and adapt to complex environmental conditions has inspired new materials and novel designs for next-generation wearable devices. Hydrogels are being intensively investigated for their versatile functions in wearable devices due to their superior softness, biocompatibility, and rapid stimuli-resp...

Tissue reconstruction requires the utilization of multiple biomaterials and cell types to replicate the delicate and complex structure of native tissues. Various three-dimensional (3D) bioprinting techniques have been developed to fabricate customized tissue structures; however, there are still significant challenges, such as vascularization, mecha...

Research in the development of ophthalmic drug formulations and innovative technologies over the past few decades has been directed at improving the penetration of medications delivered to the eye. Currently, approximately 90% of all ophthalmic drug formulations (e.g. liposomes, micelles) are applied as eye drops. The major challenge of topical eye...

Viral infection is one of the leading causes of mortality worldwide. The growth of globalization significantly increases the risk of virus spreading, making it a global threat to future public health. In particular, the ongoing coronavirus disease 2019 (COVID‐19) pandemic outbreak emphasizes the importance of devices and methods for rapid, sensitiv...

Mechanical deformation of human skin provides essential information about human motions, muscle stretching, vocal fold vibration, and heart rates. Monitoring these activities requires the measurement of strains at different levels. Herein, we report a wearable wide-range strain sensor based on conducting polymer poly(3,4-ethylenedioxythiophene) pol...

The COVID-19 pandemic continues to spread globally at a rapid pace, and its rapid detection remains a challenge due to its rapid infectivity and limited testing availability. One of the simply available imaging modalities in clinical routine involves chest X-ray (CXR), which is often used for diagnostic purposes. Here, we proposed a computer-aided...

Injectable Biomaterials In article number 2000113, Ali Khademhosseini, Samad Ahadian, and co-workers use biocompatible graphene quantum dots for imaging a physically crosslinked and injectable shear-thinning biomaterial of gelatin hydrogel and silicate nanoplatelets. The biomaterial shows a robust and stable fluorescence signal in vitro and in anim...

Research in the development of ophthalmic drug formulations and innovative technologies over the past few decades has been directed at improving the penetration of medications delivered to the eye. Currently, approximately 90% of all ophthalmic drug formulations (e.g. liposomes, micelles) are applied as eye drops. The major challenge of topical eye...

Organ-on-a-chip (OoC) models are bioengineered tissue constructs integrated with microfluidics that recapitulate the key features of the physiology of human organs and tissues with applications related to drug development and personalized medicine. The characterization of OoCs relies on conventional labor-intensive approaches despite the many years...

The efficiency of injectable biomaterials as minimally invasive therapeutics significantly relies on biomaterial’s characteristics, such as stability, biodegradation rate, and interaction with the host tissue, which requires real‐time tracking of the biomaterials. Fluorescence imaging is considered a non‐invasive technique for monitoring biomateria...

Smart contact lenses have emerged as novel wearable devices. Due to their multifunctional biosensing capabilities and highly integrated performance, they provide a great platform for the diagnosis of eye diseases and the delivery of drugs. Herein, a brief history of the development of contact lenses is given. Then, the state‐of‐the‐art design and f...

Treatment of skin injuries is still facing major challenges, such as chronicity and infections, particularly those caused by multi-drug resistance pathogens. An effective treatment of such wounds should accelerate the wound healing process while preventing bacterial contamination. Here, a novel core-shell nanofiber mat was fabricated comprising gel...

Cutaneous leishmaniasis (CL) is a significant public health problem caused by different species of Leishmania parasites. Due to low skin permeability, the development of an effective system for delivery of Amphotericin B (AMB), the common effective drug for leishmaniasis treatment, is required to replace the unpleasant and problematic injections. T...

Smart Contact Lenses Smart contact lenses are highly integrated devices with multifunctional capabilities for the diagnosis of eye diseases and the delivery of drugs. In article number 2000263, Samad Ahadian, Ali Khademhosseini, and co-workers present a brief history of the development of contact lenses and the state-of-the-art design and fabricati...

The skin serves a substantial number of physiological purposes and is exposed to numerous biological and chemical agents owing to its large surface area and accessibility. Yet, current skin models are limited in emulating the multifaceted functions of skin tissues due to a lack of effort on the optimization of biomaterials and techniques at differe...

Early diagnosis of breast cancer unequivocally improves the survival rate of patients and is crucial for disease treatment. With the current developments in infrared imaging, breast screening using dynamic thermography seems to be a great complementary method for clinical breast examination (CBE) prior to mammography. In this study, we propose a sp...

In article number 2007425, Junmin Lee, Ali Khademhosseini, and co‐workers present a breakthrough for modeling of non‐alcoholic fatty liver disease (NAFLD) based on bioengineered multicellular liver microtissues and a liver‐on‐a‐chip system. The microtissues consisting of four major liver cell types (primary human hepatocytes, stellate cells, Kupffe...

Despite considerable efforts in modeling liver disease in vitro, it remains difficult to recapitulate the pathogenesis of the advanced phases of non‐alcoholic fatty liver disease (NAFLD) with inflammation and fibrosis. Here, a liver‐on‐a‐chip platform with bioengineered multicellular liver microtissues is developed, composed of four major types of...

The development of theranostic platforms combining surface-enhanced Raman spectroscopy (SERS) imaging with NIR-stimulated photothermal therapy (PTT) is of utmost importance for the precise diagnosis and selective treatment of cancers, especially in superficial solid tumors. For this purpose, a versatile theranostic nanoprobe of liposomal layer-coat...

Wounds can take longer to heal in diabetic patients, increasing the risk of infections and other complications. The most common wounds in diabetic patients are diabetic foot ulcers, a severe complication associated with diabetes mellitus. The United States alone spends $18.7 billion annually on care for these wounds including pain and infection man...

Cancer immunotherapies, including immune checkpoint inhibitor (ICI)‐based therapies, have revolutionized cancer treatment. However, patient response to ICIs is highly variable, necessitating the development of methods to quickly assess efficacy. In this study, an array of miniaturized bioreactors has been developed to model tumor‐immune interaction...

Irregular hemodynamics affects the progression of various vascular diseases, such atherosclerosis or aneurysms. Despite the extensive hemodynamics studies on animal models, the inter-species differences between humans and animals hamper the translation of such findings. Recent advances in vascular tissue engineering and the suitability of in vitro...

Organic and inorganic nanoparticles (NPs) have shown promising outcomes in transdermal drug delivery. NPs can not only enhance the skin penetration of small/biomacromolecule therapeutic agents but can also impart control over drug release or target impaired tissue. Thanks to their unique optical, photothermal, and superparamagnetic features, NPs ha...

In article number 2003601, Shiming Zhang, Libo Zhao, Ali Khademhosseini, and co‐authors demonstrate a GelMA hydrogel biosensor capable of monitoring various human physiological signals. The device shows excellent stability. Robust chemical bonding and a reliable encapsulation approach are introduced to overcome detachment and water evaporation issu...

Fluorescent nanomaterials have been widely used in biological imaging due to their selectivity, sensitivity, and noninvasive nature. These characteristics make the materials suitable for real-time and in situ imaging. However, further development of highly biocompatible nanosystems with long-lasting fluorescent intensity and photostability is neede...

Microchannels in hydrogels play an essential role in enabling a smart contact lens. However, microchannels have rarely been created in commercial hydrogel contact lenses due to their sensitivity to conventional microfabrication techniques. Here, we report the fabrication of microchannels in poly(2-hydroxyethyl methacrylate) (poly(HEMA)) hydrogels t...

Animal models and traditional cell cultures are essential tools for drug development. However, these platforms can show striking discrepancies in efficacy and side effects when compared to human trials. These differences can lengthen the drug development process and even lead to drug withdrawal from the market. The establishment of preclinical drug...

Gelatin methacryloyl (GelMA) is a widely used hydrogel with skin‐derived gelatin acting as the main constituent. However, GelMA has not been used in the development of wearable biosensors, which are emerging devices that enable personalized healthcare monitoring. This work highlights the potential of GelMA for wearable biosensing applications by de...

The skin houses a developed vascular and lymphatic network with a significant population of immune cells. Because of the properties of the skin, nucleic acid delivery through the tissue has the potential to treat a range of pathologies, including genetic skin conditions, hyperproliferative diseases, cutaneous cancers, wounds, and infections. This w...

Thrombosis is a life‐threatening pathological condition in which blood clots form in blood vessels, obstructing or interfering with blood flow. Thrombolytic agents (TAs) are enzymes that can catalyze the conversion of plasminogen to plasmin to dissolve blood clots. The plasmin formed by TAs breaks down fibrin clots into soluble fibrin that finally...

In article number 1900456, Han‐Jun Kim, Ali Khademhosseini, and co‐workers analyzed the swelling, degradation, microstructural, mechanical, rheological and biological properties of various compositions of composite hydrogels consisting of gelatin and silicate nanoplatelets (SNPs). Understanding of mechanical and biological consequences of the chang...

In article number 1901794, Ali Khademhosseini, Nureddin Ashammakhi, and co‐workers, present a novel approach to develop oxygenated bioinks, using oxygen generating calcium peroxide particles. Cardiomyocyte‐laden oxygenated and 3D printed tissue constructs developed in this study can significantly support cell survival when applied in hypoxic condit...

Paclitaxel was encapsulated in chitosan nanoparticles using a microfluidic device and then was used as an anti‐cancer drug to treat skin cancer. The device resulted in a uniform fabrication of nanoparticles with tunable physicochemical properties. The anticancer efficiency of the drug was shown in vitro and in animal models. The results revealed th...

Separation of circulating tumor cells (CTCs) from blood samples and subsequent DNA extraction from these cells play a crucial role in cancer research and drug discovery. Microfluidics is a versatile technology that has been applied to create niche solutions to biomedical applications, such as cell separation and mixing, droplet generation, bioprint...

Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-in...

Oral administration is a pillar of the pharmaceutical industry and yet it remains challenging to administer hydrophilic therapeutics by the oral route. Smart and controlled oral drug delivery could bypass the physiological barriers that limit the oral delivery of these therapeutics. Micro- and nanoscale technologies, with an unprecedented ability t...

Brain tumors’ severity ranges from benign to highly aggressive and invasive. Bioengineering tools can assist in understanding the pathophysiology of these tumors from outside the body and facilitate development of suitable antitumoral treatments. Here, we first describe the physiology and cellular composition of brain tumors. Then, we discuss the d...

In article number 1909882, Samad Ahadian, Leonardo Morsut, Ali Khademhosseini, and co‐workers highlight the great potential of tissue engineering approaches and synthetic biology principles to fabricate biological tissues and cellular constructs in a biomimetic and precise manner via the manipulation of cell behavior and function. Advanced biomater...

Cell separation is a key step in many biomedical research areas including biotechnology, cancer research, regenerative medicine, and drug discovery. While conventional cell sorting approaches have led to high‐efficiency sorting by exploiting the cell's specific properties, microfluidics has shown great promise in cell separation by exploiting diffe...

In article number 2000086, KangJu Lee, Ali Khademhosseini, and co‐workers present a novel device for enhancing wound healing, the detachable hybrid microneedle depot. It is the first device to use a microneedle array to facilitate localized mesenchymal stem cell delivery with a minimal dose of cells.

Cell survival during the early stages of transplantation and before new blood vessels formation is a major challenge in translational applications of 3D bioprinted tissues. Supplementing oxygen (O2) to transplanted cells via an O2 generating source such as calcium peroxide (CPO) is an attractive approach to ensure cell viability. Calcium peroxide a...

In article number 2001837, Junmin Lee, Ali Khademhosseini, and co‐workers develop a bioreactor‐based platform to investigate the effect of human mesenchymal stem cell (hMSC) culture microenvironments including matrix rigidity and dynamic mechanical compression on their secretion level of pro‐angiogenic factors. It is demonstrated that these mechani...

Next generation engineered tissue constructs with complex and ordered architectures aim to better mimic the native tissue structures, largely due to advances in 3D bioprinting techniques. Extrusion bioprinting has drawn tremendous attention due to its widespread availability, cost‐effectiveness, simplicity, and its facile and rapid processing. Howe...

In the present study, the effectiveness of paclitaxel nanocrystals (PTX NCs) encapsulated in carboxymethyl chitosan (CMCS) nanoparticles (CMCS‐PTX NPs) as an anti‐cancer drug is evaluated. The CMCS nanoparticles are produced via a cross‐junction microfluidic device where PTX/CMCS concentration and flow rates in the device are optimized. The dynamic...

Transdermal delivery of water‐insoluble drugs via hydrogel‐based microneedle (MN) arrays is crucial for improving their therapeutic efficacies. However, direct loading of water‐insoluble drug into hydrophilic matrices remains challenging. Here, a biodegradable MN array patch that is fabricated from naturally derived polymer conjugates of gelatin me...

Stem cells secrete trophic factors that induce angiogenesis. These soluble factors are promising candidates for stem cell–based therapies, especially for cardiovascular diseases. Mechanical stimuli and biophysical factors presented in the stem cell microenvironment play important roles in guiding their behaviors. However, the complex interplay and...

Mesenchymal stem cells (MSCs) have been widely used for regenerative therapy. In most current clinical applications, MSCs are delivered by injection but face significant issues with cell viability and penetration into the target tissue due to a limited migration capacity. Some therapies have attempted to improve MSC stability by their encapsulation...

Biomaterials with suitable osteoimmunomodulation properties and ability to deliver osteoinductive biomolecules, such as bone morphogenetic proteins, are desired for bone regeneration. Herein, we report the development of mesoporous silica rods with large cone-shaped pores (MSR-CP) to load and deliver large protein drugs. It is noted that those cone...

In article number 1905910, Wujin Sun, Ali Khademhosseini, and co‐workers develop a transdermal microneedle patch from gelatin methacryloyl for minimally invasive extraction of interstitial fluid. Metabolites and drugs can be efficiently extracted for timely and accurate analysis, making the patch a potential platform to facilitate clinical diagnosi...

Objective Elastin gene deletion or mutation leads to arterial stenoses due to vascular smooth muscle cell (SMC) proliferation. Human induced pluripotent stem cells–derived SMCs can model the elastin insufficiency phenotype in vitro but show only partial rescue with rapamycin. Our objective was to identify drug candidates with superior efficacy in r...

Tissue engineering approaches, with the goals of replacing or recovering damaged or diseased tissues, or of reconstituting tissues in vitro for disease modeling and drug development, have the potential to make significant contributions to medicine. Advances in stem cell biology, biomaterial synthesis and characterization, and microscale technologie...

Injectable shear-thinning biomaterials (iSTBs) have great potential for in situ tissue regeneration through minimally invasive therapeutics. Previously, an iSTB was developed by combining gelatin with synthetic silicate nanoplatelets (SNPs) for the potential application to hemostasis and endovascular embolization. Hence, we synthesize iSTBs by vary...

The extraction of interstitial fluid (ISF) from skin using microneedles (MNs) has attracted growing interest in recent years due to its potential for minimally invasive diagnostics and biosensors. ISF collection by absorption into a hydrogel MN patch is a promising way that requires the materials to have outstanding swelling ability. Here, a gelati...

The detection of cardiac troponin I (cTnI) is clinically used to monitor myocardial infarctions (MI) and other heart diseases. The development of highly sensitive detection assays for cTnI is needed for the efficient diagnosis and monitoring of cTnI levels. Traditionally, enzyme-based immunoassays have been used for the detection of cTnI. However,...

Patterning of conducting polymer poly(3,4)ethylenedioxythiophene doped with polystyrene sulfonate (PEDOT:PSS) thin films directly on hydrophobic soft substrates is challenging. Shiming Zhang, Ali Khademhosseini, and co‐workers, in article number 1906016, report that hydrogels are capable of transfer‐printing patterned PEDOT:PSS thin films from glas...