A Review of Recent Innovations in Cartilage Regeneration Strategies for the Treatment of Primary Osteoarthritis of the Knee: Intra-articular Injections.

Background: The pathology of primary osteoarthritis (OA) begins with structural cartilage damage, which initiates a self-propagating inflammatory pathway that further exacerbates cartilage deterioration. Current standard of care for knee primary OA involves treating the inflammatory symptoms to manage pain, which includes intra-articular (IA) injections of cortisone, an anti-inflammatory steroid, followed by a series of joint-cushioning hyaluronic acid gel injections. However, these injections do not delay the progression of primary OA. More focus on the underlying cellular pathology of OA has prompted researchers to develop treatments targeting the biochemical mechanisms of cartilage degradation. Purpose: Researchers have yet to develop a United States Food and Drug Administration (FDA)-approved injection that has been demonstrated to significantly regenerate damaged articular cartilage. This paper reviews the current research on experimental injections aimed at achieving cellular restoration of the hyaline cartilage tissue of the knee joint. Study Design: Narrative review. Methods: The authors conducted a narrative literature review examining studies on primary OA pathogenesis and a systematic review of non-FDA-approved IA injections for the treatment of primary OA of the knee, described as "disease-modifying osteoarthritis drugs" in phase 1, 2, and 3 clinical trials. Conclusion: New treatment approaches for primary OA investigate the potential of genetic therapies to restore native cartilage. It is clear that the most promising IA injections that could improve treatment of primary OA are bioengineered advanced-delivery steroid-hydrogel preparations, ex vivo expanded allogeneic stem cell injections, genetically engineered chondrocyte injections, recombinant fibroblast growth factor therapy, injections of selective proteinase inhibitors, senolytic therapy via injections, injectable antioxidant therapies, injections of Wnt pathway inhibitors, injections of nuclear factor-kappa ß inhibitors, injections of modified human angiopoietin-like-3, various potential viral vector-based genetic therapy approaches, and RNA genetic technology administered via injections.

Degraded RNA from Human Anterior Cruciate Ligaments Yields Valid Gene Expression Profiles.

Correlating gene expression patterns with biomechanical properties of connective tissues provides insights into the molecular processes underlying the tissue growth and repair. Cadaveric specimens such as human knees are widely considered suitable for biomechanical studies, but their usefulness for gene expression experiments is potentially limited by the unavoidable, nuclease-mediated degradation of RNA. Here, we tested whether valid gene expression profiles can be obtained using degraded RNA from human anterior cruciate ligaments (ACLs). Human ACL RNA (N = 6) degraded in vitro by limited ribonuclease digestion resemble highly degraded RNA isolated from cadaveric tissue. PCR threshold cycle (Ct) values for 90 transcripts (84 extracellular matrix, 6 housekeeping) in degraded RNAs variably ranged higher than values obtained from their corresponding non-degraded RNAs, reflecting both the expected loss of target templates in the degraded preparations as well as differences in the extent of degradation. Relative Ct values obtained for mRNAs in degraded preparations strongly correlated with the corresponding levels in non-degraded RNA, both for each ACL as well as for the pooled results from all six ACLs. Nuclease-mediated degradation produced similar, strongly correlated losses of housekeeping and non-housekeeping gene mRNAs. RNA degraded in situ yielded comparable results, confirming that in vitro digestion effectively modeled degradation by endogenous ribonucleases in frozen and thawed ACL. We conclude that, contrary to conventional wisdom, PCR-based expression analyses can yield valid mRNA profiles even from RNA preparations that are more than 90% degraded, such as those obtained from connective tissues subjected to biomechanical studies. Furthermore, legitimate quantitative comparisons between variably degraded tissues can be made by normalizing data to appropriate housekeeping transcripts.

Orthopaedic surgery residency match trends during COVID-19 pandemic: a cross-sectional study.

Orthopaedic surgery is one of the more competitive specialties for medical students to pursue. Students often complete subinternship rotations to demonstrate skill, work ethic, and fit within a program. Away rotations were suspended during the COVID-19 pandemic. Methods: This investigation compared home and regional match rates before the pandemic to the match cycle of 2020-2021. Results: There was a statistically significant increase in students matching to their home program, and insignificant increase in regional matches. Conclusions: This increase is likely due in part to the familiarity of students to programs where they could still rotate during the pandemic. Level of Evidence: Level IV.

Gender Differences in Seeking Health Care and Postintervention Pain Outcomes in Foot and Ankle Orthopedic Patients.

Background: A significant portion of the adults suffer from foot and ankle pain. The sex differences that exist throughout health care, pain management, and orthopedics may further complicate treatment strategies. The purpose of this study was to determine if there were any differences in women and men in health care seeking behavior and symptom chronicity in a West Texas orthopedic population with foot and ankle conditions. Materials and Methods: Data from 137 patients were collected in a retrospective chart review. Data were analyzed to determine if there were sex differences in time to primary care provider (PCP) after ankle injury, referral time from PCP to orthopedic surgeon consult, time from orthopedic consult to surgical intervention (if applicable), and chronicity of symptoms. Results: Women had a significantly higher percentage of chronic injuries than men (30.7% vs. 10.9%), but there were no sex differences in time to PCP from the time of injury, time from PCP visit to orthopedic consult, and time from orthopedic consult to surgical intervention. There were also no differences in those same time frames when compared by chronicity of symptoms (acute injury vs. chronic injury). Finally, we did not find any differences in pain scores between sexes or chronicity of symptoms. Conclusions: This study suggests that conventional health seeking sex differences may not apply to the foot and ankle patient population in West Texas and surrounding rural areas. Continuing to examine patterns in sex differences may lead to the development of more efficient and tailored treatment approaches and better outcomes.

Tai Chi Improves Brain Functional Connectivity and Plasma Lysophosphatidylcholines in Postmenopausal Women With Knee Osteoarthritis: An Exploratory Pilot Study.

Objective: A pre/post pilot study was designed to investigate neurobiological mechanisms and plasma metabolites in an 8-week Tai-Chi (TC) group intervention in subjects with knee osteoarthritis. Methods: Twelve postmenopausal women underwent Tai-Chi group exercise for 8 weeks (60 min/session, three times/week). Outcomes were measured before and after Tai Chi intervention including pain intensity (VAS), Brief Pain Inventory (BPI), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), plasma metabolites (amino acids and lipids), as well as resting-state functional magnetic resonance imaging (rs-fMRI, 10 min, eyes open), diffusion tensor imaging (DTI, 12 min), and structural MRI (4.5 min) in a subgroup. Clinical data was analyzed using paired t-tests; plasma metabolites were analyzed using Wilcoxon signed-rank tests; and rs-fMRI data were analyzed using seed-based correlations of the left and right amygdala in a two-level mixed-effects model (FSL software). Correlations between amygdala-medial prefrontal cortex (mPFC) connectivity and corresponding changes in clinical outcomes were examined. DTI connectivity of each amygdala was modeled using a Bayesian approach and probabilistic tractography. The associations between neurobiological effects and pain/physical function were examined. Results: Significant pre/post changes were observed with reduced knee pain (VAS with most pain: p = 0.018; WOMAC-pain: p = 0.021; BPI with worst level: p = 0.018) and stiffness (WOMAC-stiffness, p = 0.020), that likely contributed to improved physical function (WOMAC-physical function: p = 0.018) with TC. Moderate to large effect sizes pre/post increase in rs-fMRI connectivity were observed between bilateral mPFC and the amygdala seed regions (i.e., left: d = 0.988, p = 0.355; right: d = 0.600, p = 0.282). Increased DTI connectivity was observed between bilateral mPFC and left amygdala (d = 0.720, p = 0.156). There were moderate-high correlations (r = 0.28-0.60) between TC-associated pre-post changes in amygdala-mPFC functional connectivity and pain/physical function improvement. Significantly higher levels of lysophosphatidylcholines were observed after TC but lower levels of some essential amino acids. Amino acid levels (alanine, lysine, and methionine) were lower after 8 weeks of TC and many of the lipid metabolites were higher after TC. Further, plasma non-HDL cholesterol levels were lower after TC. Conclusion: This pilot study showed moderate to large effect sizes, suggesting an important role that cortico-amygdala interactions related to TC have on pain and physical function in subjects with knee osteoarthritis pain. Metabolite analyses revealed a metabolic shift of higher lyso-lipids and lower amino acids that might suggest greater fatty acid catabolism, protein turnover and changes in lipid redistribution in response to TC exercise. The results also support therapeutic strategies aimed at strengthening functional and structural connectivity between the mPFC and the amygdala. Controlled clinical trials are warranted to confirm these observed preliminary effects.

Triceps Tendon Rupture - A Novel Repair of an Uncommon Injury.

INTRODUCTION: Triceps tendon rupture is a rare injury accounting for <1% of all tendon injuries with varying repair techniques described. We present this novel repair to supplement available literature and help optimize the clinical outcomes for affected patients. We report this technique because it is unique in that we augmented our surgical fixation with a subtle variation in the described technique by repairing the deep portion of the triceps tendon as a separate step, maximizing the recreation of the anatomic footprint of the triceps. CASE REPORT: The patient is a 70-year-old Caucasian male presenting with pain, swelling, and ecchymosis around the elbow after the episode of injury. He also complained of a painful popping sensation whenever he ranged the elbow and an inability to extend, with pain and weakness any time he attempted elbow extension. Radiographs reviewed at his initial visit revealed a small osseous fragment approximately 5 cm proximal to the olecranon tip. Subsequent MR imaging confirmed our suspicion, showing a complete tear of the triceps tendon with hematoma at its insertion site and tendon retraction approximately 3 cm proximally. With the diagnosis of triceps tendon rupture conformed, we took the patient for primary tendon repair using suture with bone bridge and suture anchor, using elements from described techniques. Our technique was unique in that we performed repair of the deep and superficial triceps attachments as separate steps, in an endeavor to improve the anatomic reconstruction of the footprint and biomechanical strength. CONCLUSIONS: We combined findings from our review of the available literature with novel surgical techniques and suture design to maximize the patient outcome and minimize complications. The patient went on to have a very satisfactory functional recovery. We hope that this case report will complement the evidence-based care of these patients by orthopedic surgeons and lead to the best results possible.

Stem Cells for Treatment of Musculoskeletal Conditions - Orthopaedic/Sports Medicine Applications.

A myriad of musculoskeletal conditions afflicts a vast number of the world's population from birth to death. Countless pathological diseases and traumatic injuries (acute and chronic) contribute to different human disabilities, causing a tremendous financial toll on the economy of healthcare. The medical field is continually searching for novel ways to combat orthopedically related conditions. The immediate goal is the restoration of anatomy then ultimately return of function in hopes of enhancing quality if not the quantity of life. Traditional methods involve surgical correction/reconstruction of skeletal deformities from fractures/soft tissue damage/ruptures or replacement/resection of degenerated joints. Modern research is currently concentrating on innovative procedures to replenish/restore the human body close to its original/natural state [1, 2].

Recent Progress of Fabrication of Cell Scaffold by Electrospinning Technique for Articular Cartilage Tissue Engineering.

As a versatile nanofiber manufacturing technique, electrospinning has been widely employed for the fabrication of tissue engineering scaffolds. Since the structure of natural extracellular matrices varies substantially in different tissues, there has been growing awareness of the fact that the hierarchical 3D structure of scaffolds may affect intercellular interactions, material transportation, fluid flow, environmental stimulation, and so forth. Physical blending of the synthetic and natural polymers to form composite materials better mimics the composition and mechanical properties of natural tissues. Scaffolds with element gradient, such as growth factor gradient, have demonstrated good potentials to promote heterogeneous cell growth and differentiation. Compared to 2D scaffolds with limited thicknesses, 3D scaffolds have superior cell differentiation and development rate. The objective of this review paper is to review and discuss the recent trends of electrospinning strategies for cartilage tissue engineering, particularly the biomimetic, gradient, and 3D scaffolds, along with future prospects of potential clinical applications.

Effects of Tai Chi on gait kinematics, physical function, and pain in elderly with knee osteoarthritis--a pilot study.

Our previous study has demonstrated that 6 weeks of Tai Chi exercise significantly improves knee pain and stiffness in elderly with knee osteoarthritis. This study also examine the effects of Tai Chi exercise on gait kinematics, physical function, pain, and pain self-efficacy in elderly with knee osteoarthritis. In this prospective, pretest-posttest clinical trial, 40 men and women (64.4+/-8.3 years) diagnosed with knee osteoarthritis participated in 6 weeks of instructed Tai Chi training, 1 hour/session, 2 sessions/week. The following measures were taken at baseline and the conclusion of the intervention: (a) gait kinematics including stride length, stride frequency, and gait speed quantified using video analysis, (b) physical function, (c) knee pain, and (d) pain self-efficacy. Data were analyzed using repeated MANCOVA, MANOVA, ANOVA and Wilcoxon tests. After 6 weeks of Tai Chi exercise, stride length (p=0.023; 1.17+/-0.17 vs. 1.20+/-0.14 m), stride frequency (p=0.014; 0.91+/-0.08 vs. 0.93+/-0.08 strides/s), and consequently gait speed (p<0.025; 1.06+/-0.19 vs. 1.12+/-0.15 m/s) increased in the participants. Physical function was significantly improved (p<0.001) and knee pain was significantly decreased (p=0.002), while no change was observed in pain self-efficacy. In conclusion, these findings support that Tai Chi is beneficial for gait kinematics in elderly with knee osteoarthritis, and a longer term application is needed to substantiate the effect of Tai Chi as an alternative exercise in management of knee osteoarthritis.