CCL2/CCR2 Signalling in Mesenchymal Stem/Progenitor Cell Recruitment and Fracture Healing in Mice.

Macrophage efferocytosis (clearance of apoptotic cells) is crucial for tissue homeostasis and wound repair, where macrophages secrete factors that promote resolution of inflammation and regenerative signalling. This study examined the role of efferocytic macrophage-associated CCL2 secretion, its influence on mesenchymal stem/progenitor cell (MSPC) chemotaxis, and in vivo cell recruitment using Ccr2 (KO) mice with disrupted CCL2 receptor signalling in two regenerative models: ossicle implants and ulnar stress fractures. Single cell RNA sequencing and PCR validation indicated that efferocytosis of various apoptotic cells at bone injury sites (osteoblasts, pre-osteoblasts, MSPC) upregulated CCL2.

Matrix Architecture and Mechanics Regulate Myofibril Organization, Costamere Assembly, and Contractility in Engineered Myocardial Microtissues.

The mechanical function of the myocardium is defined by cardiomyocyte contractility and the biomechanics of the extracellular matrix (ECM). Understanding this relationship remains an important unmet challenge due to limitations in existing approaches for engineering myocardial tissue. Here, they established arrays of cardiac microtissues with tunable mechanics and architecture by integrating ECM-mimetic synthetic, fiber matrices, and induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), enabling real-time contractility readouts, in-depth structural assessment, and tissue-specific computational modeling.

Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels.

Hydrogels can improve the delivery of mesenchymal stromal cells (MSCs) by providing crucial biophysical cues that mimic the extracellular matrix. The differentiation of MSCs is dependent on biophysical cues like stiffness and viscoelasticity, yet conventional hydrogels cannot be dynamically altered after fabrication and implantation to actively direct differentiation. We developed a composite hydrogel, consisting of type I collagen and phase-shift emulsion, where osteogenic differentiation of MSCs can be non-invasively modulated using ultrasound.

Augmentation of Tendon and Ligament Repair with Fiber-Reinforced Hydrogel Composites.

This review highlights the promise of fiber-reinforced hydrogel composites (FRHCs) for augmenting tendon and ligament repair and regeneration. Composed of reinforcing fibers embedded in a hydrogel, these scaffolds provide both mechanical strength and a conducive microenvironment for biological processes required for connective tissue regeneration. Typical properties of FRHCs are discussed, highlighting their ability to simultaneously fulfill essential mechanical and biological design criteria for a regenerative scaffold.

Controlling chaos using edge computing hardware.

Machine learning provides a data-driven approach for creating a digital twin of a system - a digital model used to predict the system behavior. Having an accurate digital twin can drive many applications, such as controlling autonomous systems. Often, the size, weight, and power consumption of the digital twin or related controller must be minimized, ideally realized on embedded computing hardware that can operate without a cloud-computing connection.

Engineered Microenvironmental Cues from Fiber-Reinforced Hydrogel Composites Drive Tenogenesis and Aligned Collagen Deposition.

Effective tendon regeneration following injury is contingent on appropriate differentiation of recruited cells and deposition of mature, aligned, collagenous extracellular matrix that can withstand the extreme mechanical demands placed on the tissue. As such, myriad biomaterial approaches have been explored to provide biochemical and physical cues that encourage tenogenesis and template aligned matrix deposition in lieu of dysfunctional scar tissue formation. Fiber-reinforced hydrogels present an ideal biomaterial system toward this end given their transdermal injectability, tunable stiffness over a range amenable to tenogenic differentiation of progenitors, and capacity for modular inclusion of biochemical cues.

Controlling chaotic maps using next-generation reservoir computing.

In this work, we combine nonlinear system control techniques with next-generation reservoir computing, a best-in-class machine learning approach for predicting the behavior of dynamical systems. We demonstrate the performance of the controller in a series of control tasks for the chaotic Hénon map, including controlling the system between unstable fixed points, stabilizing the system to higher order periodic orbits, and to an arbitrary desired state. We show that our controller succeeds in these tasks, requires only ten data points for training, can control the system to a desired trajectory in a single iteration, and is robust to noise and modeling error.

Early Outcomes Following Plantar Condylectomy and Imbrication of Plantar Plate to Metatarsal Neck for Metatarsalgia and Grade 0 Lesser Toe Metatarsophalangeal Joint Instability.

Background: Metatarsalgia and plantar plate tears are characterized by forefoot pain and toe deformity in severe cases. Conservative management may slow progression of symptoms; however, definitive treatment often requires operative intervention. The purpose of this observational study was to evaluate the combination of plantar condylectomy and surgical imbrication of the plantar plate to the metatarsal neck to repair grade 0 plantar plate injuries.

Building-Block Size Mediates Microporous Annealed Particle Hydrogel Tube Microenvironment Following Spinal Cord Injury.

Spinal cord injury (SCI) is a life-altering event, which often results in loss of sensory and motor function below the level of trauma. Biomaterial therapies have been widely investigated in SCI to promote directional regeneration but are often limited by their pre-constructed size and shape. Herein, the design parameters of microporous annealed particles (MAPs) are investigated with tubular geometries that conform to the injury and direct axons across the defect to support functional recovery.

Degree of Tendon Retraction and Younger Age Are Associated With Functional Decline Following Nonoperative Management of Complete Proximal Hamstring Ruptures.

Purpose: To characterize functional outcomes of patients with complete proximal hamstring tendon ruptures who were treated nonoperatively and determine whether there are patient characteristics associated with unfavorable outcomes.

Methods: We retrospectively identified patients aged 18-80 (treated 1/2000-12/2019) who received nonoperative management of complete rupture of the hamstring tendon origin. Participants completed the Lower Extremity Functional Scale (LEFS), as well as Tegner Activity Scale (TAS), and a chart review was conducted to obtain demographic and medical information.

Discoidin domain receptor 2 regulates aberrant mesenchymal lineage cell fate and matrix organization.

Extracellular matrix (ECM) interactions regulate both the cell transcriptome and proteome, thereby determining cell fate. Traumatic heterotopic ossification (HO) is a disorder characterized by aberrant mesenchymal lineage (MLin) cell differentiation, forming bone within soft tissues of the musculoskeletal system following traumatic injury. Recent work has shown that HO is influenced by ECM-MLin cell receptor signaling, but how ECM binding affects cellular outcomes remains unclear.

Physical and Soluble Cues Enhance Tendon Progenitor Cell Invasion into Injectable Synthetic Hydrogels.

Synthetic hydrogels represent an exciting avenue in the field of regenerative biomaterials given their injectability, orthogonally tunable mechanical properties, and potential for modular inclusion of cellular cues. Separately, recent advances in soluble factor release technology have facilitated control over the soluble milieu in cell microenvironments via tunable microparticles. A composite hydrogel incorporating both of these components can robustly mediate tendon healing following a single injection.

Anterior cruciate ligament graft forces are sensitive to fixation angle and tunnel position within the native femoral footprint during passive flexion.

Background: Anterior cruciate ligament (ACL) graft position within the anatomic femoral footprint of the native ACL and the flexion angle at which the graft is fixed (i.e., fixation angle) are important considerations in ACL reconstruction surgery.

Direct comparison of angiogenesis in natural and synthetic biomaterials reveals that matrix porosity regulates endothelial cell invasion speed and sprout diameter.

Vascularization of large, diffusion-hindered biomaterial implants requires an understanding of how extracellular matrix (ECM) properties regulate angiogenesis. Sundry biomaterials assessed across many disparate angiogenesis assays have highlighted ECM determinants that influence this complex multicellular process. However, the abundance of material platforms, each with unique parameters to model endothelial cell (EC) sprouting presents additional challenges of interpretation and comparison between studies.

Implementation of a Coronavirus Disease 2019 Vaccination Condition of Employment in a Community Nursing Home.

The rate of coronavirus disease 2019 (COVID-19) vaccination uptake by US nursing home staff remains low despite the increased risks of viral transmission and related morbidity and mortality in this setting. This study describes vaccine uptake activities including a COVID-19 vaccination condition of employment (COE) policy in one community nursing home. This case study summarizes the timeline of vaccination uptake activities, staff vaccination rates over time, and stakeholder perspectives around the implementation of a COVID-19 vaccination COE.

Entrapment of Hydrophilic and Hydrophobic Molecules in Beads Prepared from Isolated Denatured Whey Protein.

The oral route of administration is by far the most convenient route, especially in the treatment of chronic conditions. However, many therapeutics present formulation difficulties which make them unsuitable for oral delivery. Recently, we synthesized a denatured whey protein isolate (dWPI) bead entrapped with insulin.

Magnetic Alignment of Electrospun Fiber Segments Within a Hydrogel Composite Guides Cell Spreading and Migration Phenotype Switching.

Fibrous extracellular matrix (ECM) proteins provide mechanical structure and adhesive scaffolding to resident cells within stromal tissues. Aligned ECM fibers play an important role in directing morphogenetic processes, supporting mechanical loads, and facilitating cell migration. Various methods have been developed to align matrix fibers in purified biopolymer hydrogels, such as type I collagen, including flow-induced alignment, uniaxial tensile deformation, and magnetic particles.

Synthesis and In Vivo Evaluation of Insulin-Loaded Whey Beads as an Oral Peptide Delivery System.

For many diabetics, daily, lifelong insulin injections are required to effectively manage blood glucose levels and the complications associated with the disease. This can be a burden and reduces patient quality of life. Our goal was to develop a more convenient oral delivery system that may be suitable for insulin and other peptides.

Status and trends of orthophosphate concentrations in groundwater used for public supply in California.

Phosphorus is a necessary nutrient for all organisms. However excessive phosphorus can cause eutrophication in surface water. Groundwater can be an important nonpoint contributor of phosphorus to surface water bodies.

Author Correction: Recombinant Incretin-Secreting Microbe Improves Metabolic Dysfunction in High-Fat Diet Fed Rodents.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Engagement of the Secondary Ligamentous and Meniscal Restraints Relative to the Anterior Cruciate Ligament Predicts Anterior Knee Laxity.

Background: Patients with high-grade preoperative side-to-side differences in anterior laxity as assessed via the Lachman test after unilateral anterior cruciate ligament (ACL) rupture are at heightened risk of early ACL graft failure. Biomechanical factors that predict preoperative side-to-side differences in anterior laxity are poorly understood.

Purpose: To assess, in a cadaveric model, whether the increase in anterior laxity caused by sectioning the ACL (a surrogate for preoperative side-to-side differences in anterior laxity) during a simulated Lachman test is associated with two biomechanical factors: (1) the tibial translation at which the secondary anterior stabilizers, including the remaining ligaments and the menisci, begin to carry force, or , relative to that of the ACL or (2) the forces carried by the ACL and secondary stabilizers at the peak applied anterior load.

Tibiofemoral Kinematics During Compressive Loading of the ACL-Intact and ACL-Sectioned Knee: Roles of Tibial Slope, Medial Eminence Volume, and Anterior Laxity.

Background: Tibial geometry and knee laxity have been identified as risk factors for both noncontact anterior cruciate ligament (ACL) rupture and instability in the setting of ACL insufficiency via clinical studies; yet, their biomechanical relationships with tibiofemoral kinematics during compressive loading are less well understood. The purpose of this study was to identify the relative contributions of sagittal tibial slope, medial tibial eminence volume, and anterior knee laxity to tibiofemoral kinematics with axial compression in both ACL-intact and ACL-sectioned cadaveric knees.

Methods: Computed tomography (CT) data were collected from 13 human cadaveric knees (mean donor age, 45 ± 11 years; 8 male).

Effect of Macronutrient Type and Gastrointestinal Release Site on PYY Response in Normal Healthy Subjects.

Background And Aims: Enteroendocrine L cells release satiety inducing hormones in response to stimulation by luminal macronutrients. We sought to profile the differential effect of macronutrient type and site of release on circulating concentrations of the L cell-derived enteroendocrine hormone peptide tyrosine tyrosine (amino acids 1 to 36) (PYY).

Materials And Methods: Eight healthy volunteers were recruited to a randomized, double-blinded, six-way crossover study.

Automated, accurate, and three-dimensional method for calculating sagittal slope of the tibial plateau.

Increased posterior-inferior directed slope of the subchondral bone of the lateral tibial plateau is a risk factor for noncontact rupture of the anterior cruciate ligament (ACL). Previous measures of lateral tibial slope, however, vary from study to study and often lack documentation of their accuracy. These factors impede identifying the magnitude of lateral tibial slope that increases risk of noncontact ACL rupture.

Anterior laxity, lateral tibial slope, and in situ ACL force differentiate knees exhibiting distinct patterns of motion during a pivoting event: A human cadaveric study.

Knee instability following anterior cruciate ligament (ACL) rupture compromises function and increases risk of injury to the cartilage and menisci. To understand the biomechanical function of the ACL, previous studies have primarily reported the net change in tibial position in response to multiplanar torques, which generate knee instability. In contrast, we retrospectively analyzed a cohort of 13 consecutively tested cadaveric knees and found distinct motion patterns, defined as the motion of the tibia as it translates and rotates from its unloaded, initial position to its loaded, final position.