Multi-Organ Microphysiological Systems Targeting Specific Organs for Recapitulating Disease Phenotypes via Organ Crosstalk.

Various systemic metabolic diseases arise from prolonged crosstalk across multiple organs, triggering serious impairments in various physiological systems. These diseases are intricate systemic pathologies characterized by complex mechanisms and an unclear etiology, making the treatment challenging. Efforts have been made to develop in vitro models to understand these diseases and devise new treatments.

Recent trends in embedded 3D bioprinting of vascularized tissue constructs.

3D bioprinting technology offers significant advantages in the fabrication of tissue and organ structures by allowing precise layer-by-layer patterning of cells and various biomaterials. However, conventional bioinks exhibit poor mechanical properties, which limit their use in the fabrication of large-scale vascularized tissue constructs. To address these limitations, recent studies have focused on the development of rapidly crosslinkable bioinks through chemical modification.

Stem Cells Within Three-Dimensional-Printed Scaffolds Facilitate Airway Mucosa and Bone Regeneration and Reconstruction of Maxillary Defects in Rabbits.

: Current craniofacial reconstruction surgical methods have limitations because they involve facial deformation. The craniofacial region includes many areas where the mucosa, exposed to air, is closely adjacent to bone, with the maxilla being a prominent example of this structure. Therefore, this study explored whether human neural-crest-derived stem cells (hNTSCs) aid bone and airway mucosal regeneration during craniofacial reconstruction using a rabbit model.

Engineering pore-enriched and pre-vascularized volumetric constructs for enhanced blood glucose regulation in type 1 diabetes therapy.

Managing type 1 diabetes mellitus (T1DM) presents significant challenges because of the complexity of replicating the microenvironment of pancreatic islets and ensuring the long-term viability and function of transplanted insulin-producing cells (IPCs). This study developed a functional approach that utilizes 3D bioprinting technology to create pore-enriched and pre-vascularized tissue constructs incorporating a pancreatic tissue-derived decellularized extracellular matrix and human-induced pluripotent stem cells (hiPSCs) aimed at enhancing blood glucose regulation in T1DM. We designed a volumetric 3D pancreatic tissue construct that supported the engraftment, survival, and insulin-producing functionality of hiPSC-derived IPCs.

3D engineering of diseased blood vessels for integrative-in silico mechanobiology study.

Vascular diseases are complex conditions orchestrated by multiple factors, including cellular components, biochemical stimuli, and mechanical forces. Despite the advancement of numerous therapeutic approaches, the global mortality associated with the diseases continues to escalate owing to a lack of understanding of the underlying pathologies. Tissue engineering and computational strategies have been recently developed to investigate diseased blood vessels from multifactorial perspective, enabling more accurate prediction of disease progression and opening new avenues for preclinical advances.

Bridge-rich and loop-less hydrogel networks through suppressed micellization of multiblock polyelectrolytes.

Most triblock copolymer-based physical hydrogels form three-dimensional networks through micellar packing, and formation of polymer loops represents a topological defect that diminishes hydrogel elasticity. This effect can be mitigated by maximizing the fraction of elastically effective bridges in the hydrogel network. Herein, we report hydrogels constructed by complexing oppositely charged multiblock copolymers designed with a sequence pattern that maximizes the entropic and enthalpic penalty of micellization.

Engineered Regenerative Isolated Peripheral Nerve Interface for Targeted Reinnervation.

A regenerative peripheral nerve interface (RPNI) offers a therapeutic solution for nerve injury through reconstruction of the target muscle. However, implanting a transected peripheral nerve into an autologous skeletal muscle graft in RPNI causes donor-site morbidity, highlighting the need for tissue-engineered skeletal muscle constructs. Here, an engineered regenerative isolated peripheral nerve interface (eRIPEN) is developed using 3D skeletal cell printing combined with direct electrospinning to create a nanofiber membrane envelop for host nerve implantation.

Degradation-controlled tissue extracellular sponge for rapid hemostasis and wound repair after kidney injury.

Patients diagnosed with T1a cancer undergo partial nephrectomy to remove the tumors. In the process of removing the tumors, loss of kidney volume is inevitable, and current surgical methods focus solely on hemostasis and wound closure. Here, we developed an implantable form of decellularized extracellular matrix sponge to target both hemostasis and wound healing at the lesion site.

Laminin-Augmented Decellularized Extracellular Matrix Ameliorating Neural Differentiation and Neuroinflammation in Human Mini-Brains.

Non-neural extracellular matrix (ECM) has limited application in humanized physiological neural modeling due to insufficient brain-specificity and safety concerns. Although brain-derived ECM contains enriched neural components, certain essential components are partially lost during the decellularization process, necessitating augmentation. Here, it is demonstrated that the laminin-augmented porcine brain-decellularized ECM (P-BdECM) is xenogeneic factor-depleted as well as favorable for the regulation of human neurons, astrocytes, and microglia.

3D bioprinted multilayered cerebrovascular conduits to study cancer extravasation mechanism related with vascular geometry.

Cerebral vessels are composed of highly complex structures that facilitate blood perfusion necessary for meeting the high energy demands of the brain. Their geometrical complexities alter the biophysical behavior of circulating tumor cells in the brain, thereby influencing brain metastasis. However, recapitulation of the native cerebrovascular microenvironment that shows continuities between vascular geometry and metastatic cancer development has not been accomplished.

3D biofabrication of diseased human skin models in vitro.

Human skin is an organ located in the outermost part of the body; thus, it frequently exhibits visible signs of physiological health. Ethical concerns and genetic differences in conventional animal studies have increased the need for alternative in vitro platforms that mimic the structural and functional hallmarks of natural skin. Despite significant advances in in vitro skin modeling over the past few decades, different reproducible biofabrication strategies are required to reproduce the pathological features of diseased human skin compared to those used for healthy-skin models.

3D Cell Printing of Advanced Vascularized Proximal Tubule-on-a-Chip for Drug Induced Nephrotoxicity Advancement.

Renal dysfunction due to drug-induced nephrotoxicity (DIN) affects >20% of the adult population worldwide. The vascularized proximal tubule is a complex structure that is often the primary site of drug-induced kidney injury. Herein, a vascularized proximal tubule-on-a-chip (Vas-POAC) was fabricated, demonstrating improved physiological emulation over earlier single-cell proximal tubule models.

Engineering of Uniform Epidermal Layers via Sacrificial Gelatin Bioink-Assisted 3D Extrusion Bioprinting of Skin.

To reconstruct an ideal full-thickness skin model, basal keratinocytes must be distributed as a confluent monolayer on the dermis. However, the currently available extrusion bioprinting method for the skin is limited when producing an air-exposed cellular monolayer because the cells are encapsulated within a bioink. This is the first study to use sacrificial gelatin-assisted extrusion bioprinting to reproduce a uniform and stratified epidermal layer.

The Correlation between Waist Circumference and the Pro-Inflammatory Adipokines in Diabetic Retinopathy of Type 2 Diabetes Patients.

Central obesity is one of the major risk factors for type 2 diabetes mellitus (DM), and the most common complication of DM is diabetic retinopathy. However, the exact relationship between obesity and DR remains unknown. In this study, we evaluate the effect of obesity on DR by comparing the aqueous humor-derived adipokines.

Coaxial cell printing of a human glomerular model: anglomerular filtration barrier and its pathophysiology.

Much effort has been expended in emulating the kidney's glomerular unit because of its limitless potential in the field of drug screening and nephrotoxicity testing in clinics. Herein, we fabricate a functional bilayer glomerular microvessel-on-a-chip that recapitulates the specific arrangement of the glomerular endothelial cell, podocyte layers, and the intervening glomerular basement membrane (GBM) in a single step. Our perfusable chip allows for the co-culture of monolayer glomerular endothelium and podocyte epithelium, which display mature functional markers of glomerular cells, and their proper interactions produce GBM proteins, which are the major components of the GBM.

Predicting multipotency of human adult stem cells derived from various donors through deep learning.

Adult stem cell-based therapeutic approaches have great potential in regenerative medicine because of their immunoregulatory properties and multidifferentiation capacity. Nevertheless, the outcomes of stem cell‑based therapies to date have shown inconsistent efficacy owing to donor variation, thwarting the expectation of clinical effects. However, such donor dependency has been elucidated by biological consequences that current research could not predict.

Extracellular matrix-based sticky sealants for scar-free corneal tissue reconstruction.

Regenerative medicine requires both tissue restoration and ease of compliance for clinical application. Considering this, sticky tissue sealants have been shown to have great potentials over surgical suturing and wound treatment. However, tissue sealants currently used pose challenges such as uncontrollable adhesion formation, mechanical mismatch, and lack of tissue restoration.

Feasibility and safety of a novel 3D-printed biodegradable biliary stent in an in vivo porcine model: a preliminary study.

To assess the feasibility and safety of a novel 3D-printed biodegradable biliary stent using polycaprolactone (PCL) in an in vivo porcine model. In this animal study using domestic pigs, biodegradable radiopaque biliary stents made of polycaprolactone (PCL) and barium sulfate were produced using 3D printing and surgically inserted into the common bile duct (CBD) of pigs (stent group, n = 12). Another five pigs were allocated to the control group that only underwent resection and anastomosis of the CBD without stent insertion.

Blood-Lymphatic Integrated System with Heterogeneous Melanoma Spheroids via In-Bath Three-Dimensional Bioprinting for Modelling of Combinational Targeted Therapy.

Although metastatic melanoma can be managed with chemotherapy, its heterogeneity and resistance to therapy remain poorly understood. In addition to the spread of melanoma in the bloodstream, melanoma-stroma interaction and the lymphatic system play active roles in said heterogeneity and resistance, leading to its progression and metastasis. Reproducing the complexities of the melanoma microenvironment in vitro will help understanding its progression and enhance the translatability of potential cancer therapeutics.

Enhancement strategy for effective vascular regeneration following myocardial infarction through a dual stem cell approach.

Since an impaired coronary blood supply following myocardial infarction (MI) negatively affects heart function, therapeutic neovascularization is considered one of the major therapeutic strategies for cell-based cardiac repair. Here, to more effectively achieve therapeutic neovascularization in ischemic hearts, we developed a dual stem cell approach for effective vascular regeneration by utilizing two distinct types of stem cells, CD31-endothelial cells derived from human induced pluripotent stem cells (hiPSC-ECs) and engineered human mesenchymal stem cells that continuously secrete stromal derived factor-1α (SDF-eMSCs), to simultaneously promote natal vasculogenesis and angiogenesis, two core mechanisms of neovascularization. To induce more comprehensive vascular regeneration, we intramyocardially injected hiPSC-ECs to produce de novo vessels, possibly via vasculogenesis, and a 3D cardiac patch encapsulating SDF-eMSCs (SDF-eMSC-PA) to enhance angiogenesis through prolonged secretion of paracrine factors, including SDF-1α, was implanted into the epicardium of ischemic hearts.

Biomaterial-based 3D bioprinting strategy for orthopedic tissue engineering.

The advent of three-dimensional (3D) bioprinting has enabled impressive progress in the development of 3D cellular constructs to mimic the structural and functional characteristics of natural tissues. Bioprinting has considerable translational potential in tissue engineering and regenerative medicine. This review highlights the rational design and biofabrication strategies of diverse 3D bioprinted tissue constructs for orthopedic tissue engineering applications.

A Bioprinted Bruch's Membrane for Modeling Smoke-Induced Retinal Pigment Epithelium Degeneration via Hybrid Membrane Printing Technology.

The retinal pigment epithelium (RPE) not only forms the outer blood-retinal barrier (oBRB) but also plays a multifunctional role in the ocular system. The loss of this epithelium leads to serious diseases resulting in vision impairment. No effective treatment is available for the repair of RPE damage.

3D cell-printing of gradient multi-tissue interfaces for rotator cuff regeneration.

Owing to the prevalence of rotator cuff (RC) injuries and suboptimal healing outcome, rapid and functional regeneration of the tendon-bone interface (TBI) after RC repair continues to be a major clinical challenge. Given the essential role of the RC in shoulder movement, the engineering of biomimetic multi-tissue constructs presents an opportunity for complex TBI reconstruction after RC repair. Here, we propose a gradient cell-laden multi-tissue construct combined with compositional gradient TBI-specific bioinks via 3D cell-printing technology.

Three-Dimensional Microfilament Printing of a Decellularized Extracellular Matrix (dECM) Bioink Using a Microgel Printing Bath for Nerve Graft Fabrication and the Effectiveness of dECM Graft Combined with a Polycaprolactone Conduit.

Various synthetic and decellularized materials are being used to reconstruct peripheral nerve defects and replace autologous nerve grafts. In this study, we developed a microgel printing bath to three-dimensionally (3D) print a peripheral nervous system decellularized extracellular matrix nerve graft reinforced by a polycaprolactone (PCL) conduit. The straightforward fabrication method of an alginate microgel-supplemented printing bath allows a 30 μm filament resolution of a low viscous decellularized extracellular matrix hydrogel with neutral pH.