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Messenger RNA (mRNA) therapy is the intracellular delivery of mRNA to produce desired therapeutic proteins. Developing strategies for local mRNA delivery is still required where direct intra‐articular injections are inappropriate for targeting a specific tissue. The mRNA delivery efficiency depends on protecting nucleic acids against nuclease‐mediated degradation and safe site‐specific intracellular delivery. Herein, novel mRNA‐releasing matrices based on RGD‐moiety‐rich gelatin methacryloyl (GelMA) microporous annealed particle (MAP) scaffolds are reported. GelMA concentration in aerogel‐based microgels (µgels) produced through a microfluidic process, MAP stiffnesses, and microporosity are crucial parameters for cell adhesion, spreading, and proliferation. After being loaded with mRNA complexes, MAP scaffolds composed of 10% GelMA µgels display excellent cell viability with increasing cell infiltration, adhesion, proliferation, and gene transfer. The intracellular delivery is achieved by the sustained release of mRNA complexes from MAP scaffolds and cell adhesion on mRNA‐releasing scaffolds. These findings highlight that hybrid systems can achieve efficient protein expression by delivering mRNA complexes, making them promising mRNA‐releasing biomaterials for tissue engineering. [ABSTRACT FROM AUTHOR]

Flexible bioelectronic devices have attracted immense interest in the biomedical field because of their wearability, biocompatibility, diverse functionalities, and ease of personalization. Recently, flexible energy harvesters have been developed, and attempts have been made to integrate them with such devices, enabling them to operate without external batteries or power supply. In this review, the latest advances in flexible energy harvesters and their use in wearable devices are discussed. Energy harvesters for versatile biomedical applications are summarized. Finally, the challenges and future perspectives of self‐powered biomedical systems that enable wearable healthcare monitoring and management are outlined. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a malignant and deadly form of liver cancer with limited treatment options. Transcatheter arterial chemoembolization, a procedure that delivers embolic and chemotherapeutic agents through blood vessels, is a promising cancer treatment strategy. However, it still faces limitations, such as inefficient agent delivery and the inability to address tumor‐induced immunosuppression. Here, a drug‐eluting shear‐thinning hydrogel (DESTH) loaded with chemotherapeutic and immunotherapeutic agents in nanocomposite hydrogels composed of gelatin and nanoclays is presented as a therapeutic strategy for a catheter‐based endovascular anticancer approach. DESTH is manually deliverable using a conventional needle and catheter. In addition, drug release studies show a sustained and pH‐dependent co‐delivery of the chemotherapy doxorubicin (acidic pH) and the immune‐checkpoint inhibitor aPD‐1 (neutral pH). In a mouse liver tumor model, the DESTH‐based chemo/immunotherapy combination has the highest survival rate and smallest residual tumor size. Finally, immunofluorescence analysis confirms that DESTH application enhances cell death and increases intratumoral infiltration of cytotoxic T‐cells. In conclusion, the results show that DESTH, which enables efficient ischemic tumor cell death and effective co‐delivery of chemo‐ and immunotherapeutic agents, may have the potential to be an effective therapeutic modality in the treatment of HCC. [ABSTRACT FROM AUTHOR]

Sac embolization of abdominal aortic aneurysms (AAAs) remains clinically limited by endoleak recurrences. These recurrences are correlated with recanalization due to the presence of endothelial lining and matrix metalloproteinases (MMPs)‐mediated aneurysm progression. This study incorporates doxycycline (DOX), a well‐known sclerosant and MMPs inhibitor, into a shear‐thinning biomaterial (STB)‐based vascular embolizing hydrogel. The addition of DOX is expected to improve embolizing efficacy while preventing endoleaks by inhibiting MMP activity and promoting endothelial removal. The results show that STBs containing 4.5% w/w silicate nanoplatelet and 0.3% w/v of DOX are injectable and have a twofold increase in storage modulus compared to those without DOX. STB‐DOX hydrogels also reduced clotting time by 33% compared to untreated blood. The burst release of DOX from the hydrogels show sclerosing effects after 6 h in an ex vivo pig aorta model. Sustained release of DOX from hydrogels on endothelial cells shows MMP inhibition (approximately an order of magnitude larger than control groups) after 7 days. The hydrogels successfully occlude a patient‐derived abdominal aneurysm model at physiological blood pressures and flow rates. The sclerosing and MMP inhibition characteristics in the engineered multifunctional STB‐DOX hydrogels may provide promising opportunities for the efficient embolization of aneurysms in blood vessels. [ABSTRACT FROM AUTHOR]

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 exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol‐gel, aging, drying, and self‐assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic‐based technologies and 3D printing can be combined with aerogel‐based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel‐based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels. [ABSTRACT FROM AUTHOR]

Developing theranostic devices to detect bleeding and effectively control hemorrhage in the prehospital setting is an unmet medical need. Herein, an all‐in‐one theranostic platform is presented, which is constructed by sandwiching silk fibroin (SF) between two silver nanowire (AgNW) based conductive electrodes to non‐enzymatically diagnose local bleeding and stop the hemorrhage at the wound site. Taking advantage of the hemostatic property of natural SF, the device is composed of a shape‐memory SF sponge, facilitating blood clotting, with ≈82% reduction in hemostatic time in vitro as compared with untreated blood. Furthermore, this sandwiched platform serves as a capacitive sensor that can detect bleeding and differentiate between blood and other body fluids (i.e., serum and water) via capacitance change. In addition, the AgNW electrode endows anti‐infection efficiency against Escherichia coli and Staphylococcus aureus. Also, the device shows excellent biocompatibility and gradually biodegrades in vivo with no major local or systemic inflammatory responses. More importantly, the theranostic platform presents considerable hemostatic efficacy comparable with a commercial hemostat, Dengen, in rat liver bleeding models. The theranostic platform provides an unexplored strategy for the intelligent management of hemorrhage, with the potential to significantly improve patients' well‐being through the integration of diagnostic and therapeutic capabilities. [ABSTRACT FROM AUTHOR]

Ionic liquids (ILs) exhibit unique properties of good ionic conductivity, electrochemical and thermal stability, and nonflammability, which make them promising candidates for biomedical applications. The limitations of their cytocompatibility are enhanced by using bioionic liquids (BILs) derived from biological molecules such as amines, sugars, and organic acids. BILs can be synthesized using tailorable chemistries that enable their immobilization onto biopolymers. For example, the cholinium ion and its derivatives have found significant interest in tissue engineering and drug delivery systems. Ion‐doped BIL‐functionalized polymers and their composites can also be used to design pH and electrical responsive actuators and sensors. The cytocompatibility and low immunogenicity of BIL‐functionalized polymers enable the possibilities of their use for power storage devices as well as implantable devices. These devices are gaining recognition and importance in nucleic acid delivery and molecular medicine. This review focuses on the recent advances of BILs in biomedical applications. Specifically, the review explores BILs as agents for biopolymer functionalization and highlights BILs as solvents for supermolecular ionic networks. [ABSTRACT FROM AUTHOR]

Adhesive materials have recently drawn intensive attention due to their excellent sealing ability, stimulating advances in materials science and industrial usage. However, reported adhesives usually exhibit weak adhesion strength, require high pressure for strong bonding, and display severe adhesion deterioration in various harsh environments. In this study, instead of water or organic solvents, a deep eutectic solvent (DES) is used as the medium for the photopolymerization of zwitterionic and polarized monomers, thus generating a novel ionogel with tunable mechanical properties. Multiple hydrogen bonds and electrostatic interactions between DES and monomers facilitated ultrafast gelation and instant bonding without any external pressure, which has rarely been reported previously. Furthermore, high adhesion in different harsh environments (e.g., water, acidic and basic buffers, and saline solutions) and onto hydrophilic (e.g., glass and tissues) and hydrophobic (e.g., polymethyl methacrylate, polystyrene, and polypropylene) adherends is demonstrated. Also, the high stretchability of the ionogel at extreme temperatures (−80 and 80 °C) indicates its widespread applications. Furthermore, the biocompatible ionogel shows high burst pressure onto stomach and intestine tissues to prevent liquid leakage, highlighting its potential as an adhesive patch. This ionogel provides unprecedented opportunities in the packaging industry, marine engineering, medical adhesives, and electronic assembly. [ABSTRACT FROM AUTHOR]

In natural microenvironment, various proteins containing adhesive ligands in fibrous and non‐fibrous structures dynamically couple and decouple to regulate stem cell fate. Herein, materials presenting movably couplable ligands are developed by grafting liganded gold nanoparticles (AuNPs) to a substrate followed by flexibly grafting liganded movable linear nanomaterials (MLNs) to the substrate via a long bendable linker, thereby creating a space between the MLNs and the AuNPs in the decoupled state. Magnetic control of the MLNs decreases this space via the bending of the linker to couple the MLNs to the AuNPs. Remote control of ligand coupling stimulates integrin recruitment to the coupled ligands, thereby non‐toxically facilitating the focal adhesion, mechanosensing, and potential differentiation of stem cells, which is suppressed by ligand decoupling. Versatile tuning of size, aspect ratio, distributions, and ligands of the MLNs can help to decipher dynamic ligand‐coupling‐dependent stem cell fate to advance regenerative therapies. [ABSTRACT FROM AUTHOR]

Fast healing of diabetic wounds remains a major clinical challenge. Herein, this study reports a strategy to combine nanofiber aerogels containing precision macrochannels and the LL‐37‐mimic peptide W379 for rapid diabetic wound healing. Nanofiber aerogels consisting of poly(glycolide‐co‐lactide) (PGLA 90:10)/gelatin and poly‐p‐dioxanone (PDO)/gelatin short electrospun fiber segments are prepared by partially anisotropic freeze‐drying, cross‐linking, and sacrificial templating with 3D printed meshes, exhibiting nanofibrous architecture and precision micro‐/macrochannels. Like human cathelicidin LL‐37, W379 peptide at a concentration of 3 µg mL−1 enhances the migration and proliferation of keratinocytes and dermal fibroblasts in a cell scratch assay and a proliferation assay. In vivo studies show that nanofiber aerogels with precision macrochannels can greatly promote cell penetration compared to aerogels without macrochannels. Relative to control and aerogels with and without macrochannels, adding W379 peptides to aerogels with precision macrochannels shows the best efficacy in healing diabetic wounds in mice in terms of cell infiltration, neovascularization, and re‐epithelialization. The fast re‐epithelization could be due to the upregulation of phospho‐extracellular signal‐regulated kinase (p38 mitogen‐activated protein kinase) after treatment with W379. Together, the approach developed in this study could be promising for the treatment of diabetic wounds and other chronic wounds. [ABSTRACT FROM AUTHOR]

Exosomes, a form of small extracellular vesicles, play a crucial role in the metastasis of cancers and thus are investigated as potential biomarkers for cancer diagnosis. However, conventional detection methods like immune‐based assay and microRNA analyses are expensive and require tedious pretreatments and lengthy analysis time. Since exosomes related to cancers are reported to exist in tears, a poly(2‐hydroxyethyl methacrylate) contact lens embedded with antibody‐conjugated signaling microchambers (ACSM‐PCL) capable of detecting tear exosomes is reported. The ACSM‐PCL exhibits high optical transparency and mechanical properties, along with extraordinary biocompatibility and good sensitivity to exosomes. A gold nanoparticle colorimetric assay is employed to visualize captured exosomes. The ACSM‐PCL can detect exosomes in the pH range of 6.5–7.4 (similar to the human tear pH) and have a strong recovery yield in bovine serum albumin solutions. In particular, the ACSM‐PCL can detect exosomes in various solutions, including regular buffer, cell culture media from various cell lines, and human tears. Finally, the ACSM‐PCL can differentiate expression of exosome surface proteins hypothesized as cancer biomarkers. With these encouraging results, this ACSM‐PCL is promised to be the next generation smart contact lens as an easy‐to‐use, rapid, noninvasive monitoring platform of cancer pre‐screening and supportive diagnosis. [ABSTRACT FROM AUTHOR]

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 manner. Although this technology is still in its infancy and far from being translated into the clinic, preclinical trials have shown some promise for the broad applications of multifunctional MN devices. The main challenge facing the fabrication of smart MN patches is the integration of multiple modules, such as drug carriers, highly sensitive biosensors, and data analyzers in one miniaturized MN device. Researchers have shown the feasibility of creating smart MNs by integrating stimuli‐responsive biomaterials and advanced microscale technologies, such as microsensors and microfluidic systems, to precisely control the transportation of biofluids and drugs throughout the system. These multifunctional MN devices can be envisioned in two distinct strategies. The first type includes individual drug delivery and biosensing MN units with a microfluidic system and a digital analyzer responsible for fluid transportation and communication between these two modules. The second type relies on smart biomaterials that can function as drug deliverers and biosensors by releasing drugs in a stimuli‐responsive manner. These smart biomaterials can undergo structural changes when exposed to external stimuli, such as pH and ionic changes, mimicking the biological systems. Studies have demonstrated a high potential of hydrogel‐based MN devices for a wide variety of biomedical applications, such as drug and cell delivery, as well as interstitial fluid extraction. Biodegradable hydrogels have also been advantageous for fabricating multifunctional MNs due to their high loading capacity and biocompatibility with the drug of choice. Here, we first review a set of MN devices that can be employed either for biosensing or delivery of multiple target molecules and compare them to the conventional and more simple systems, which are mainly designed for single‐molecule sensing or delivery. Subsequently, we expand our insight into advanced MN systems with multiple competencies, such as body fluid extraction, biosensing, and drug delivery at the point of care. The improvement of biomaterials knowledge and biofabrication techniques will allow us to efficiently tune the next generation of smart MNs and provide a realistic platform for more effective personalized therapeutics. [ABSTRACT FROM AUTHOR]

It is known that changes in the mechanical properties of tissues are associated with the onset and progression of certain diseases. Ultrasound elastography is a technique to characterize tissue stiffness using ultrasound imaging either by measuring tissue strain using quasi‐static elastography or natural organ pulsation elastography, or by tracing a propagated shear wave induced by a source or a natural vibration using dynamic elastography. In recent years, deep learning has begun to emerge in ultrasound elastography research. In this review, several common deep learning frameworks in the computer vision community, such as multilayered perceptron, convolutional neural network, and recurrent neural network, are described. Then, recent advances in ultrasound elastography using such deep learning techniques are revisited in terms of algorithm development and clinical diagnosis. Finally, the current challenges and future developments of deep learning in ultrasound elastography are prospected. [ABSTRACT FROM AUTHOR]

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, materials, and sensing modalities have been reported to address this need. However, a trade‐off arises between device performance and device complexity. Inspired by the microstructure of the spinosum at the dermo epidermal junction in skin, a low‐cost, scalable, and high‐performance piezoresistive sensor is developed with high sensitivity (0.144 kPa‐1), extensive sensing range (0.1–15 kPa), fast response time (less than 150 ms), and excellent long‐term stability (over 1000 cycles). Furthermore, the piezoresistive functionality of the device is realized via a flexible transparent electrode (FTE) using a highly stable reduced graphene oxide self‐wrapped copper nanowire network. The developed nanowire‐based spinosum microstructured FTEs are amenable to wearable electronics applications. [ABSTRACT FROM AUTHOR]

The integration of robotic systems into bioprinters can facilitate the construction of high-resolution and complex tissue structures via digitally controlled robotic arms equipped with different types of printheads.17 Each of the printing components can be individually employed to fabricate different parts of tissue constructs, which can subsequently be assembled to create multi-functional heterogeneous structures. Three-dimensional (3D) bioprinting is an emerging additive manufacturing technique that has shown potential for fabricating complex biologically active constructs by exerting control over the positioning of cells and biomaterials using computer-aided systems. Harvesting cells from their native environments and manipulating them using bioprinters can expose cells to high levels of stress and change their gene-expression profiles.1 In addition, some cells may die or migrate out of the bioprinted constructs after implantation. Also, the inclusion of stimuli-responsive and AI components in bioinks can control the in vivo functionality of bioprinted tissues after implantation and pave the way toward constructing biomimetic and functional tissue constructs. [Extracted from the article]

Minimally invasive treatment via injectable delivery of cells has drawn extensive attention for tissue regeneration because it reduces the need for substantial open surgery and fits tissue defects with complex shapes, making it a suitable option for repairing articular cartilage defects. This work presents an alkaline treatment method to fabricate open‐porous poly (lactic‐co‐glycolic acid) microspheres (OPMs) as bone marrow stromal cells (BMSCs) carriers for cartilage regeneration. OPMs have better biodegradation property and the extended pores can provide easier access for cells to the internal space. The BMSCs cultured with OPMs can display enhanced cell proliferation, up‐regulated expression of cartilage‐related mRNAs and proteins, and improved cartilage regeneration in vitro and in vivo. These results highlight the advantage and potential of using OPMs fabricated via simple alkaline treatment as injectable stem cell carriers for cartilage regeneration through minimally invasive procedures. [ABSTRACT FROM AUTHOR]

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 fabrication of smart contact lenses for biomedical applications, including contact lens materials, fabrication technologies, and integration, are presented. Furthermore, biosensors implemented in contact lenses to measure lactic acid, glucose, intraocular pressure, and other key metabolites in tears are highlighted. Applications of smart contact lenses in drug delivery are also described. These unique features make smart contact lenses promising diagnostic and treatment devices. Challenges and future opportunities for further applications of smart contact lenses in biomedicine are also discussed. [ABSTRACT FROM AUTHOR]

Two‐dimensional (2D) metal organic frameworks (MOFs), are an emerging class of layered nanomaterials with well‐defined structure and modular composition. The unique pore structure, high flexibility, tunability, and ability to introduce desired functionality within the structural framework, have led to potential use of MOFs in biomedical applications. This article critically reviews the application of 2D MOFs for therapeutic delivery, tissue engineering, bioimaging, and biosensing. Further, discussion on the challenges and strategies in next generation of 2D MOFs are also included. This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in Biology [ABSTRACT FROM AUTHOR]

Endovascular embolization to treat vascular hemorrhage involves pushing coil‐shaped metal wires into the artery repeatedly until they are densely packed to slow the blood flow and clot. However, coil embolization is associated with high rebleeding rates, unpredictable economics and, most importantly, they rely on the patient's ability to make a clot. These issues are exacerbated when the patient is anticoagulated or coagulopathic. A novel bioengineered tantalum‐loaded nanocomposite hydrogel for gel embolic material (Ta‐GEM) that can be rapidly delivered using clinical catheters for instant hemostasis regardless of the coagulopathic state is reported. Ta‐GEM formulation is visible by most of the clinically available imaging modalities including ultrasound, computed tomography, magnetic resonance imaging, and fluoroscopy without significant artifact. In addition, Ta‐GEM can be retrieved, allowing temporary vascular occlusion, and it can be used to rescue cases of failed coil embolization. Ta‐GEM occlusion of first‐order arteries such as the renal artery and iliac artery in a swine model is found to be safe and durable; by 28 days, 75% of the injected Ta‐GEM in the arterial lumen is replaced by dense connective tissue. Altogether, this study demonstrates that Ta‐GEM has many advantages over the current technologies and has potential applications in clinical practice. [ABSTRACT FROM AUTHOR]

Strong, stretchable, and durable biomaterials with shape memory properties can be useful in different biomedical devices, tissue engineering, and soft robotics. However, it is challenging to combine these features. Semi‐crystalline polyvinyl alcohol (PVA) has been used to make hydrogels by conventional methods such as freeze–thaw and chemical crosslinking, but it is formidable to produce strong materials with adjustable properties. Herein, a method to induce crystallinity and produce physically crosslinked PVA hydrogels via applying high‐concentration sodium hydroxide into dense PVA polymer is introduced. Such a strategy enables the production of physically crosslinked PVA biomaterial with high mechanical properties, low water content, resistance to injury, and shape memory properties. It is also found that the developed PVA hydrogel can recover 90% of plastic deformation due to extension upon supplying water, providing a strong contraction force sufficiently to lift objects 1100 times more than their weight. Cytocompatibility, antifouling property, hemocompatibility, and biocompatibility are also demonstrated in vitro and in vivo. The fabrication methods of PVA‐based catheters, injectable electronics, and microfluidic devices are demonstrated. This gelation approach enables both layer‐by‐layer and 3D printing fabrications. [ABSTRACT FROM AUTHOR]

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 screening platforms that have higher relevancy to physiological conditions is desirable to facilitate drug development. Here, a heart‐on‐a‐chip platform, incorporating microgrooves and electrical pulse stimulations to recapitulate the well‐aligned structure and synchronous beating of cardiomyocytes (CMs) for drug screening, is reported. Each chip is made with facile lithographic and laser‐cutting processes that can be easily scaled up to high‐throughput format. The maturation and phenotypic changes of CMs cultured on the heart‐on‐a‐chip is validated and it can be treated with various drugs to evaluate cardiotoxicity and cardioprotective efficacy. The heart‐on‐a‐chip can provide a high‐throughput drug screening platform in preclinical drug development. [ABSTRACT FROM AUTHOR]

Immunotherapy is a class of promising anticancer treatments that has recently gained attention due to surging numbers of FDA approvals and extensive preclinical studies demonstrating efficacy. Nevertheless, further clinical implementation has been limited by high variability in patient response to different immunotherapeutic agents. These treatments currently do not have reliable predictors of efficacy and may lead to side effects. The future development of additional immunotherapy options and the prediction of patient‐specific response to treatment require advanced screening platforms associated with accurate and rapid data interpretation. Advanced engineering approaches ranging from sequencing and gene editing, to tumor organoids engineering, bioprinted tissues, and organs‐on‐a‐chip systems facilitate the screening of cancer immunotherapies by recreating the intrinsic and extrinsic features of a tumor and its microenvironment. High‐throughput platform development and progress in artificial intelligence can also improve the efficiency and accuracy of screening methods. Here, these engineering approaches in screening cancer immunotherapies are highlighted, and a discussion of the future perspectives and challenges associated with these emerging fields to further advance the clinical use of state‐of‐the‐art cancer immunotherapies are provided. [ABSTRACT FROM AUTHOR]

Converting biopolymers to extracellular matrix (ECM)‐mimetic hydrogel‐based scaffolds has provided invaluable opportunities to design in vitro models of tissues/diseases and develop regenerative therapies for damaged tissues. Among biopolymers, gelatin and its crosslinkable derivatives, such as gelatin methacryloyl (GelMA), have gained significant importance for biomedical applications due to their ECM‐mimetic properties. Recently, we have developed the first class of in situ forming GelMA microporous hydrogels based on the chemical annealing of physically crosslinked GelMA microscale beads (microgels), which addressed several key shortcomings of bulk (nanoporous) GelMA scaffolds, including lack of interconnected micron‐sized pores to support on‐demand three‐dimensional‐cell seeding and cell–cell interactions. Here, we address one of the limitations of in situ forming microporous GelMA hydrogels, that is, the thermal instability (melting) of their physically crosslinked building blocks at physiological temperature, resulting in compromised microporosity. To overcome this challenge, we developed a two‐step fabrication strategy in which thermostable GelMA microbeads were produced via semi‐photocrosslinking, followed by photo‐annealing to form stable microporous scaffolds. We show that the semi‐photocrosslinking step (exposure time up to 90 s at an intensity of ~100 mW/cm2 and a wavelength of ~365 nm) increases the thermostability of GelMA microgels while decreasing their scaffold forming (annealing) capability. Hinging on the tradeoff between microgel and scaffold stabilities, we identify the optimal crosslinking condition (exposure time ~60 s) that enables the formation of stable annealed microgel scaffolds. This work is a step forward in engineering in situ forming microporous hydrogels made up from thermostable GelMA microgels for in vitro and in vivo applications at physiological temperature well above the gelatin melting point. [ABSTRACT FROM AUTHOR]

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. However, poor printing resolution and low speed have limited its fidelity and clinical implementation. To circumvent the downsides associated with extrusion printing, microfluidic technologies are increasingly being implemented in 3D bioprinting for engineering living constructs. These technologies enable biofabrication of heterogeneous biomimetic structures made of different types of cells, biomaterials, and biomolecules. Microfluiding bioprinting technology enables highly controlled fabrication of 3D constructs in high resolutions and it has been shown to be useful for building tubular structures and vascularized constructs, which may promote the survival and integration of implanted engineered tissues. Although this field is currently in its early development and the number of bioprinted implants is limited, it is envisioned that it will have a major impact on the production of customized clinical‐grade tissue constructs. Further studies are, however, needed to fully demonstrate the effectiveness of the technology in the lab and its translation to the clinic. [ABSTRACT FROM AUTHOR]