Improved Postoperative Kneeling Ability in Posterior Stabilized Total Knee Arthroplasty with Medialised Dome-Patella Resurfacing: A Retrospective Comparative Outcome Analysis.

OBJECTIVES This investigation aimed to evaluate if the modifications to prosthesis designs improve patients' clinical and functional outcomes after total knee arthroplasty (TKA), with a special focus on pain and kneeling ability. METHODS Retrospective and comparative analysis of consecutive patients who were treated with posterior stabilized TKA using two different prostheses designs (single surgeon, single vendor). Group 1 received a traditional design TKA (PFC Sigma; DePuy, Inc., Warsaw, IN) with conventional dome-patella resurfacing and group 2 received a modern design implant (Attune; DePuy, Inc., Warsaw, IN), with medialised dome-patella resurfacing. Functional outcome (range of motion: ROM) and the Oxford Knee Score (OKS) were collected preoperatively, at 4-6 weeks and 12 months following surgery. RESULTS Ninety-nine participants were included. Of these, 30 received traditional design implants, and 69 the modern design knee implants. The comparison between the two implants showed a statistically significant increased total OKS and kneeling ability in the modern design cohort at 1-year follow-up compared to the traditional design cohort (p < 0.01). In the modern design group, 53% (N=37) could kneel easily or with little difficulty, compared to 30% (N=9) in the traditional design group. No statistically significant differences in ROM or the OKS pain component were seen. CONCLUSION The incorporation of a medialized dome-patella in modern knee implant design may offer advantages over traditional designs, as seen in improved total OKS and kneeling ability at one-year follow-up. Further research with larger cohorts is needed to confirm these findings and explore the broader impact of implant design changes on patient outcomes. LEVEL OF EVIDENCE Clinical Study, Level III

Audio-biofeedback versus the scale method for improving partial weight-bearing adherence in healthy older adults: a randomised trial.

PURPOSE To investigate how audio-biofeedback during the instruction of partial weight-bearing affected adherence, compared to traditional methods, in older adults; and to investigate the influence of individual characteristics. METHODS The primary outcome measure of this randomised controlled trial was the amount of load, measured as the ground reaction force, on the partial weight-bearing leg. The secondary outcome was the influence of individual characteristics on the amount of load. Included were healthy volunteers 60 years of age or older without gait impairment. Participants were randomly allocated to one of two groups; blinding was not possible. Partial weight-bearing of 20 kg was trained using crutches with audio-biofeedback (intervention group) or a bathroom scale (control group). The degree of weight-bearing was measured during six activities with sensor insoles. A mean load between 15 and 25 kg was defined as adherent. RESULTS There was no statistically significant difference in weight-bearing between the groups for all activities measured. For the sit-stand-sit activity, weight-bearing was within the adherence range of 15-25 kg (audio-biofeedback: 21.7 ± 16.6 kg; scale: 22.6 ± 13 kg). For standing, loading was below the lower threshold (10 ± 7 vs. 10 ± 10 kg). Weight-bearing was above the upper threshold for both groups for: walking (26 ± 11 vs. 34 ± 16), step-up (29 ± 18 vs. 34 ± 20 kg) and step-down (28 ± 15 vs. 35 ± 19 kg). Lower level of cognitive function, older age, and higher body mass index were correlated with overloading. CONCLUSION Audio-biofeedback delivered no statistically significant benefit over the scale method. Lower cognitive function, older age and higher body mass index were associated with overloading. TRIAL REGISTRATION Not applicable due not being a clinical trial and due to the cross-sectional design (one measurement point, no health intervention, no change in health of a person)

Spheroid-Like Cultures for Expanding Angiopoietin Receptor-1 (aka. Tie2) Positive Cells from the Human Intervertebral Disc.

Lower back pain is a leading cause of disability worldwide. The recovery of nucleus pulposus (NP) progenitor cells (NPPCs) from the intervertebral disc (IVD) holds high promise for future cell therapy. NPPCs are positive for the angiopoietin-1 receptor (Tie2) and possess stemness capacity. However, the limited Tie2+ NPC yield has been a challenge for their use in cell-based therapy for regenerative medicine. In this study, we attempted to expand NPPCs from the whole NP cell population by spheroid-formation assay. Flow cytometry was used to quantify the percentage of NPPCs with Tie2-antibody in human primary NP cells (NPCs). Cell proliferation was assessed using the population doublings level (PDL) measurement. Synthesis and presence of extracellular matrix (ECM) from NPC spheroids were confirmed by quantitative Polymerase Chain Reaction (qPCR), immunostaining, and microscopy. Compared with monolayer, the spheroid-formation assay enriched the percentage of Tie2+ in NPCs' population from ~10% to ~36%. Moreover, the spheroid-formation assay also inhibited the proliferation of the Tie2- NPCs with nearly no PDL. After one additional passage (P) using the spheroid-formation assay, NPC spheroids presented a Tie2+ percentage even further by ~10% in the NPC population. Our study concludes that the use of a spheroid culture system could be successfully applied to the culture and expansion of tissue-specific progenitors

Effect of different cryopreservation media on human nucleus pulposus cells' viability and trilineage potential

Introduction: Low back pain (LBP) is a significant cause of disability in many countries, affecting more than half a billion people worldwide. In the past, progenitor cells have been found within the nucleus pulposus (NP) of the human intervertebral disc (IVD). However, in the context of cell therapy, little is known about the effect of cryopreservation and expansion on here called “heterogenic” human NP cells (hNPCs), and whether commercially available cryopreservation media are more efficient than “commonly used” media in terms of cell viability. Materials: In this study, hNPCs from four trauma patients (age 40.5 ± 14.3 years) and two patients with degenerated IVDs (age 24 and 46 years), undergoing spinal surgery, were collected. To isolate hNPCs, the tissue was digested with a mild two-step protocol. After subsequent expansion, hNPCs at passages 2-5 were separated and either cryo-preserved for 1 week at −150°C or differentiated into osteogenic, adipogenic, or chondrogenic lineages for 21 days. Cryopreservation was performed with five different media to compare their effect on the cell's viability and differentiation potential. Cell viability was determined with flow cytometry using propidium iodide and the trilineage differentiation potential was assessed by quantitative polymerase chain reaction and histological analysis. Results: After 1 week of cryopreservation, the hNPC's cell viability was comparable for all conditions, that is, independent of the cryopreservation medium used (82.3 ± 0.8% of cell viability). Furthermore, hNPCs from trauma patients showed some evidence for adipogenic and chondrogenic differentiation and at lower levels, this and evidence of osteogenic differentiation could be confirmed with hNPCs from degenerated discs. Moreover, cryopreservation did not affect the cell's differentiation potential in the majority of the cases tested. Conclusion: “Commonly used” cryopreservation media seem to perform just as well as commercially available media in terms of cell viability and the overall maintenance of the hNPCs trilineage differentiation potential

Towards Tissue-Specific Stem Cell Therapy for the Intervertebral Disc: PPARδ Agonist Increases the Yield of Human Nucleus Pulposus Progenitor Cells in Expansion

(1) Background: Low back pain (LBP) is often associated with intervertebral disc degeneration (IVDD). Autochthonous progenitor cells isolated from the center, i.e., the nucleus pulposus, of the IVD (so-called nucleus pulposus progenitor cells (NPPCs)) could be a future cell source for therapy. The NPPCs were also identified to be positive for the angiopoietin-1 receptor (Tie2). Similar to hematopoietic stem cells, Tie2 might be involved in peroxisome proliferator-activated receptor delta (PPARδ) agonist-induced self-renewal regulation. The purpose of this study was to investigate whether a PPARδ agonist (GW501516) increases the Tie2+ NPPCs’ yield within the heterogeneous nucleus pulposus cell (NPC) population. (2) Methods: Primary NPCs were treated with 10 µM of GW501516 for eight days. Mitochondrial mass was determined by microscopy, using mitotracker red dye, and the relative gene expression was quantified by qPCR, using extracellular matrix and mitophagy-related genes. (3) The NPC’s group treated with the PPARδ agonist showed a significant increase of the Tie2+ NPCs yield from ~7% in passage 1 to ~50% in passage two, compared to the NPCs vehicle-treated group. Furthermore, no significant differences were found among treatment and control, using qPCR and mitotracker deep red. (4) Conclusion: PPARδ agonist could help to increase the Tie2+ NPCs yield during NPC expansion

Assessing lower extremity loading during activities of daily living using continuous-scale physical functional performance 10 and wireless sensor insoles: a comparative study between younger and older adults.

PURPOSE This study aims to investigate the lower extremity loading during activities of daily living (ADLs) using the Continuous Scale of Physical Functional Performance (CS-PFP 10) test and wireless sensor insoles in healthy volunteers. METHODS In this study, 42 participants were recruited, consisting of 21 healthy older adults (mean age 69.6 ± 4.6 years) and 21 younger healthy adults (mean age 23.6 ± 1.8 years). The performance of the subjects during ADLs was assessed using the CS-PFP 10 test, which comprised 10 tasks. The lower extremity loading was measured using wireless sensor insoles (OpenGo, Moticon, Munich, Germany) during the CS-PFP 10 test, which enabled the measurement of ground reaction forces, including the mean and maximum total forces during the stance phase, expressed in units of body weight (BW). RESULTS The total CS-PFP 10 score was significantly lower in older participants compared to the younger group (mean total score of 57.1 ± 9.0 compared to 78.2 ± 5.4, respectively). No significant differences in the mean total forces were found between older and young participants. The highest maximum total forces were observed during the tasks 'endurance walk' (young: 1.97 ± 0.34 BW, old: 1.70 ± 0.43 BW) and 'climbing stairs' (young: 1.65 ± 0.36 BW, old: 1.52 ± 0.28 BW). Only in the endurance walk, older participants showed a significantly higher maximum total force (p < 0.001). CONCLUSION The use of wireless sensor insoles in a laboratory setting can effectively measure the load on the lower extremities during ADLs. These findings could offer valuable insights for developing tailored recommendations for patients with partial weight-bearing restrictions

Gender authorship trends in spine research publications - Research across different countries from 1976 to 2020.

•Gender trends in authorship showed an increase in female authors from 1976 to 2020.•In 2020, Europe had the highest and Asia the lowest proportion of female authors.•The Netherlands had the highest proportion of women and Japan the lowest

Influence of Angiopoietin Treatment with Hypoxia and Normoxia on Human Intervertebral Disc Progenitor Cell’s Proliferation, Metabolic Activity, and Phenotype

Increasing evidence implicates intervertebral disc (IVD) degeneration as a major contributor to low back pain. In addition to a series of pathogenic processes, degenerated IVDs become vascularized in contrast to healthy IVDs. In this context, angiopoietin (Ang) plays a crucial role and is involved in cytokine recruitment, and anabolic and catabolic reactions within the extracellular matrix (ECM). Over the last decade, a progenitor cell population has been described in the nucleus pulposus (NP) of the IVD to be positive for the Tie2 marker (also known as Ang-1 receptor). In this study, we investigated the influence of Ang-1 and Ang-2 on human NP cell (Tie2+, Tie2- or mixed) populations isolated from trauma patients during 7 days in normoxia (21% O2) or hypoxia (≤ 5% O2). At the end of the process, the proliferation and metabolic activity of the NP cells were analyzed. Additionally, the relative gene expression of NP-related markers was evaluated. NP cells showed a higher proliferation depending on the Ang treatment. Moreover, the study revealed higher NP cell metabolism when cultured in hypoxia. Additionally, the relative gene expression followed, with an increase linked to the oxygen level and Ang concentration. Our study comparing different NP cell populations may be the start of new approaches for the treatment of IVD degeneration

Effect of glucose depletion and fructose administration during chondrogenic commitment in human bone marrow-derived stem cells.

BACKGROUND Bone marrow mesenchymal stromal cells (BMSCs) are promising for therapeutic use in cartilage repair, because of their capacity to differentiate into chondrocytes. Often, in vitro differentiation protocols employ the use of high amount of glucose, which does not reflect cartilage physiology. For this reason, we investigated how different concentrations of glucose can affect the chondrogenic differentiation of BMSCs in cell culture pellets. Additionally, we investigated how fructose could influence the chondrogenic differentiation in vitro. METHODS BMSC were isolated from six donors and cultured in DMEM containing glucose at either 25 mM (HG), 5.5 mM (LG) or 1 mM (LLG), and 1% non-essential amino acids, 1% ITS+, in the presence of 100 nM dexamethasone, 50 µg/ml ascorbic acid-2 phosphate and 10 ng/ml TGF-β1. To investigate the effect of different metabolic substrates, other groups were exposed to additional 25 mM fructose. The media were replaced every second day until day 21 when all the pellets were harvested for further analyses. Biochemical analysis for glycosaminoglycans into pellets and released in medium was performed using the DMMB method. Expression of GLUT3 and GLUT5 was assayed by qPCR and validated using FACS analysis and immunofluorescence in monolayer cultures. Chondrogenic differentiation was further confirmed by qPCR analysis of COL2A1, COL1A1, COL10A1, ACAN, RUNX2, SOX9, SP7, MMP13, and PPARG, normalized on RPLP0. Type 2 collagen expression was subsequently validated by immunofluorescence analysis. RESULTS We show for the first time the presence of fructose transporter GLUT5 in BMSC and its regulation during chondrogenic commitment. Additionally, decreasing glucose concentration during chondrogenesis dramatically decreased the yield of differentiation. However, the use of fructose alone or together with low glucose concentrations does not limit cell differentiation, but on the contrary it might help in maintaining a stable chondrogenic phenotype comparable with the standard culture conditions (high glucose). CONCLUSION This study provides evidence that BMSC express GLUT5 and differentially regulate GLUT3 in the presence of glucose variation. This study gives a better comprehension of BMSCs sugar use during chondrogenesis