The lung's health and disease are significantly influenced by the extracellular matrix (ECM). In lung bioengineering, collagen, the principle component of the lung's extracellular matrix, is commonly used for constructing in vitro and organotypic models of lung diseases and serves as a versatile scaffold material. Populus microbiome A hallmark of fibrotic lung disease is the drastic modification of collagen's structure and properties, ultimately resulting in the formation of dysfunctional, scarred tissue, with collagen serving as a key diagnostic measure. Collagen's central role in lung disease demands rigorous quantification, the precise determination of its molecular attributes, and three-dimensional visualization, all essential for the development and assessment of translational lung research models. A comprehensive overview of currently available methods for quantifying and characterizing collagen is presented in this chapter, including the underlying detection principles, advantages, and disadvantages of each.
Since 2010, research on lung-on-a-chip technology has demonstrably progressed, culminating in significant advancements in recreating the cellular ecosystem of healthy and diseased alveoli. The launch of the first lung-on-a-chip products in the marketplace has inspired innovative designs to further replicate the alveolar barrier's intricacies, ushering in a new era of improved lung-on-chip technology. Hydrogel membranes, composed of proteins from the lung extracellular matrix, are replacing the earlier PDMS polymeric membranes, exceeding them in both chemical and physical qualities. The alveolar environment's structural features, namely the dimensions, three-dimensional layouts, and arrangements of the alveoli, are replicated. Altering the properties of this microenvironment enables fine-tuning of alveolar cell phenotypes and the faithful reproduction of air-blood barrier functions, thus facilitating the simulation of complex biological processes. Biological data previously unobtainable by conventional in vitro systems are now possible through the application of lung-on-a-chip technologies. The now-reproducible consequence of a damaged alveolar barrier is pulmonary edema leakage, coupled with the barrier stiffening effect of over-accumulated extracellular matrix proteins. On the condition that the obstacles presented by this innovative technology are overcome, it is certain that many areas of application will experience considerable growth.
Gas exchange takes place within the lung parenchyma, a structure comprising gas-filled alveoli, intricate vasculature, and supportive connective tissue, and this area is centrally involved in the diverse spectrum of chronic lung diseases. In-vitro models of lung tissue, therefore, present valuable platforms for research into lung biology in both health and disease. Representing a tissue of this complexity necessitates incorporating several elements: biochemical cues originating from the extracellular space, precisely arranged cellular interactions, and dynamic mechanical inputs, like the cyclic stretch of respiration. Model systems replicating one or more features of lung parenchyma and their contribution to scientific progress are surveyed in this chapter. Considering the utility of synthetic and naturally derived hydrogel materials, precision-cut lung slices, organoids, and lung-on-a-chip devices, we analyze the strengths, limitations, and potential future directions of these engineered platforms.
Within the mammalian lung, the arrangement of its airways dictates the air's course, leading to the distal alveolar region crucial for gas exchange. The lung mesenchyme's specialized cells synthesize the extracellular matrix (ECM) and growth factors crucial for lung architecture. Historically, the heterogeneity of mesenchymal cell subtypes was challenging to define due to the cells' ambiguous morphologies, the overlapping expression of various protein markers, and the restricted selection of useful cell-surface molecules for isolation. The lung mesenchyme, as evidenced by single-cell RNA sequencing (scRNA-seq) and genetic mouse models, displays a range of functionally and transcriptionally diverse cell types. Bioengineering approaches, by mirroring tissue structure, help to understand the operation and regulation within mesenchymal cell types. thoracic medicine Fibroblasts' unique capabilities in mechanosignaling, force generation, extracellular matrix production, and tissue regeneration are highlighted by these experimental approaches. https://www.selleck.co.jp/products/Y-27632.html A review of lung mesenchymal cell biology, along with methods for evaluating their functions, will be presented in this chapter.
A key concern in trachea replacement surgery arises from the contrasting mechanical properties of the native tracheal tissue and the replacement material; this variance is frequently a primary contributor to implant failure both in the body and during clinical procedures. Each structural component within the trachea has a different purpose, collectively working to uphold the trachea's stability. The hyaline cartilage rings, smooth muscle, and annular ligament of the trachea, in their horseshoe configuration, collectively form an anisotropic tissue, capable of longitudinal expansion and lateral firmness. Subsequently, any tracheal replacement needs to be mechanically sturdy enough to withstand the pressure shifts inside the chest cavity which happen during the breathing cycle. Conversely, the structures' ability to deform radially is essential for adapting to variations in cross-sectional area, as required during the act of coughing and swallowing. The creation of tracheal biomaterial scaffolds faces a major obstacle due to the intricate characteristics of native tracheal tissues and the absence of standardized protocols for precisely measuring the biomechanics of the trachea, which is fundamental for guiding implant design. Within this chapter, we analyze the pressures influencing the trachea, elucidating their effect on tracheal construction and the biomechanical properties of the trachea's principal structural components, and methods to mechanically assess them.
The respiratory tree's large airways are crucial for both immunoprotection and the mechanics of breathing. Large airways, from a physiological standpoint, are essential for conveying substantial quantities of air to and from the alveolar gas exchange surfaces. Within the respiratory tree, air's path is fragmented as it moves from the initial large airways, branching into smaller bronchioles, and ultimately reaching the alveoli. A key immunoprotective function of the large airways is their role as an initial barrier against inhaled particles, bacteria, and viruses. The large airways' immunity is significantly enhanced by the production of mucus and the function of the mucociliary clearance mechanism. From the standpoint of both basic physiology and engineering principles, each of these lung attributes is essential for regenerative medicine. This chapter undertakes an engineering-based study of the large airways, with an emphasis on current models and prospective advancements in modeling and repair strategies.
By acting as a physical and biochemical barrier, the airway epithelium is essential in preventing lung infiltration by pathogens and irritants, maintaining tissue homeostasis, and regulating innate immunity. The constant inhalation and exhalation of air during respiration exposes the epithelium to a wide array of environmental stressors. These insults, when severe and persistent, ultimately provoke inflammation and infection. In order to function as an effective barrier, the epithelium requires the simultaneous processes of mucociliary clearance, immune surveillance and its regenerative capacity following any kind of harm. The cells comprising the airway epithelium and the niche they reside in are responsible for these functions. Engineering both physiological and pathological models of the proximal airways hinges upon the creation of complex structures comprised of the airway epithelium, submucosal gland layer, extracellular matrix, and essential niche cells, including smooth muscle cells, fibroblasts, and immune cells. Airway structure-function relationships are examined in this chapter, alongside the challenges in developing complex, engineered models of the human airway.
For vertebrate development, transient embryonic progenitors, specific to tissues, are vital cell types. The respiratory system's development is driven by the differentiation potential of multipotent mesenchymal and epithelial progenitors, creating the wide array of cell types found in the adult lungs' airways and alveolar structures. Employing mouse genetic models, including lineage tracing and loss-of-function techniques, researchers have uncovered signaling pathways regulating the proliferation and differentiation of embryonic lung progenitors, and the transcription factors crucial to lung progenitor cell identity. Particularly, respiratory progenitors, expanded outside the body from pluripotent stem cells, present innovative, readily analyzed, and highly reliable systems to examine the mechanistic underpinnings of cell fate decisions and developmental processes. Profounding our understanding of embryonic progenitor biology, we approach the realization of in vitro lung organogenesis, and the applications it presents to developmental biology and medicine.
For the last ten years, efforts have been concentrated on re-creating the structural design and cell-cell exchanges that characterise organs within living organisms [1, 2]. While in vitro reductionist approaches effectively dissect precise signaling pathways, cellular interactions, and responses to chemical and physical stimuli, more intricate model systems are necessary to examine tissue-scale physiology and morphogenesis. Significant improvements in the creation of in vitro lung development models have allowed for a deeper understanding of cell-fate determination, gene regulatory pathways, sexual variations, structural complexity, and the effect of mechanical forces on lung organogenesis [3-5].