Fibro-adipogenesis in Injured Rotator Cuff Muscle

Purpose of Review Fibro-adipogenic progenitors were first characterized in 2010 and later found to contribute significantly to muscle regeneration and mediate degenerative changes in muscle following injury. These progenitors were also found to have an influence on the rotator cuff muscle’s response to chronic injury which is defined by fibrosis accompanied by massive fatty degeneration. The purpose of this review is to highlight progenitor cells, their contribution to fibro-adipogenesis in rotator cuff tissue, and the factors influencing fibro-adipogenesis in this tissue. Recent Findings Fibro-adipogenic progenitors are a key mediator of the fatty infiltration notably prevalent in rotator cuff injury. Relative to other muscle groups, the rotator cuff has relatively high rates of fibro-adipogenesis following massive chronic rotator cuff tears. This may be linked to the pre-injury density of fibro-adipogenic progenitors in muscle tissue affecting post-injury levels of fibro-adipogenesis. In addition, suprascapular nerve injury in rat models of rotator cuff tears has demonstrated worse, histologic, and biomechanical properties and lower healing rates of rotator cuff repairs. However, fatty infiltration in the rotator cuff following suprascapular nerve compression has been shown to be reversible following release of the nerve compression. Summary The fibro-adipogenic response to acute and chronic injury in rotator cuff tissue is determined by a complex array of factors including progenitor cell influence, transcriptional pathways, chronicity of the injury, anatomic location of injury, microenvironmental influences, and the severity of nerve involvement. Elucidating the complex interactions of these factors will provide potential targets for therapeutic intervention in vivo.

Extracellular Matrix Remodeling in Chronic Liver Disease

Purpose of the Review This review aims to summarize the current knowledge of the extracellular matrix remodeling during hepatic fibrosis. We discuss the diverse interactions of the extracellular matrix with hepatic cells and the surrounding matrix in liver fibrosis, with the focus on the molecular pathways and the mechanisms that regulate extracellular matrix remodeling. Recent Findings The extracellular matrix not only provides structure and support for the cells, but also controls cell behavior by providing adhesion signals and by acting as a reservoir of growth factors and cytokines. Summary Hepatic fibrosis is characterized by an excessive accumulation of extracellular matrix. During fibrogenesis, the natural remodeling process of the extracellular matrix varies, resulting in the excessive accumulation of its components, mainly collagens. Signals released by the extracellular matrix induce the activation of hepatic stellate cells, which are the major source of extracellular matrix and most abundant myofibroblasts in the liver. Graphical abstract

Biomechanical Regulation of Hematopoietic Stem Cells in the Developing Embryo

Purpose of Review The contribution of biomechanical forces to hematopoietic stem cell (HSC) development in the embryo is a relatively nascent area of research. Herein, we address the biomechanics of the endothelial-to-hematopoietic transition (EHT), impact of force on organelles, and signaling triggered by extrinsic forces within the aorta-gonad-mesonephros (AGM), the primary site of HSC emergence. Recent Findings Hemogenic endothelial cells undergo carefully orchestrated morphological adaptations during EHT. Moreover, expansion of the stem cell pool during embryogenesis requires HSC extravasation into the circulatory system and transit to the fetal liver, which is regulated by forces generated by blood flow. Findings from other cell types also suggest that forces external to the cell are sensed by the nucleus and mitochondria. Interactions between these organelles and the actin cytoskeleton dictate processes such as cell polarization, extrusion, division, survival, and differentiation. Summary Despite challenges of measuring and modeling biophysical cues in the embryonic HSC niche, the past decade has revealed critical roles for mechanotransduction in governing HSC fate decisions. Lessons learned from the study of the embryonic hematopoietic niche promise to provide critical insights that could be leveraged for improvement in HSC generation and expansion ex vivo.

3D Bioprinting of Cardiovascular Tissues for In Vivo and In Vitro Applications Using Hybrid Hydrogels Containing Silk Fibroin: State of the Art and Challenges

Purpose of Review 3D bioprinting of cardiovascular tissues for in vitro and in vivo applications is currently investigated as a potential solution to better mimic the microenvironment typical of the human heart. However, optimal cell viability and tissue vascularization remain two of the main challenges in this regard. Silk fibroin (SF) as a natural biomaterial with unique features supports cell survival and tissue vascularization. This review aims to evaluate the potential of hydrogels containing SF in 3D bioprinting of cardiac tissue that better recapitulate the native cardiac microenvironment. Recent Findings SF hydrogels spontaneously develop nanocrystals, which limit their use for 3D bioprinting applications. Nevertheless, the printability of SF is improved in hybrid hydrogels by mixing it with other natural polymers (such as alginate and gelatin). This is achieved by adding SF with other polymers or by crosslinking it by peroxidase catalysis (i.e., with alginate). Compared to only SF-based hydrogels, hybrid hydrogels provide a durable bioprinted construct with improved mechanical stability and biological properties. To date, studies using cardiac cells in bioprinted SF constructs are yet to be performed. Summary Mixing SF with other polymers in bioprinted hybrid hydrogels improves the printability and durability of 3D bioprinted tissues. Studies using these hydrogels with cardiac cells will be required to evaluate the biocompatibility of SF hybrid hydrogels and to establish their potential use for cardiovascular applications.