Pregnancy and age differentially affect stiffness, injury susceptibility, and composition of murine uterosacral ligaments.

Pelvic organ prolapse is a debilitating condition that diminishes quality of life, and it has been linked to pregnancy and aging. Injury of the uterosacral ligaments (USLs), which provide apical support to the pelvic organs, is a major cause of uterine prolapse. In this study, we examined the effect of pregnancy and age on the apparent elastic modulus, susceptibility to collagen damage, and extracellular matrix (ECM) composition of the murine USL.

Altered post-fracture systemic bone loss in a mouse model of osteocyte dysfunction.

Femur fracture leads to loss of bone at uninjured skeletal sites, which may increase risk of subsequent fracture. Osteocytes, the most abundant bone cells, can directly resorb bone matrix and regulate osteoclast and osteoblast activity, but their role in systemic bone loss after fracture remains poorly understood. In this study we used a transgenic (TG+) mouse model that overexpresses human B-cell lymphoma 2 (BCL-2) in osteoblasts and osteocytes.

Controlled Mechanical Property Gradients Within a Digital Light Processing Printed Hydrogel-Composite Osteochondral Scaffold.

Tissue engineered scaffolds are needed to support physiological loads and emulate the micrometer-scale strain gradients within tissues that guide cell mechanobiological responses. We designed and fabricated micro-truss structures to possess spatially varying geometry and controlled stiffness gradients. Using a custom projection microstereolithography (μSLA) system, using digital light projection (DLP), and photopolymerizable poly(ethylene glycol) diacrylate (PEGDA) hydrogel monomers, three designs with feature sizes < 200 μm were formed: (1) uniform structure with 1 MPa structural modulus ( ) designed to match equilibrium modulus of healthy articular cartilage, (2)  = 1 MPa gradient structure designed to vary strain with depth, and (3) osteochondral bilayer with distinct cartilage (  = 1 MPa) and bone (  = 7 MPa) layers.

Multi-scale cortical bone traits vary in females and males from two mouse models of genetic diversity.

Understanding the genetic basis of cortical bone traits can allow for the discovery of novel genes or biological pathways regulating bone health. Mice are the most widely used mammalian model for skeletal biology and allow for the quantification of traits that cannot easily be evaluated in humans, such as osteocyte lacunar morphology. The goal of our study was to investigate the effect of genetic diversity on multi-scale cortical bone traits of 3 long bones in skeletally-mature mice.

Bone Structure and Turnover in Postmenopausal Women With Long-Standing Type 1 Diabetes.

Compromised bone structural and mechanical properties are implicated in the increased fracture risk in type 1 diabetes (T1D). We investigated bone structure and turnover by histomorphometry in postmenopausal women with T1D and controls without diabetes using tetracycline double-labeled transiliac bone biopsy. After in vivo tetracycline double labeling, postmenopausal women with T1D of at least 10 years and without diabetes underwent transiliac bone biopsy.

In-person and virtual adaptation of an interprofessional palliative care communications skills training course for pediatric oncology clinicians.

Purpose: Effective, empathic communication is crucial for pediatric oncology clinicians when discussing palliative and end-of-life (PC/EOL) care with parents of children with cancer. Unfortunately, many parents report inadequate communication at these distressing times. This study evaluates the communication skills training (CST) clinicians received to deliver a PC/EOL communication intervention as part of a multi-site randomized-controlled trial (RCT).

Multi-Scale Cortical Bone Traits Vary in Two Mouse Models of Genetic Diversity.

Understanding the genetic basis of cortical bone traits can allow for the discovery of novel genes or biological pathways regulating bone health. Mice are the most widely used mammalian model for skeletal biology and allow for the quantification of traits that can't easily be evaluated in humans, such as osteocyte lacunar morphology. The goal of our study was to investigate the effect of genetic diversity on multi-scale cortical bone traits of three long bones in skeletally-mature mice.

Isolation and Characterization of the Murine Uterosacral Ligaments and Pelvic Floor Organs.

Pelvic organ prolapse (POP) is a condition that affects the integrity, structure, and mechanical support of the pelvic floor. The organs in the pelvic floor are supported by different anatomical structures, including muscles, ligaments, and pelvic fascia. The uterosacral ligament (USL) is a critical load-bearing structure, and injury to the USL results in a higher risk of developing POP.

Poroviscoelasto-plasticity of agarose-based hydrogels.

Agarose gels are excellent candidates for tissue engineering as they are tunable, viscoelastic, and show a pronounced strain-stiffening response. These characteristics make them ideal to create environments to grow cells and develop tissues. As in many other biopolymers, viscoelasticity and poroelasticity coexist as time-dependent behaviors in agarose gels.

Transcriptome-wide association study and eQTL colocalization identify potentially causal genes responsible for human bone mineral density GWAS associations.

Genome-wide association studies (GWASs) for bone mineral density (BMD) in humans have identified over 1100 associations to date. However, identifying causal genes implicated by such studies has been challenging. Recent advances in the development of transcriptome reference datasets and computational approaches such as transcriptome-wide association studies (TWASs) and expression quantitative trait loci (eQTL) colocalization have proven to be informative in identifying putatively causal genes underlying GWAS associations.

A 3D printed mimetic composite for the treatment of growth plate injuries in a rabbit model.

Growth plate injuries affecting the pediatric population may cause unwanted bony repair tissue that leads to abnormal bone elongation. Clinical treatment involves bony bar resection and implantation of an interpositional material, but success is limited and the bony bar often reforms. No treatment attempts to regenerate the growth plate cartilage.

The effects of prostaglandin E2 on gene expression of IDG-SW3-derived osteocytes in 2D and 3D culture.

Prostaglandin E (PGE) is a key signaling molecule produced by osteocytes in response to mechanical loading, but its effect on osteocytes is less understood. This work examined the effect of PGE on IDG-SW3-derived osteocytes in standard 2D culture (collagen-coated tissue culture polystyrene) and in a 3D degradable poly(ethylene glycol) hydrogel. IDG-SW3 cells were differentiated for 35 days into osteocytes in 2D and 3D cultures.

Effects of Kinetic Chain Length on the Degradation of Poly(β-amino ester)-Based Networks and Use in 3D Printing by Projection Microstereolithography.

Poly(β-amino ester)-diacrylates (PBAE-dAs) are promising resins for three-dimensional (3D) printing. This study investigated the degradation of two PBAEs with different chemistries and kinetic chain lengths. PBAE-dA monomers were synthesized from benzhydrazide and poly(ethylene glycol) (A6) or butanediol (B6) diacrylate and then photopolymerized with pentaerythritol tetrakis(3-mercaptopropionate), which formed thiol-polyacrylate kinetic chains.

Results of the phase IIa RADICAL trial of the FGFR inhibitor AZD4547 in endocrine resistant breast cancer.

We conducted a phase IIa, multi-centre, open label, single arm study (RADICAL; NCT01791985) of AZD4547 (a potent and selective inhibitor of Fibroblast Growth Factor Receptor (FGFR)-1, 2 and 3 receptor tyrosine kinases) administered with anastrozole or letrozole in estrogen receptor positive metastatic breast cancer patients who had become resistant to aromatase inhibitors. After a safety run-in study to assess safety and tolerability, we recruited 52 patients. The primary endpoint was change in tumour size at 12 weeks, and secondary endpoints were to assess response at 6 weeks, 20 weeks and every 8 weeks thereafter and tolerability of the combined treatment.

Material properties and strain distribution patterns of bovine growth plate cartilage vary with anatomic location and depth.

The aim of this study was to assess the bulk material properties and depth-dependent strain distribution of bovine growth plate cartilage. We hypothesized that both moduli and strain distribution are highly depth-, orientation-, and location-dependent. Bovine proximal tibiae (1-month-old) were sliced along the sagittal and coronal planes to create ∼ 4 mm samples.

The heterogeneous mechanical properties of adolescent growth plate cartilage: A study in rabbit.

The growth plate is a cartilaginous tissue that functions to lengthen bones in children. When fractured, however, the growth plate can lose this critical function. Our understanding of growth plate fracture and mechanobiology is currently hindered by sparse information on the growth plate's microscale spatial gradients in mechanical properties.

The behavioral effects of gestational and lactational benzo[a]pyrene exposure vary by sex and genotype in mice with differences at the Ahr and Cyp1a2 loci.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) and known carcinogen in the Top 10 on the United States' list of priority pollutants. Humans are exposed through a variety of sources including tobacco smoke, grilled foods and fossil fuel combustion. Recent studies of children exposed to higher levels of PAHs during pregnancy and early life have identified numerous adverse effects on the brain and behavior that persist into school age and adolescence.

Recellularization and Integration of Dense Extracellular Matrix by Percolation of Tissue Microparticles.

Unlabelled: Cells embedded in the extracellular matrix of tissues play a critical role in maintaining homeostasis while promoting integration and regeneration following damage or disease. Emerging engineered biomaterials utilize decellularized extracellular matrix as a tissue-specific support structure; however, many dense, structured biomaterials unfortunately demonstrate limited formability, fail to promote cell migration, and result in limited tissue repair. Here, we developed a reinforced composite material of densely packed acellular extracellular matrix microparticles in a hydrogel, termed , that can be molded and crosslinked to mimic native tissue architecture.

Genetic variability affects the skeletal response to immobilization in founder strains of the diversity outbred mouse population.

Mechanical unloading decreases bone volume and strength. In humans and mice, bone mineral density is highly heritable, and in mice the response to changes in loading varies with genetic background. Thus, genetic variability may affect the response of bone to unloading.

Application of machine learning classifiers for microcomputed tomography data assessment of mouse bone microarchitecture.

The current standard approach for analyzing cortical bone structure and trabecular bone microarchitecture from micro-computed tomography (microCT) is through classic parametric (e.g., ANOVA, Student's T-test) and nonparametric (e.

Biomimetic and mechanically supportive 3D printed scaffolds for cartilage and osteochondral tissue engineering using photopolymers and digital light processing.

Successful 3D scaffold designs for musculoskeletal tissue engineering necessitate full consideration of the form and function of the tissues of interest. When designing structures for engineering cartilage and osteochondral tissues, one must reconcile the need to develop a mechanically robust system that maintains the health of cells embedded in the scaffold. In this work, we present an approach that decouples the mechanical and biochemical needs and allows for the independent development of the structural and cellular niches in a scaffold.

Microscale Photopatterning of Through-thickness Modulus in a Monolithic and Functionally Graded 3D Printed Part.

3D printing is transforming traditional processing methods for applications ranging from tissue engineering to optics. To fulfill its maximum potential, 3D printing requires a robust technique for producing structures with precise three-dimensional (x, y and z) control of mechanical properties. Previous efforts to realize such spatial control of modulus within 3D printed parts have largely focused on low-resolution (mm to cm scale) multi-material processes and grayscale approaches that spatially vary the modulus in the x-y plane and energy dose-based ( = ) models that do not account for the resin's sub-linear response to irradiation intensity.