Rescue of mitochondrial dysfunction through alteration of extracellular matrix composition in barth syndrome cardiac fibroblasts.

Fibroblast-ECM (dys)regulation is associated with a plethora of diseases. The ECM acts as a reservoir of inflammatory factors and cytokines that mediate molecular mechanisms within cardiac cell populations. The role of ECM-mitochondria crosstalk in the development and progression of cardiac disorders remains uncertain.

Spiny mice (Acomys) cells fail to engraft in NOD scid gamma.

Immune cells and stromal cells regulate wound healing and regeneration through complex activation patterns with spatiotemporal variation. The scarless regeneration of Spiny mice (Acomys species) is no exception; differential activation of immune and stromal cell populations seems to play a role in its remarkable regenerative capacity. To elucidate the role and interplay of Acomys immune cells in mammalian regeneration, we sought to create Acomys-Mus chimeras by transplanting bone marrow (BM) from Acomys into NOD Scid Gamma (NSG), a severely immunodeficient mouse line often used in creating humanized mice.

Label-Free Quantification of Microscopic Alignment in Engineered Tissue Scaffolds by Polarized Raman Spectroscopy.

Monitoring of extracellular matrix (ECM) microstructure is essential in studying structure-associated cellular processes, improving cellular function, and for ensuring sufficient mechanical integrity in engineered tissues. This paper describes a novel method to study the microscale alignment of the matrix in engineered tissue scaffolds (ETS) that are usually composed of a variety of biomacromolecules derived by cells. First, a trained loading function was derived from Raman spectra of highly aligned native tissue via principal component analysis (PCA), where prominent changes associated with specific Raman bands (e.

Surgeon confidence in planning total shoulder arthroplasty improves after consulting a clinical decision support tool.

Purpose: Software algorithms are increasingly available as clinical decision support tools (CDSTs) to support shared decision-making. We sought to understand if patient-specific predictions from a CDST would impact orthopedic surgeons' preoperative planning decisions and corresponding confidence.

Methods: We performed a survey study of orthopedic surgeons with at minimum of 2 years of independent shoulder arthroplasty experience.

Biomaterial Design Inspired by Regenerative Research Organisms.

The efficacy of implanted biomaterials is largely dependent on the response of the host's immune and stromal cells. Severe foreign body response (FBR) can impede the integration of the implant into the host tissue and compromise the intended mechanical and biochemical function. Many features of FBR, including late-stage fibrotic encapsulation of implants, parallel the formation of fibrotic scar tissue after tissue injury.

Breathing patterns and CO production in adult spiny mice (Acomys cahirinus).

The spiny mouse (Acomys) is a precocial mammal with unique regenerative abilities. We used whole-body plethysmography to describe the breathing patterns and CO production (VCO) of adult spiny mice (n = 10 male, 10 female) and C57BL/6 mice (n = 9 male, 11 female). During quiet breathing, female but not male spiny mice had lower tidal volumes and CO production vs.

Matrix produced by diseased cardiac fibroblasts affects early myotube formation and function.

The extracellular matrix (ECM) provides both physical and chemical cues that dictate cell function and contribute to muscle maintenance. Muscle cells require efficient mitochondria to satisfy their high energy demand, however, the role the ECM plays in moderating mitochondrial function is not clear. We hypothesized that the ECM produced by stromal cells with mitochondrial dysfunction (Barth syndrome, BTHS) provides cues that contribute to metabolic dysfunction independent of muscle cell health.

Experimental and Computational Models of Transport of Galectin-3 Through Glycosylated Matrix.

Altered extracellular matrix (ECM) production is a hallmark of many fibroproliferative diseases, including certain cancers. The high incidence of glycan-rich components within altered ECM makes the use of glycan-binding proteins such as Galectin-3 (G3) a promising therapeutic strategy. The complexity of ECM as a rich 3D network of proteins with varied glycosylation states makes it challenging to determine the retention of glycan-binding proteins in altered ECM environments.

Label-free quantification of soft tissue alignment by polarized Raman spectroscopy.

The organization of proteins is an important determinant of functionality in soft tissues. However, such organization is difficult to monitor over time in soft tissue with complex compositions. Here, we establish a method to determine the alignment of proteins in soft tissues of varying composition by polarized Raman spectroscopy (PRS).

Spiny mouse (Acomys): an emerging research organism for regenerative medicine with applications beyond the skin.

The spiny mouse (Acomys species) has emerged as an exciting research organism due to its remarkable ability to undergo scarless regeneration of skin wounds and ear punches. Excitingly, Acomys species demonstrate scar-free healing in a wide-range of tissues beyond the skin. In this perspective article, we discuss published findings from a variety of tissues to highlight how this emerging research organism could shed light on numerous clinically relevant human diseases.

Potential Applications of Microfluidics to Acute Kidney Injury Associated with Viral Infection.

The kidneys are susceptible to adverse effects from many diseases, including several that are not tissue-specific. Acute kidney injury is a common complication of systemic diseases such as diabetes, lupus, and certain infections including the novel coronavirus (SARS-CoV-2). Microfluidic devices are an attractive option for disease modeling, offering the opportunity to utilize human cells, control experimental and environmental conditions, and combine with other on-chip devices.

Animal Models to Study Emerging Technologies Against SARS-CoV-2.

New technologies are being developed toward the novel coronavirus SARS-CoV-2 to understand its pathogenesis and transmission, to develop therapeutics and vaccines, and to formulate preventive strategies. Animal models are indispensable to understand these processes and develop and test emerging technologies; however, the mechanism of infection for SARS-CoV-2 requires certain similarities to humans that do not exist in common laboratory rodents. Here, we review important elements of viral infection, transmission, and clinical presentation reflected by various animal models readily available or being developed and studied for SARS-CoV-2 to help bioengineers evaluate appropriate preclinical models for their emerging technologies.

Raman Spectroscopy Methods to Characterize the Mechanical Response of Soft Biomaterials.

Raman spectroscopy has been used extensively to characterize the influence of mechanical deformation on microstructure changes in biomaterials. While traditional piezo-spectroscopy has been successful in assessing internal stresses of hard biomaterials by tracking prominent peak shifts, peak shifts due to applied loads are near or below the resolution limit of the spectrometer for soft biomaterials with moduli in the kilo- to mega-Pascal range. In this Review, in addition to peak shifts, other spectral features (e.

Quantifying cellular forces: Practical considerations of traction force microscopy for dermal fibroblasts.

Traction force microscopy (TFM) is a well-established technique traditionally used by biophysicists to quantify the forces adherent biological cells exert on their microenvironment. As image processing software becomes increasingly user-friendly, TFM is being adopted by broader audiences to quantify contractility of (myo)fibroblasts. While many technical reviews of TFM's computational mechanics are available, this review focuses on practical experimental considerations for dermatology researchers new to cell mechanics and TFM who may wish to implement a higher throughput and less expensive alternative to collagen compaction assays.

Tunable methacrylated hyaluronic acid-based hydrogels as scaffolds for soft tissue engineering applications.

Hyaluronic acid (HA)-based biomaterials have been explored for a number of applications in biomedical engineering, particularly as tissue regeneration scaffolds. Crosslinked forms of HA are more robust and provide tunable mechanical properties and degradation rates that are critical in regenerative medicine; however, crosslinking modalities reported in the literature vary and there are few comparisons of different scaffold properties for various crosslinking approaches. In this study, we offer direct comparison of two methacrylation techniques for HA (glycidyl methacrylate HA [GMHA] or methacrylic anhydride HA [MAHA]).

Treatment of volumetric muscle loss in mice using nanofibrillar scaffolds enhances vascular organization and integration.

Traumatic skeletal muscle injuries cause irreversible tissue damage and impaired revascularization. Engineered muscle is promising for enhancing tissue revascularization and regeneration in injured muscle. Here we fabricated engineered skeletal muscle composed of myotubes interspersed with vascular endothelial cells using spatially patterned scaffolds that induce aligned cellular organization, and then assessed their therapeutic benefit for treatment of murine volumetric muscle loss.

Mechanical Characterization by Mesoscale Indentation: Advantages and Pitfalls for Tissue and Scaffolds.

Regenerative medicine and tissue engineering are hindered by the lack of consistent measurements and standards for the mechanical characterization of tissue and scaffolds. Indentation methods for soft matter are favored because of their compatibility with small, arbitrarily shaped samples, but contact mechanics models required to interpret data are often inappropriate for soft, viscous materials. In this study, we demonstrate indentation experiments on a variety of human biopsies, animal tissue, and engineered scaffolds, and we explore the complexities of fitting analytical models to these data.

Unique behavior of dermal cells from regenerative mammal, the African Spiny Mouse, in response to substrate stiffness.

The African Spiny Mouse (Acomys spp.) is a unique outbred mammal capable of full, scar-free skin regeneration. In vivo, we have observed rapid reepithelialization and deposition of normal dermis in Acomys after wounding.

Quantitative assessment of intestinal stiffness and associations with fibrosis in human inflammatory bowel disease.

Inflammatory bowel disease (IBD) continues to increase in prevalence in industrialized countries. Major complications of IBD include formation of fibrotic strictures, fistulas, reduced absorptive function, cancer risk, and the need for surgery. In other chronic gastrointestinal disease models, stiffness has been shown to precede fibrosis; therefore, stiffness may be a reasonable indicator of progression toward stricture formation in IBD patients.

Viscoelastic properties of human pancreatic tumors and in vitro constructs to mimic mechanical properties.

Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) is almost universally fatal, in large part due to a protective fibrotic barrier generated by tumor-associated stromal (TAS) cells. This barrier is thought to promote cancer cell survival and confounds attempts to develop effective therapies. We present a 3D in vitro system that replicates the mechanical properties of the PDAC microenvironment, representing an invaluable tool for understanding the biology of the disease.

Mechanical characterization of human brain tumors from patients and comparison to potential surgical phantoms.

While mechanical properties of the brain have been investigated thoroughly, the mechanical properties of human brain tumors rarely have been directly quantified due to the complexities of acquiring human tissue. Quantifying the mechanical properties of brain tumors is a necessary prerequisite, though, to identify appropriate materials for surgical tool testing and to define target parameters for cell biology and tissue engineering applications. Since characterization methods vary widely for soft biological and synthetic materials, here, we have developed a characterization method compatible with abnormally shaped human brain tumors, mouse tumors, animal tissue and common hydrogels, which enables direct comparison among samples.

Hypertension-Linked Pathophysiological Alterations in the Gut.

Rationale: Sympathetic nervous system control of inflammation plays a central role in hypertension. The gut receives significant sympathetic innervation, is densely populated with a diverse microbial ecosystem, and contains immune cells that greatly impact overall inflammatory homeostasis. Despite this uniqueness, little is known about the involvement of the gut in hypertension.

Hypertension-linked mechanical changes of rat gut.

Unlabelled: Hypertension is the most prevalent risk factor for cardiovascular disease caused by a persistent increase in arterial blood pressure that has lasting effects on the mechanical properties of affected tissues like myocardium and blood vessels. Our group recently discovered that gut dysbiosis is linked to hypertension in several animal models and humans; however, whether hypertension influences the gut's mechanical properties remains unknown. In this study, we evaluated the hypothesis that hypertension increases fibrosis and thus mechanical properties of the gut.