Regulatory Considerations of Orthobiologic Procedures

The injection of biologic products for musculoskeletal pathologies is an emerging and promising field; however, dubious and unsafe uses for these products are often marketed. The Food and Drug Administration (FDA) has determined the need for varying degrees of regulation for these products for safety and efficacy. These regulations are frequently updated and federally enforced. As the regulatory landscape changes, clinicians using biologic products must stay informed to remain within the purview of the FDA. This article describes the current regulations of the most common products: platelet-rich plasma, bone marrow aspirate concentrate, adipose-derived products, and birth tissue products

MOF@Cell : 3D printed biobased filters anchored with a green metal–organic framework for effluent treatment

Multifunctional, biobased materials processed by means of additive manufacturing technology can behighly applicable within the water treatment industry. This work summarizes a scalable and sustainablemethod of anchoring a green metal–organic framework (MOF) SU-101 onto the surface of 3D printed,biobased matrices built of polylactic acid (PLA)-based composites reinforced with TEMPO-oxidizedcellulose nanofibers (TCNFs). The two tested anchoring methods were hydrolysis via either concentratedhydrochloric acid treatment or via a photooxidation reaction using UV–ozone treatment. Stabledeposition of SU-101 distributed homogenously over the filter surface was achieved and confirmed byFT-IR, XPS and SEM measurements. The obtained 3D printed and functionalized MOF@PLA andMOF@TCNF/PLA (aka MOF@Cell) filters exhibit high efficiency in removing heavy metal ions from mineeffluent and methylene blue from contaminated water, as demonstrated through batch adsorptionexperiments. In addition to their potential for removal of contaminants from water, the MOF@Cell filtersalso exhibit excellent mechanical properties with a Young's modulus value of about 1200 MPa,demonstrating their potential for use in practical water treatment applications. The MOF@Cell filterswere able to maintain their structural integrity and filtration performance even after multiple cycles ofuse and regeneration. This study highlights the potential of multifunctional, biobased materials processedby additive manufacturing technology as a cost-effective alternative to traditional water treatmentmethods. The MOF@Cell filters presented in this study demonstrate high efficiency, durability, andreusability, making them promising candidates for practical applications in the modern water treatmentindustry

Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial.

Various types of cellular injection have become a popular and costly treatment option for patients with knee osteoarthritis despite a paucity of literature establishing relative efficacy to each other or corticosteroid injections. Here we aimed to identify the safety and efficacy of cell injections from autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction and allogeneic human umbilical cord tissue-derived mesenchymal stromal cells, in comparison to corticosteroid injection (CSI). The study was a phase 2/3, four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients with a diagnosis of knee osteoarthritis (Kellgren-Lawrence II-IV). Participants were randomized to the three different arms with a 3:1 distribution. Arm 1: autologous bone marrow aspirate concentrate (n = 120), CSI (n = 40); arm 2: umbilical cord tissue-derived mesenchymal stromal cells (n = 120), CSI (n = 40); arm 3: stromal vascular fraction (n = 120), CSI (n = 40). The co-primary endpoints were the visual analog scale pain score and Knee injury and Osteoarthritis Outcome Score pain score at 12 months versus baseline. Analyses of our primary endpoints, with 440 patients, revealed that at 1 year post injection, none of the three orthobiologic injections was superior to another, or to the CSI control. In addition, none of the four groups showed a significant change in magnetic resonance imaging osteoarthritis score compared to baseline. No procedure-related serious adverse events were reported during the study period. In summary, this study shows that at 1 year post injection, there was no superior orthobiologic as compared to CSI for knee osteoarthritis. ClinicalTrials.gov Identifier: NCT03818737

Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes.

Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response