Unraveling the complex interplay between abnormal hemorheology and shape asymmetry in flow through stenotic arteries.

Background And Objective: Stenosis or narrowing of arteries due to the buildup of plaque is a common occurrence in atherosclerosis and coronary artery disease (CAD), limiting blood flow to the heart and posing substantial cardiovascular risk. While the role of geometric irregularities in arterial stenosis is well-documented, the complex interplay between the abnormal hemorheology and asymmetric shape in flow characteristics remains unexplored.

Methods: This study investigates the influence of varying hematocrit (Hct) levels, often caused by conditions such as diabetes and anemia, on flow patterns in an idealized eccentric stenotic artery using computational fluid dynamics simulations.

Improved biological performance of human cartilage-derived progenitors in platelet lysate xenofree media in comparison to fetal bovine serum media.

Primary articular cartilage-derived cells are among the preferred contenders for cell-based therapy approaches for cartilage repair. Limited access to primary human cartilage tissue necessitates the process of in vitro cell expansion to obtain sufficient cells for therapeutic purposes. Therapeutic outcomes of such cell-based approaches become highly dependent on the quality of the in vitro culture-expanded cells.

Assessment of Clinical, Tissue, and Cell-Level Metrics Identify Four Biologically Distinct Knee Osteoarthritis Patient Phenotypes.

Objective: Clinical heterogeneity of primary osteoarthritis (OA) is a major challenge in understanding pathogenesis and development of targeted therapeutic strategies. This study aims to (1) identify OA patient subgroups phenotypes and (2) determine predictors of OA severity and cartilage-derived stem/progenitor concentration using clinical-, tissue-, and cell- level metrics.

Design: Cartilage, synovium (SYN) and infrapatellar fatpad (IPFP) were collected from 90 total knee arthroplasty patients.

A comprehensive dataset of histopathology images, grades and patient demographics for human Osteoarthritis Cartilage.

Osteoarthritis (OA) is a leading cause of disability in older adults and takes substantial toll at personal, economic and societal levels. There is inadequate comprehension of OA disease progression specifically during the early phases of OA. This knowledge is critical to understanding the heterogeneity in OA progression as well as enable development of targeted therapeutics at the start of the disease rather than end-stage.

Patient Age and Cell Concentration Influence Prevalence and Concentration of Progenitors in Bone Marrow Aspirates: An Analysis of 436 Patients.

Background: Connective tissue progenitors (CTPs) resident in native tissues serve as biological building blocks in tissue repair and remodeling processes. Methods for analysis and reporting on CTP quantity and quality are essential for defining optimal cell sources and donor characteristics and the impact of cell processing methods for cell therapy applications. The present study examines the influence of donor characteristics and cell concentration (nucleated cells/mL) on CTP prevalence (CTPs/million nucleated cells) and CTP concentration (CTPs/mL) in bone marrow aspirates (BMAs).

Characterization of heterogeneous primary human cartilage-derived cell population using non-invasive live-cell phase-contrast time-lapse imaging.

Reliable and reproducible cell therapy strategies to treat osteoarthritis demand an improved characterization of the cell and heterogeneous cell population resident in native cartilage tissue. Using live-cell phase-contrast time-lapse imaging (PC-TLI), this study investigates the morphological attributes and biological performance of the three primary biological objects enzymatically isolated from primary human cartilage: connective tissue progenitors (CTPs), non-progenitors (NPs) and multi-cellular structures (MCSs). The authors' results demonstrated that CTPs were smaller in size in comparison to NPs (P < 0.

Comparative Assessment of Primary Osteoarthritis Progression Using Conventional Histopathology, Polarized Light Microscopy, and Immunohistochemistry.

Objective: Evaluation of collagen orientation and arrangement in articular cartilage can improve our understanding of primary osteoarthritis (OA) progression and targeted therapies. Our goal was to determine if polarized light microscopy (PLM) for collagen organization is useful in identifying early primary OA features in comparison to current standard histopathological methods.

Design: Osteochondral specimens from 90 total knee arthroplasty patients with relatively preserved lateral femoral condyle were scored using (1) histological-histochemical grading system (HHGS); (2) Osteoarthritis Research Society International (OARSI); (3) PLM-Changoor system for repair cartilage, scores ranging between 0 (totally disorganized cartilage) and 5 (healthy adult cartilage); and (4) new PLM system for primary OA cartilage with superficial zone PLM (PLM-SZ) and deep zone PLM (PLM-DZ) scores, each ranging between 0 (healthy adult SZ and DZ collagen organization) and 4 (total loss of collagen organization).

Automated in-process characterization and selection of cell-clones for quality and efficient cell manufacturing.

Delivery of safe, effective and reliable cellular therapies, whether based on mesenchymal stromal cells (MSCs) or induced pluripotent stem cells (iPSCs), demand standardization of cell culture protocols. There is a need to develop automation platform that enables the users to generate culture expanded human cell populations that improves the quality and reduces batch-to-batch variation with respect to biological potential. Cell X™ robot was designed to address these current challenges in the cell fabrication industry.

Influence of Glucose Concentration on Colony-Forming Efficiency and Biological Performance of Primary Human Tissue-Derived Progenitor Cells.

Objective: Glucose concentrations used in current cell culture methods are a significant departure from physiological glucose levels. The study focuses on comparing the effects of glucose concentrations on primary human progenitors (connective tissue progenitors [CTPs]) used for cartilage repair.

Design: Cartilage- (Outerbridge grade 1, 2, 3; superficial and deep zone cartilage), infrapatellar fatpad-, synovium-, and periosteum-derived cells were obtained from 63 patients undergoing total knee arthroplasty and cultured simultaneously in fresh chondrogenic media containing 25 mM glucose (HGL) or 5 mM glucose (NGL) for pairwise comparison.

Native-Osteoarthritic Joint Resident Stem and Progenitor Cells for Cartilage Cell-Based Therapies: A Quantitative Comparison With Respect to Concentration and Biological Performance.

Background: Cell-based therapy for cartilage repair is a promising approach and is becoming an established technique. Yet, there is no consensus on the optimal cell source.

Purpose: To provide a donor-matched quantitative comparison of the connective tissue progenitors (CTPs) derived from cartilage (Outerbridge grade 1-3 [G1-2-3]), bone marrow aspirate concentrate (BMC), infrapatellar fat pad (IPFP), synovium, and periosteum with respect to (1) cell concentration ([Cell], cells/mL), (2) CTP prevalence (P, colonies per million cells), and (3) biological performance based on in vitro proliferation potential (cells per colony) colony density, and differentiation potential (expression of negatively charged extracellular matrix: glycosaminoglycan-rich extra cellular matrix [GAG-ECM]).

Reliable assessment of bone marrow and bone marrow concentrates using automated hematology analyzer.

A limiting factor in advancement of bone marrow based cell therapies is the lack of characterization of cell products delivered to patients. Using an automated hematology analyzer that can be implemented in clinical setting, the composition of bone marrow aspirates (n = 17 patients) and bone marrow concentrates (n = 12 patients) were assessed. ICC estimates were calculated for measuring reliability.

Donor-matched comparison of chondrogenic progenitors resident in human infrapatellar fat pad, synovium, and periosteum - implications for cartilage repair.

: There is a clinical need to better characterize tissue sources being used for stem cell therapies. This study focuses on comparison of cells and connective tissue progenitors (CTPs) derived from native human infrapatellar fatpad (IPFP), synovium (SYN), and periosteum (PERI). : IPFP, SYN, PERI were harvested from twenty-eight patients undergoing arthroplasty.

Primary Cells Isolated from Human Knee Cartilage Reveal Decreased Prevalence of Progenitor Cells but Comparable Biological Potential During Osteoarthritic Disease Progression.

Background: Current decisions on cellular therapies for osteoarthritis are based primarily on clinical experience or on assumptions about preferred cell sourcing. They have not been informed by rigorous standardized measurements of the chondrogenic connective-tissue progenitors (CTP-Cs) or their intrinsic diversity of chondrogenic potential. The goal of this study was to quantitatively define the CTP-Cs resident in cartilage of different grades of osteoarthritis and to compare their concentration, prevalence, and biological potential.

Variability in the Preparation, Reporting, and Use of Bone Marrow Aspirate Concentrate in Musculoskeletal Disorders: A Systematic Review of the Clinical Orthopaedic Literature.

Background: Interest in the therapeutic potential of bone marrow aspirate concentrate (BMAC) has grown exponentially. However, comparisons among studies and their processing methods are challenging because of inconsistent reporting of protocols, as well as poor characterization of the composition of the initial bone marrow aspirate and of the final products delivered. The purpose of this study was to perform a systematic review of the literature to evaluate the level of reporting related to the protocols used for BMAC preparation and the composition of BMAC utilized in the treatment of musculoskeletal diseases in published clinical studies.

Cellular Therapies in Orthopedics: Where Are We?

The orthopedic field has experienced several major practice-changing pivotal shifts in the past several decades, such as the invention and application of the arthroscope or the implementation and advancement of joint arthroplasties. Most of these previous breakthroughs have focused on surgical techniques and devices. However, the next major advance in the field is likely to be related to biologic treatments.

Progenitor cells from different zones of human cartilage and their correlation with histopathological osteoarthritis progression.

Cell-based therapies development for the treatment of osteoarthritis (OA) requires an understanding of the disease progression and attributes of the cells resident in cartilage. This study focused on quantitative assessment of the concentration and biological potential of stem and progenitor cells resident in different zones of cartilage displaying macroscopic Outerbridge grade 1-2 OA, and their correlation with OA progression based on established histologic scoring system. Lateral femoral condyles were collected from 15 patients with idiopathic OA and varus knees undergoing total knee arthroplasty.

Histopathological assessment of primary osteoarthritic knees in large patient cohort reveal the possibility of several potential patterns of osteoarthritis initiation.

Objective: The two main objectives of the study include (1) Test the hypothesis that the lateral femoral condyle (LFC) in patients with primary OA and varus knees undergoing total knee arthroplasty (TKA) can be used as a model to better characterize varying histological features of human OA, (2) Correlate characteristic OA features using the established histopathological scoring systems (HHGS and OARSI) to understand potential histopathological patterns of OA initiation.

Design: Two osteochondral specimens (4×4×8mm) were collected from fifty patient's LFC at the time of TKA (total 100 specimens), who presented preserved lateral knee compartment with joint space width>2mm. Three independent readers graded the sections on three different occasions using HHGS and OARSI systems.

High occurrence of osteoarthritic histopathological features unaccounted for by traditional scoring systems in lateral femoral condyles from total knee arthroplasty patients with varus alignment.

Background and purpose - A better understanding of the patterns and variation in initiation and progression of osteoarthritis (OA) in the knee may influence the design of therapies to prevent or slow disease progression. By studying cartilage from the human lateral femoral condyle (LFC), we aimed to: (1) assess specimen distribution into early, mild, moderate, and severe OA as per the established histopathological scoring systems (HHGS and OARSI); and (2) evaluate whether these 2 scoring systems provide sufficient tools for characterizing all the features and variation in patterns of OA. Patients and methods - 2 LFC osteochondral specimens (4 x 4 x 8 mm) were collected from 50 patients with idiopathic OA varus knee and radiographically preserved lateral compartment joint space undergoing total knee arthroplasty.

Effect of dual delivery of antibiotics (vancomycin and cefazolin) and BMP-7 from chitosan microparticles on Staphylococcus epidermidis and pre-osteoblasts in vitro.

The main aims of this manuscript are to: i) determine the effect of commonly used antibiotics to treat osteoarticular infections on osteoblast viability, ii) study the dual release of the growth factor (BMP-7) and antibiotics (vancomycin and cefazolin) from chitosan microparticles iii) demonstrate the bioactivity of the antibiotics released in vitro on Staphylococcus epidermidis. The novelty of this work is dual delivery of growth factor and antibiotic from the chitosan microparticles in a controlled manner without affecting their bioactivity. Cefazolin and vancomycin have different therapeutic concentrations for their action in vivo and therefore, two different concentrations of the drugs were used.

Bone regeneration using injectable BMP-7 loaded chitosan microparticles in rat femoral defect.

Injectable chitosan microparticles were prepared using a simple coacervation method under physiologically friendly conditions by eliminating oil or toxic chemical, and employing low temperature and pressure for growth factor stability. Amount of 200 ng of bone morphogenetic protein-7 (BMP-7) was incorporated in the chitosan microparticles by two methods: encapsulating and coating techniques. These microparticles were tested in vivo to determine the biological response in a rat femoral bone defect at 6 and 12 weeks.

IGF-1 release kinetics from chitosan microparticles fabricated using environmentally benign conditions.

The main objective of this study is to maximize growth factor encapsulation efficiency into microparticles. The novelty of this study is to maximize the encapsulated growth factors into microparticles by minimizing the use of organic solvents and using relatively low temperatures. The microparticles were fabricated using chitosan biopolymer as a base polymer and cross-linked with tripolyphosphate (TPP).

Injectable chitosan microparticles incorporating bone morphogenetic protein-7 for bone tissue regeneration.

This study investigates the influence of the controlled release of bone morphogenetic protein 7 (BMP-7) from cross-linked chitosan microparticles on pre-osteoblasts (OB-6) in vitro. BMP-7 was incorporated into microparticles by encapsulation during the particle preparation and coating after particle preparation. Chitosan microparticles had an average diameter of 700 µm containing ∼10-15 ng of BMP-7.

Examination of factors for use as potential predictors of human enteric pathogen survival in soil.

Aims: Three soils that varied in their physicochemical characteristics and microbial diversity were inoculated with Escherichia coli O157:H7 and Salmonella to determine the relative impact of abiotic and biotic factors on the pathogens' survival when the soil was held at 25°C.

Methods And Results: Three soils that were classified as having low, medium and high microbial diversity were divided into two batches for adjustment to 20% of water-holding capacity and to 40% of water-holding capacity. Soils were inoculated with both green fluorescent-labelled E.