What is the Efficacy of Intra-Articular Platelet-Rich Plasma Injections for Knee Osteoarthritis in Clinical Practice? A "Real-Life" Prospective Cohort.

Introduction: Platelet-rich plasma (PRP) injections may improve symptoms in patients suffering from knee osteoarthritis. However, there is a lack of data on its effectiveness in a "real-life" cohort. This multi-site institutional registry study aimed to assess patients' longitudinal progress after PRP injection for knee osteoarthritis.

Tibial Bushing Wear at 28 Years of Follow-up After Rotating-Hinge Distal Femoral Replacement: A Case Report.

Case: A 58-year-old woman presented with swelling, stiffness, and pain of the right knee 28 years after rotating-hinge distal femoral replacement after osteosarcoma resection. She underwent revision. There was wear through the entire thickness of the polyethylene tibial sleeve bushing, and the implant was well-fixed.

Automated human induced pluripotent stem cell colony segmentation for use in cell culture automation applications.

Human induced pluripotent stem cells (hiPSCs) have demonstrated great promise for a variety of applications that include cell therapy and regenerative medicine. Production of clinical grade hiPSCs requires reproducible manufacturing methods with stringent quality-controls such as those provided by image-controlled robotic processing systems. In this paper we present an automated image analysis method for identifying and picking hiPSC colonies for clonal expansion using the CellX robotic cell processing system.

Cytocentric measurement for regenerative medicine.

Any Regenerative Medicine (RM) business requires reliably predictable cell and tissue products. Regulatory agencies expect control and documentation. However, laboratory tissue production is currently not predictable or well-controlled.

Automating iPSC generation to enable autologous photoreceptor cell replacement therapy.

Background: Inherited retinal degeneration is a leading cause of incurable vision loss in the developed world. While autologous iPSC mediated photoreceptor cell replacement is theoretically possible, the lack of commercially available technologies designed to enable high throughput parallel production of patient specific therapeutics has hindered clinical translation.

Methods: In this study, we describe the use of the Cell X precision robotic cell culture platform to enable parallel production of clinical grade patient specific iPSCs.

Regulatory and Ethical Aspects of Orthobiologic Therapies.

Orthobiologic therapies show significant promise to improve outcomes for patients with musculoskeletal pathology. There are considerable research efforts to develop strategies that seek to modulate the biological environment to promote tissue regeneration and healing and/or provide symptomatic relief. However, the regulatory pathways overseeing the clinical translation of these therapies are complex, with considerable worldwide variation.

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.

Should an Age Cutoff Be Considered for Elective Total Knee Arthroplasty Patients? An Analysis of Operative Success Based on Patient-Reported Outcomes.

Total knee arthroplasty (TKA) is increasing in the elderly population; however, some patients, family members, and surgeons raise age-related concerns over expected improvement and risks. This study aimed to (1) evaluate the relationship between age and change in patient-reported outcome measures (PROMs); (2) model how many patients would be denied improvements in PROMs if hypothetical age cutoffs were implemented; and (3) assess length of stay (LOS), readmission, reoperation, and mortality per age group. A prospective cohort of 4,396 primary TKAs (August 2015-August 2018) was analyzed.

Forward and reverse degradomics defines the proteolytic landscape of human knee osteoarthritic cartilage and the role of the serine protease HtrA1.

Objectives: Proteolytic destruction of articular cartilage, a major pathogenic mechanism in osteoarthritis (OA), was not previously investigated by terminomics strategies. We defined the degradome of human knee OA cartilage and the contribution therein of the protease HtrA1 using Terminal Amine Isotopic Labeling of Substrates (TAILS).

Design: Proteins from OA cartilage taken at knee arthroplasty (n = 6) or separately, from healthy cartilage incubated in triplicate with/without active HtrA1, were labeled at natural and proteolytically cleaved N-termini by reductive dimethylation, followed by trypsin digestion, enrichment of N-terminally labeled/blocked peptides, tandem mass spectrometry and positional peptide annotation to identify cleavage sites.

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.

Do patient-reported outcome measures improve after aseptic revision total hip arthroplasty?

Background: The purpose of this study was to determine patient-reported outcome measures (PROMs) changes in: (1) pain, function and global health; and (2) predictors of PROMs in patients undergoing aseptic revision total hip arthroplasty (rTHA) using a multilevel model with patients nested within surgeon.

Methods: A prospective cohort of 216 patients with baseline and 1-year PROMs who underwent aseptic rTHA between January 2016 and December 2017 were analysed. The most common indication for rTHA was aseptic loosening, instability, and implant failure.

Biologic Association Annual Summit: 2020 Report.

Interest and research in biologic approaches for tissue healing are exponentially growing for a variety of musculoskeletal conditions. The recent hype concerning musculoskeletal biological therapies (including viscosupplementation, platelet-rich plasma, and cellular therapies, or "stem cells") is driven by several factors, including demand by patients promising regenerative evidence supported by substantial basic and translational work, as well as commercial endeavors that complicate the scientific and lay understanding of biological therapy outcomes. While significant improvements have been made in the field, further basic and preclinical research and well-designed randomized clinical trials are needed to better elucidate the optimal indications, processing techniques, delivery, and outcome assessment.

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).

No clinically meaningful difference in 1-year patient-reported outcomes among major approaches for primary total hip arthroplasty.

Background: Debate continues around the most effective surgical approach for primary total hip arthroplasty (THA). This study's purpose was to compare 1-year patient-reported outcome measures (PROMs) of patients who underwent direct anterior (DA), transgluteal anterolateral (AL)/direct lateral (DL), and posterolateral (PL) approaches.

Methods: A prospective consecutive series of primary THA for osteoarthritis ( = 2390) were performed at 5 sites within a single institution with standardised care pathways (20 surgeons).

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.

The Potential Effects of Imposing a Body Mass Index Threshold on Patient-Reported Outcomes After Total Knee Arthroplasty.

Background: Operative eligibility thresholds based on body mass index (BMI) alone may risk restricting access to improved pain control, function, and quality of life. This study evaluated the use of BMI-cutoffs to offering TKA in avoiding: 1) 90-day readmission, 2) one-year mortality, and 3) failure to achieve clinically important one-year PROMS improvement (MCID).

Methods: A total of 4126 primary elective unilateral TKA patients from 2015 to 2018 were prospectively collected.

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.

The Cost-Effectiveness of Platelet-Rich Plasma Injections for Knee Osteoarthritis: A Markov Decision Analysis.

Background: Use of platelet-rich-plasma (PRP) injections for treating knee osteoarthritis has increased over the past decade. We used cost-effectiveness analysis to evaluate the value of PRP in delaying the need for total knee arthroplasty (TKA).

Methods: We developed a Markov model to analyze the baseline case: a 55-year-old patient with Kellgren-Lawrence grade-II or III knee osteoarthritis undergoing a series of 3 PRP injections with a 1-year delay to TKA versus a TKA from the outset.

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]).

Classification systems for platelet-rich plasma.

There is good scientific rationale to support the use of growth factors to promote musculoskeletal tissue regeneration. However, the clinical effectiveness of platelet-rich plasma (PRP) and other blood-derived products has yet to be proven. Characterization and reporting of PRP preparation protocols utilized in clinical trials for the treatment of musculoskeletal disease is highly inconsistent, and the majority of studies do not provide sufficient information to allow the protocols to be reproduced.