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Abstract Objective Build a microlaryngoscopy surgical simulator for endoscopic laryngeal surgery using standard microsurgical instruments and a CO2 laser. Study design Anatomical modeling, CAD design and 3D printed manufacturing. Subjects and methods We created a modular design for a microlaryngoscopy simulator in CAD software. Components include plastic and stainless‐steel models of a standard operating laryngoscope and a cassette system for mounting porcine or synthetic models of the vocal folds. All simulator parts, including the metallic laryngoscope model, were manufactured using 3D printing technology. Tumors were simulated in porcine tissue models by injecting a soy protein‐based tumor phantom. Residents and faculty in the Louisiana State University otolaryngology department evaluated the system. Each participant performed microlaryngoscopy with laser resection on a porcine larynx and cold instrument procedures on synthetic vocal folds. Participants scored the simulator using a 5‐point Likert scale. Results The microlaryngeal surgical simulator demonstrated in this project is realistic, economical, and easily assembled. We have included 3D printed parts files and detailed assembly instructions that will enable educators interested in surgical simulation to build the device. Participants in the simulator evaluation session felt that the simulator faithfully represented the procedure to resect vocal fold lesions using a CO2 laser. The synthetic model allows the trainee to develop hand‐eye coordination while using standard laryngeal instruments. Conclusions The simulator described herein will enable surgeons to acquire the surgical skills necessary to perform operative microlaryngoscopy prior to operating on live patients.

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition and wound healing include lack of bacterial contamination, good tissue perfusion, and reduced mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments. In this review, we discuss bioengineering advances in 1) non-invasive detection of biologic and physiologic factors of the healing wound, 2) visualizing and modeling the ECM, and 3) computational tools that efficiently evaluate the complex data acquired from the wounds based on basic science, preclinical, translational and clinical studies, that would allow us to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation of the tissues. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the wound matrix, linearity of collagen, and live tracking of components within the wound microenvironment. Computational modeling of the wound matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed.

Abstract Polymeric nanoparticles have been investigated as potential delivery systems for therapeutic compounds to address many ailments including eye disease. The stability and spatiotemporal distribution of polymeric nanoparticles in the eye are important regarding the practical applicability and efficacy of the delivery system in treating eye disease. We selected poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with lutein, a carotenoid antioxidant associated with eye health, as our model ophthalmic nanodelivery system and evaluated its stability when suspended in various conditions involving temperature and light exposure. We also assessed the ocular biodistribution of the fluorescently labeled nanoparticle vehicle when administered topically. Lutein-loaded nanoparticles were stable in suspension when stored at 4 °C with only 26% lutein release and no significant lutein decay or changes in nanoparticle morphology. When stored at 25 °C and 37 °C, these NPs showed signs of bulk degradation, had significant lutein decay compared to 4 °C, and released over 40% lutein after 5 weeks in suspension. Lutein-loaded nanoparticles were also more resistant to photodegradation compared to free lutein when exposed to ultraviolet (UV) light, decaying approximately 5 times slower. When applied topically in vivo, Cy5-labled nanoparticles showed high uptake in exterior eye tissues including the cornea, episcleral tissue, and sclera. The choroid was the only inner eye tissue that was significantly higher than the control group. Decreased fluorescence in all exterior eye tissues and the choroid at 1 h compared to 30 min indicated rapid elimination of nanoparticles from the eye.

Abstract Advantages of polymeric nanoparticles as drug delivery systems include controlled release, enhanced drug stability and bioavailability, and specific tissue targeting. Nanoparticle properties such as hydrophobicity, size, and charge, mucoadhesion, and surface ligands, as well as administration route and suspension media affect their ability to overcome ocular barriers and distribute in the eye, and must be carefully designed for specific target tissues and ocular diseases. This review seeks to discuss the available literature on the biodistribution of polymeric nanoparticles and discuss the effects of nanoparticle composition and administration method on their ocular penetration, distribution, elimination, toxicity, and efficacy, with potential impact on clinical applications.

Abstract Nerve guidance conduits (NGCs) have emerged from recent advances within tissue engineering as a promising alternative to autografts for peripheral nerve repair. NGCs are tubular structures with engineered biomaterials, which guide axonal regeneration from the injured proximal nerve to the distal stump. NGC design can synergistically combine multiple properties to enhance proliferation of stem and neuronal cells, improve nerve migration, attenuate inflammation and reduce scar tissue formation. The aim of most laboratories fabricating NGCs is the development of an automated process that incorporates patient-specific features and complex tissue blueprints (e.g. neurovascular conduit) that serve as the basis for more complicated muscular and skin grafts. One of the major limitations for tissue engineering is lack of guidance for generating tissue blueprints and the absence of streamlined manufacturing processes. With the rapid expansion of machine intelligence, high dimensional image analysis, and computational scaffold design, optimized tissue templates for 3D bioprinting (3DBP) are feasible. In this review, we examine the translational challenges to peripheral nerve regeneration and where machine intelligence can innovate bottlenecks in neural tissue engineering.

Engineering microenvironments for accelerated myocardial repair is a challenging goal. Cell therapy has evolved over a few decades to engraft therapeutic cells to replenish lost cardiomyocytes in the left ventricle. However, compelling evidence supports that tailoring specific signals to endogenous cells rather than the direct integration of therapeutic cells could be an attractive strategy for better clinical outcomes. Of many possible routes to instruct endogenous cells, we reviewed recent cases that extracellular matrix (ECM) proteins contribute to enhanced cardiomyocyte proliferation from neonates to adults. In addition, the presence of ECM proteins exerts biophysical regulation in tissue, leading to the control of microenvironments and adaptation for enhanced cardiomyocyte proliferation. Finally, we also summarized recent clinical trials exclusively using ECM proteins, further supporting the notion that engineering ECM proteins would be a critical strategy to enhance myocardial repair without taking any risks or complications of applying therapeutic cardiac cells.

Regenerating lost or damaged tissue is the primary goal of Tissue Engineering. 3D bioprinting technologies have been widely applied in many research areas of tissue regeneration and disease modeling with unprecedented spatial resolution and tissue-like complexity. However, the extraction of tissue architecture and the generation of high-resolution blueprints are challenging tasks for tissue regeneration. Traditionally, such spatial information is obtained from a collection of microscopic images and then combined together to visualize regions of interest. To fabricate such engineered tissues, rendered microscopic images are transformed to code to inform a 3D bioprinting process. If this process is augmented with data-driven approaches and streamlined with machine intelligence, identification of an optimal blueprint can become an achievable task for functional tissue regeneration. In this review, our perspective is guided by an emerging paradigm to generate a blueprint for regeneration with machine intelligence. First, we reviewed recent articles with respect to our perspective for machine intelligence-driven information retrieval and fabrication. After briefly introducing recent trends in information retrieval methods from publicly available data, our discussion is focused on recent works that use machine intelligence to discover tissue architectures from imaging and spectral data. Then, our focus is on utilizing optimization approaches to increase print fidelity and enhance biomimicry with machine learning (ML) strategies to acquire a blueprint ready for 3D bioprinting.

The extracellular matrix (ECM) is a critical cue to direct tumorigenesis and metastasis. Although two-dimensional (2D) culture models have been widely employed to understand breast cancer microenvironments over the past several decades, the 2D models still exhibit limited success. Overwhelming evidence supports that three dimensional (3D), physiologically relevant culture models are required to better understand cancer progression and develop more effective treatment. Such platforms should include cancer-specific architectures, relevant physicochemical signals, stromal–cancer cell interactions, immune components, vascular components, and cell-ECM interactions found in patient tumors. This review briefly summarizes how cancer microenvironments (stromal component, cell-ECM interactions, and molecular modulators) are defined and what emerging technologies (perfusable scaffold, tumor stiffness, supporting cells within tumors and complex patterning) can be utilized to better mimic native-like breast cancer microenvironments. Furthermore, this review emphasizes biophysical properties that differ between primary tumor ECM and tissue sites of metastatic lesions with a focus on matrix modulation of cancer stem cells, providing a rationale for investigation of underexplored ECM proteins that could alter patient prognosis. To engineer breast cancer microenvironments, we categorized technologies into two groups: (1) biochemical factors modulating breast cancer cell-ECM interactions and (2) 3D bioprinting methods and its applications to model breast cancer microenvironments. Biochemical factors include matrix-associated proteins, soluble factors, ECMs, and synthetic biomaterials. For the application of 3D bioprinting, we discuss the transition of 2D patterning to 3D scaffolding with various bioprinting technologies to implement biophysical cues to model breast cancer microenvironments.

Extracellular matrices (ECMs) are challenging design targets for materials synthesis because they serve multiple biological roles, and they are composed of multiple molecular constituents. In addition, their composition and activities are dynamic and variable between tissues, and they are difficult to study mechanistically in physiological contexts. Nevertheless, the design of synthetic ECMs is a central consideration in applications such as regenerative medicine and 3D cell culture. In order to produce synthetic matrices having both multi-component construction and high levels of compositional definition, strategies based on molecular self-assembly are receiving increasing interest. These approaches are described in this tutorial reviewand compared with the structures and processes in native ECMs that serve as their inspiration. [ABSTRACT FROM AUTHOR]

Extracellular matrices (ECMs) are challenging design targets for materials synthesis because they serve multiple biological roles, and they are composed of multiple molecular constituents. In addition, their composition and activities are dynamic and variable between tissues, and they are difficult to study mechanistically in physiological contexts. Nevertheless, the design of synthetic ECMs is a central consideration in applications such as regenerative medicine and 3D cell culture. In order to produce synthetic matrices having both multi-component construction and high levels of compositional definition, strategies based on molecular self-assembly are receiving increasing interest. These approaches are described in this tutorial reviewand compared with the structures and processes in native ECMs that serve as their inspiration. [ABSTRACT FROM AUTHOR]

Antioxidant therapies are of interest in the prevention and management of ocular disorders such as cataracts. Although an active area of interest, topical therapy with antioxidants for the treatment of cataracts is complicated by multiple ocular anatomical barriers, product stability, and solubility. Entrapment and delivery of antioxidants with poly(lactic-co-glycolic acid) nanoparticles is a possible solution to these challenges, however, little is known regarding their effects in vitro or in vivo. Our first aim was to investigate the impact of blank and lutein loaded PLGA nanoparticles on viability and development of reactive oxygen species in lens epithelial cells in vitro. Photo-oxidative stress was induced by ultraviolet light exposure with cell viability and reactive oxygen species monitored. Next, an in vivo, selenite model was utilized to induce cataract formation in rodents. Eyes were treated topically with both free lutein and lutein loaded nanoparticles (LNP) at varying concentrations. Eyes were monitored for the development of anterior segment changes and cataract formation. The ability of nanodelivered lutein to reach the anterior segment of the eye was evaluated by liquid chromatography coupled to mass spectrometry of aqueous humor samples and liquid chromatography coupled to tandem mass spectrometry (targeted LC-MS/MS) of lenses. LNP had a minimal impact on the viability of lens epithelial cells during the short exposure timeframe (24 h) and at concentrations < 0.2 μg LNP/μl. A significant reduction in the development of reactive oxygen species was also noted. Animals treated with LNPs at an equivalent lutein concentration of 1,278 μg /mL showed the greatest reduction in cataract scores. Lutein delivery to the anterior segment was confirmed through evaluation of aqueous humor and lens sample evaluation. Topical treatment was not associated with the development of secondary keratitis or anterior uveitis when applied once daily for one week. LNPs may be an effective in the treatment of cataracts.

The plasticity and immunomodulatory capacity of mesenchymal stem cells (MSCs) have spurred clinical use in recent years. However, clinical outcomes vary and many ascribe inconsistency to the tissue source of MSCs. Yet unconsidered is the extent of heterogeneity of individual MSCs from a given tissue source with respect to differentiation potential and immune regulatory function. Here we use single-cell RNA-seq to assess the transcriptional diversity of murine mesenchymal stem cells derived from bone marrow. We found genes associated with MSC multipotency were expressed at a high level and with consistency between individual cells. However, genes associated with osteogenic, chondrogenic, adipogenic, neurogenic and vascular smooth muscle differentiation were expressed at widely varying levels between individual cells. Further, certain genes associated with immunomodulation were also inconsistent between individual cells. Differences could not be ascribed to cycles of proliferation, culture bias or other cellular process, which might alter transcript expression in a regular or cyclic pattern. These results support and extend the concept of lineage priming of MSCs and emphasize caution for in vivo or clinical use of MSCs, even when immunomodulation is the goal, since multiple mesodermal (and even perhaps ectodermal) outcomes are a possibility. Purification might enable shifting of the probability of a certain outcome, but is unlikely to remove multilineage potential altogether.