Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes – the main cellular components in BMAC – interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes. Cite this article:
Bone marrow stem cells (BMSCs) represent a collection of different cell types exhibiting stem cell characteristics but with notable heterogeneity. Among these, Skeletal Stem Cells (SSCs) represent a distinct matrix subgroup within BMSC and demonstrate a specialized capacity to facilitate bone formation, recruit chondrocytes, and contribute to hematopoiesis. SSCs play a pivotal role in orchestrating the functions of skeletal organs. Local ischemia has a significant impact on cell survival and function. We hypothesize that bone ischemia induces alterations in the differentiation potential of SSCs, consequently influencing changes in bone structure. We mechanically dissected tissue from the necrotic segment in the femoral head and more normal appearing areas from the femoral neck of specimens from 5 patients diagnosed with osteonecrosis of the femoral head (ONFH). These tissues were enzymatically broken down into individual cell suspensions. Utilizing fluorescence-activated cell sorting (FACS) based on specific surface markers indicative of human skeletal stem cells (hSSC), namely CD45- CD235a- CD31- TIE2- Podoplanin (PDPN)+ CD146- CD73+ CD164+, we isolated a distinct cell population. Subsequent in vitro evaluations, focusing on clonogenicity, osteogenesis, and chondrogenesis were conducted to assess the functional prowess of these SSCs. Moreover, we introduced BMP2 at a concentration of 50ng/ml to SSCs extracted from necrotic regions to potentially reinstate their osteogenic capabilities. We effectively isolated SSCs from both Necrotic and Non-necrotic Zones. We observed an augmented clonal formation capacity and chondrogenesis ability of SSCs isolated from the necrotic region, accompanied by a significant decline in osteogenic ability ( Ischemia adversely affects the proliferation and function of SSCs, resulting in a diminished osteogenic capacity and an insensitivity to BMP2, ultimately leading to structural alterations in bone tissue.
Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice. We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR).Aims
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Instability is a common indication for revision total hip arthroplasty (THA). However, even after the initial revision, some patients continue to have recurrent dislocations. This study investigates those at risk for recurrent dislocation after revision THA for instability at a single institution. Between 2009 and 2019, 163 patients underwent revision THA for instability at a single institution. Thirty-three of these patients required re-revision THA due to recurrent dislocation. Cox proportional hazard models with death as a competing event were used to analyze risk factors, including prosthesis sizing and alignment. Paired t-tests or Wilcoxon signed rank tests were used to assess patient outcomes (Veterans RAND 12 (VR-12) physical score, VR-12 mental score, Harris Hip Score, and hip disability and osteoarthritis outcome score for joint replacement). Duration of follow-up until either re-revision or final follow-up was a mean of 45.3 ± 38.2 months. The 1-year cumulative incidence for recurrent dislocation after revision was 8.7%, which increased to 19.6% at 5 years and 32.9% at 10 years postoperatively. In the multivariable analysis, high ASA score [HR 2.71], being underweight (BMI<18 kg/m2) [HR 36.26] or overweight/obese (BMI>25 kg/m2) [HR 4.31], use of specialized liners [HR 5.51–10.71], lumbopelvic stiffness [HR 6.29], and postoperative abductor weakness [HR 7.20] were significant risk factors for recurrent dislocation. Increasing the cup size decreased the dislocation risk [HR 0.89]. The dual mobility construct did not affect the risk for recurrent dislocation in univariate or multivariable analyses. VR-12 physical and HHS (pain and function) scores improved postoperatively at midterm. Patients requiring revision THA for instability are at risk for recurrent dislocation. Higher ASA scores, abnormal BMI, use of special liners, lumbopelvic stiffness, and postoperative abductor weakness are significant risk factors for re-dislocation.
In early stage osteonecrosis of the femoral head (ONFH), core decompression (CD) is often performed; however, approximately 30% of CD cases progress to femoral head collapse. Bone healing can be augmented by preconditioning MSCs (pMSCs) with inflammatory cytokines. Another immunomodulatory approach is the timely resolution of inflammation using cytokines such as IL-4. We investigated the efficacy of pMSC and genetically modified MSCs that over-express IL-4 (IL4-MSCs) on steroid-associated ONFH in rabbits. Thirty-six male skeletally mature NZW rabbits received methylprednisolone acetate (20mg/kg) IM once 4 weeks before surgery. There were 6 groups:
CD alone – a 3 mm drill hole
hydrogel (HG) - 200 μl of hydrogel carrier MSCs–1 million rabbit MSCs pMSC - LPS (20 μg/ml) + TNFα (20 ng/ml) preconditioned MSCs IL4-MSCs – rabbit IL-4 over-expressing MSCs IL4-pMSCs – preconditioned IL-4 over-expressing MSCs Eight weeks after surgery, femurs were harvested, and evaluated by microCT, biomechanical, and histological analyses.Introduction
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Secondary osteonecrosis of the knee (SOK) generally occurs in relatively young patients in their working years; at advanced stages of SOK, the only viable surgical option is total knee arthroplasty (TKA). We conducted a retrospective study to investigate implant survivorship, clinical and radiographic outcomes, and complications of cemented TKA with/without patellar resurfacing for SOK. Thirty-eight cemented TKAs in 27 patients with non-traumatic SOK with a mean age 43 years (range 17–65) were retrospectively reviewed. Twenty-one patients (78%) were female. Mean body mass index was 31 kg/m2 (range 20–48); 11 patients (41%) received bilateral TKAs. Twenty patients (74%) had a history of corticosteroid use and 18% had a history of alcohol abuse. Patellar osteonecrosis was coincidentally found in six knees (16%), all of which had no anterior knee pain and had no patellofemoral joint collapse. The mean follow-up was 7 years (range 2–12). Knee Society Score (KSS) and radiographic outcomes were evaluated at 6 weeks, 1 year, then every 2–3 years thereafter.Background
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Surgical treatment for osteonecrosis of the femoral head (ONFH) includes both joint-preserving techniques and joint replacement. Joint preservation is more effective in early-stage ONFH; thus, prompt diagnosis when the femoral head is still salvageable is an important clinical goal. We report a 20-year retrospective study that summarizes the proportion of patients diagnosed with early-stage versus late-stage ONFH at initial presentation to our practice. Our institutional database was reviewed to identify patients 18–65 years of age who were diagnosed with atraumatic ONFH in our clinic between 1998–2018. The Association Research Circulation Osseous (ARCO) system was used to stage ONFH, based on available imaging. Patients with prior surgical treatment for ONFH were excluded.Background
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Up to 10% of fractures result in undesirable outcomes, for which female sex is a risk factor. Cellular sex differences have been implicated in these different healing processes. Better understanding of the mechanisms underlying bone healing and sex differences in this process is key to improved clinical outcomes. This study utilized a macrophage–mesenchymal stem cell (MSC) coculture system to determine: 1) the precise timing of proinflammatory (M1) to anti-inflammatory (M2) macrophage transition for optimal bone formation; and 2) how such immunomodulation was affected by male A primary murine macrophage-MSC coculture system was used to demonstrate the optimal transition time from M1 to M2 (polarized from M1 with interleukin (IL)-4) macrophages to maximize matrix mineralization in male and female MSCs. Outcome variables included Alizarin Red staining, alkaline phosphatase (ALP) activity, and osteocalcin protein secretion.Objectives
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Intra-articular injections of local anaesthetics (LA), glucocorticoids (GC), or hyaluronic acid (HA) are used to treat osteoarthritis (OA). Contrast agents (CA) are needed to prove successful intra-articular injection or aspiration, or to visualize articular structures dynamically during fluoroscopy. Tranexamic acid (TA) is used to control haemostasis and prevent excessive intra-articular bleeding. Despite their common usage, little is known about the cytotoxicity of common drugs injected into joints. Thus, the aim of our study was to investigate the effects of LA, GC, HA, CA, and TA on the viability of primary human chondrocytes and tenocytes Human chondrocytes and tenocytes were cultured in a medium with three different drug dilutions (1:2; 1:10; 1:100). The following drugs were used to investigate cytotoxicity: lidocaine hydrochloride 1%; bupivacaine 0.5%; triamcinolone acetonide; dexamethasone 21-palmitate; TA; iodine contrast media; HA; and distilled water. Normal saline served as a control. After an incubation period of 24 hours, cell numbers and morphology were assessed.Objectives
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Patients may present with concurrent symptomatic hip and spine problems, with surgical treatment indicated for both. Controversy exists over which procedure, total hip arthroplasty (THA) or lumbar spine procedure, should be performed first, and does the surgeon's area of expertise influence the choice. Clinical scenarios were devised for 5 fictional patients with both symptomatic hip and lumbar spine disorders for which surgical treatment was indicated. An email with survey link was sent to 110 clinical members of the Hip Society and 101 experienced spine surgeons in the USA requesting responses to: which procedure should be performed first, and the rationale for the decision with comments. The clinical scenarios were painful hip osteoarthritis and (1) lumbar spinal stenosis with neurologic claudication; (2) lumbar degenerative spondylolisthesis with leg pain; (3) lumbar disc herniation with leg weakness; (4) lumbar scoliosis with back pain; and (5) thoracolumbar disc herniation with myelopathy. Surgeon choices were compared among scenarios and between surgical specialties using chi-square analysis and comments analyzed using text mining.Purpose
Materials & Methods
Patients with rheumatoid arthritis (RA) have a higher risk of surgical site infection (PJI) than patients with osteoarthritis (OA). Disease modifying therapy is in widespread use in RA patients, and biologic medications may increase Staphylococcus aureus colonization rates. Because S. aureus colonization likely increases risk of surgical infection, perioperative assessments and therapies to decrease the risk of invasive S.aureus infections may be warranted. The objective of this study was to determine if there was a difference in S. aureus carriage among patients with RA, OA, and RA on biologics (RA+B). An a priori power analysis determined 123 participants per group were needed to detect a relative difference of 20% among groups with 80% power. After IRB approval, patients were screened; included patients met American College of Rheumatology classification criteria. Patients were approached between April 2017 and May 2018 and asked to perform a nasal swab while on site using the Center for Disease Control's swabbing protocol; questionnaires pertaining to their current health status were collected. Swabs were inoculated onto ChromAgar/ChromID MRSA plates for detection of S. aureus. Mann-Whitney U and Chi-square tests were used to evaluate baseline differences between groups. Logistic regression evaluated the associations between groups and S. aureus carriage. All statistical analyses were performed using SAS Software version 9.3 (SAS Institute, Cary, NC); statistical significance was defined as p<0.05.Introduction
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