No abstract

This article presents a review of the fluid dynamics, flow-structure interactions, and acoustics associated with human phonation and speech. Our voice is produced through the process of phonation in the larynx, and an improved understanding of the underlying physics of this process is essential to advancing the treatment of voice disorders. Insights into the physics of phonation and speech can also contribute to improved vocal training and the development of new speech compression and synthesis schemes. This article introduces the key biomechanical features of the laryngeal physiology, reviews the basic principles of voice production, and summarizes the progress made over the past half-century in understanding the flow physics of phonation and speech. Laryngeal pathologies, which significantly enhance the complexity of phonatory dynamics, are discussed. After a thorough examination of the state of the art in computational modeling and experimental investigations of phonatory biomechanics, we present a synopsis of the pacing issues in this arena and an outlook for research in this fascinating subject. 437

3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, to realize the true potential of 3D bioprinted tissues for clinical use requires the fabrication of an interconnected and effective vascular network. Solving this challenge is critical, as human tissue relies on an adequate network of blood vessels to transport oxygen, nutrients, other chemicals, biological factors and waste, in and out of the tissue. Here, we have successfully designed and printed a series of novel 3D bone scaffolds with both bone formation supporting structures and highly interconnected 3D microvascular mimicking channels, for efficient and enhanced osteogenic bone regeneration as well as vascular cell growth. Using a chemical functionalization process, we have conjugated our samples with nano hydroxyapatite (nHA), for the creation of novel micro and nano featured devices for vascularized bone growth. We evaluated our scaffolds with mechanical testing, hydrodynamic measurements and in vitro human mesenchymal stem cell (hMSC) adhesion (4 h), proliferation (1, 3 and 5 d) and osteogenic differentiation (1, 2 and 3 weeks). These tests confirmed bone-like physical properties and vascular-like flow profiles, as well as demonstrated enhanced hMSC adhesion, proliferation and osteogenic differentiation. Additional in vitro experiments with human umbilical vein endothelial cells also demonstrated improved vascular cell growth, migration and organization on micro-nano featured scaffolds.

4D printing is a highly innovative additive manufacturing process for fabricating smart structures with the ability to transform over time. Significantly different from regular 4D printing techniques, this study focuses on creating novel 4D hierarchical micropatterns using a unique photolithographic-stereolithographic-tandem strategy (PSTS) with smart soybean oil epoxidized acrylate (SOEA) inks for effectively regulating human bone marrow mesenchymal stem cell (hMSC) cardiomyogenic behaviors. The 4D effect refers to autonomous conversion of the surficial-patterned scaffold into a predesigned construct through an external stimulus delivered immediately after printing. Our results show that hMSCs actively grew and were highly aligned along the micropatterns, forming an uninterrupted cellular sheet. The generation of complex patterns was evident by triangular and circular outlines appearing in the scaffolds. This simple, yet efficient, technique was validated by rapid printing of scaffolds with well-defined and consistent micro-surface features. A 4D dynamic shape change transforming a 2-D design into flower-like structures was observed. The printed scaffolds possessed a shape memory effect beyond the 4D features. The advanced 4D dynamic feature may provide seamless integration with damaged tissues or organs, and a proof of concept 4D patch for cardiac regeneration was demonstrated for the first time. The 4D-fabricated cardiac patch showed significant cardiomyogenesis confirmed by immunofluorescence staining and qRT-PCR analysis, indicating its promising potential in future tissue and organ regeneration applications.

No abstract

A theoretical flow solution is presented for predicting the pressure distribution along the vocal fold walls arising from asymmetric flow that forms during the closing phases of speech. The resultant wall jet was analyzed using boundary layer methods in a non-inertial reference frame attached to the moving wall. A solution for the near-wall velocity profiles on the flow wall was developed based on a Falkner-Skan similarity solution and it was demonstrated that the pressure distribution along the flow wall is imposed by the velocity in the inviscid core of the wall jet. The method was validated with experimental velocity data from 7.5 times life-size vocal fold models, acquired for varying flow rates and glottal divergence angles. The solution for the asymmetric pressures was incorporated into a widely used two-mass model of vocal fold oscillation with a coupled acoustical model of sound propagation. Asymmetric pressure loading was found to facilitate glottal closure, which yielded only slightly higher values of maximum flow declination rate and radiated sound, and a small decrease in the slope of the spectral tilt. While the impact on symmetrically tensioned vocal folds was small, results indicate the effect becomes more significant for asymmetrically tensioned vocal folds.

Osteochondral tissue has a complex graded structure where biological, physiological, and mechanical properties vary significantly over the full thickness spanning from the subchondral bone region beneath the joint surface to the hyaline cartilage region at the joint surface. This presents a significant challenge for tissue-engineered structures addressing osteochondral defects. Fused deposition modeling (FDM) 3D bioprinters present a unique solution to this problem. The objective of this study is to use FDM-based 3D bioprinting and nanocrystalline hydroxyapatite for improved bone marrow human mesenchymal stem cell (hMSC) adhesion, growth, and osteochondral differentiation. FDM printing parameters can be tuned through computer aided design and computer numerical control software to manipulate scaffold geometries in ways that are beneficial to mechanical performance without hindering cellular behavior. Additionally, the ability to fine-tune 3D printed scaffolds increases further through our investment casting procedure which facilitates the inclusion of nanoparticles with biochemical factors to further elicit desired hMSC differentiation. For this study, FDM was used to print investment-casting molds innovatively designed with varied pore distribution over the full thickness of the scaffold. The mechanical and biological impacts of the varied pore distributions were compared and evaluated to determine the benefits of this physical manipulation. The results indicate that both mechanical properties and cell performance improve in the graded pore structures when compared to homogeneously distributed porous and non-porous structures. Differentiation results indicated successful osteogenic and chondrogenic manipulation in engineered scaffolds.

Blood vessel damage resulting from trauma or diseases presents a serious risk of morbidity and mortality. Although synthetic vascular grafts have been successfully commercialized for clinical use, they are currently only readily available for large-diameter vessels (>6 mm). Small-diameter vessel (<6 mm) replacements, however, still present significant clinical challenges worldwide. The primary objective of this study is to create novel, tunable, small-diameter blood vessels with biomimetic two distinct cell layers [vascular endothelial cell (VEC) and vascular smooth muscle cell (VSMC)] using an advanced coaxial 3D-bioplotter platform. Specifically, the VSMCs were laden in the vessel wall and VECs grew in the lumen to mimic the natural composition of the blood vessel. First, a novel bioink consisting of VSMCs laden in gelatin methacryloyl (GelMA)/ polyethylene(glycol)diacrylate/alginate and lyase was designed. This specific design is favorable for nutrient exchange in an ambient environment and simultaneously improves laden cell proliferation in the matrix pore without the space restriction inherent with substance encapsulation. In the vessel wall, the laden VSMCs steadily grew as the alginate was gradually degraded by lyase leaving more space for cell proliferation in matrices. Through computational fluid dynamics simulation, the vessel demonstrated significantly perfusable and mechanical properties under various flow velocities, flow viscosities, and temperature conditions. Moreover, both VSMCs in the scaffold matrix and VECs in the lumen steadily proliferated over time creating a significant two-cell-layered structure. Cell proliferation was confirmed visually through staining the markers of alphasmooth muscle actin and cluster of differentiation 31, commonly tied to angiogenesis phenomena, in the vessel matrices and lumen, respectively. Furthermore, the results were confirmed quantitatively through gene analysis which suggested good angiogenesis expression in the blood vessels. This study demonstrated that the printed blood vessels with two distinct cell layers of VECs and VSMCs could be potential candidates for clinical small-diameter blood vessel replacement applications.