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Tendon mimetic scaffolds that recreate the tendon hierarchical structure and niche have increasing potential to fully restore tendon functionality. However, most scaffolds lack biofunctionality to boost the tenogenic differentiation of stem cells. In this study, we assessed the role of platelet-derived extracellular vesicles (EVs) in stem cells' tenogenic commitment using a 3D bioengineered in vitro tendon model. First, we relied on fibrous scaffolds coated with collagen hydrogels encapsulating human adipose-derived stem cells (hASCs) to bioengineer our composite living fibers. We found that the hASCs in our fibers showed high elongation and cytoskeleton anisotropic organization, typical of tenocytes. Moreover, acting as biological cues, platelet-derived EVs boosted the hASCs' tenogenic commitment, prevented phenotypic drift, enhanced the deposition of the tendon-like extracellular matrix, and induced lower collagen matrix contraction. In conclusion, our living fibers provided an in vitro system for tendon tissue engineering, allowing us to study not only the tendon microenvironment but also the influence of biochemical cues on stem cell behavior. More importantly, we showed that platelet-derived EVs are a promising biochemical tool for tissue engineering and regenerative medicine applications that are worthy of further exploration, as paracrine signaling might potentiate tendon repair and regeneration. [ABSTRACT FROM AUTHOR]

Asymmetric rolling is a forming process that has raised interest among researchers due to the significant improvements it introduces to the mechanical response of metals. The main objective of the present work is to perform a numerical study on asymmetrical rolled aluminum alloy sheets to identify and correlate the effect of the additional shear strain component on the material formability, tensile strength, and texture orientations development during multi-pass metal forming. Conventional (CR), asymmetric continuous (ASR-C), and asymmetric rolling-reverse (ASR-R) simulations were carried out using the visco-plastic self-consistent (VPSC) code. For the ASR process, two different shear strain values were prescribed. Moreover, two hardening models were considered: a Voce-type law and a dislocation-based model that accounts for strain path changes during metal forming. Results showed that the ASR process is able to improve the plastic strain ratio and tensile strength. The ASR-C revealed better results, although the expected shear orientations are only evident in the ASR-R process. [ABSTRACT FROM AUTHOR]

Tendon injuries represent over 30–50% of musculoskeletal disorders worldwide, yet the available therapies do not provide complete tendon repair/regeneration and full functionality restoring. Extracellular vesicles (EVs), membrane-enclosed nanoparticles, have emerged as the next breakthrough in tissue engineering and regenerative medicine to promote endogenous tissue regeneration. Here, we developed a 3D human in vitro model mimicking the signature of pathological tendon and used it to evaluate the influence that different platelet-derived EVs might have in tendon tissue repair mechanisms. For this, different EV populations isolated from platelets, small EVs (sEVs) and medium EVs (mEVs), were added to the culture media of human tendon-derived cells (hTDCs) cultured on isotropic nanofibrous scaffolds. The platelet-derived EVs increased the expression of tenogenic markers, promoted a healthy extracellular matrix (ECM) remodeling, and the synthesis of anti-inflammatory mediators. These findings suggest that platelet EVs provided relevant biochemical cues that potentiated a recovery of hTDCs phenotype from a diseased to a healthy state. Thus, this study opens new perspectives for the translation of platelet-derived EVs as therapeutics. [ABSTRACT FROM AUTHOR]

Several studies on asymmetric rolling processes use the Finite Element Method (FEM) to predict material deformation and optimize process parameters, such as rolls' forces and torques. Early studies focused on the observation and measure of curvature effects due to the asymmetric conditions. However, these models could not predict mechanical behavior associated with the texture evolution during the rolling processes. More recent studies introduced crystal plasticity (CP) models into the FEM to analyze and quantify the texture evolution during plastic forming. However, these coupled techniques need more investigation, especially concerning the mechanical behavior of the material during and after multi-stage ASR procedures. The purpose of this work is to present an up-to-date literature review on the implementation of asymmetric rolling processes in finite element analysis. It shows a summarized overview of the asymmetric rolling model parameters from different authors and gives a brief description of the crystallographic models used in their studies. In the end, some suggestions for future work dedicated to the analysis of ASR through FEM are given. [ABSTRACT FROM AUTHOR]

In the field of tissue engineering and regenerative medicine, hydrogels are used as biomaterials to support cell attachment and promote tissue regeneration due to their unique biomimetic characteristics. The use of natural-origin materials significantly influenced the origin and progress of the field due to their ability to mimic the native tissues' extracellular matrix and biocompatibility. However, the majority of these natural materials failed to provide satisfactory cues to guide cell differentiation toward the formation of new tissues. In addition, the integration of technological advances, such as 3D printing, microfluidics and nanotechnology, in tissue engineering has obsoleted the first generation of natural-origin hydrogels. During the last decade, a new generation of hydrogels has emerged to meet the specific tissue necessities, to be used with state-of-the-art techniques and to capitalize the intrinsic characteristics of natural-based materials. In this review, we briefly examine important hydrogel crosslinking mechanisms. Then, the latest developments in engineering natural-based hydrogels are investigated and major applications in the field of tissue engineering and regenerative medicine are highlighted. Finally, the current limitations, future challenges and opportunities in this field are discussed to encourage realistic developments for the clinical translation of tissue engineering strategies. [ABSTRACT FROM AUTHOR]