Survivorship of the fixed-bearing medial unicompartmental knee arthroplasty: mean 14-year follow-up in a single medical center.

BACKGROUND: This study aimed to report the long-term survival of fixed-bearing medial unicompartmental knee arthroplasty (UKA) with a mean of 14-year follow-up, and to determine possible risk factors of failure. METHODS: We retrospectively evaluated 337 fixed-bearing medial UKAs implanted between 2003 and 2014. Demographic and radiographic parameters were measured, including pre-operative and post-operative anatomical femorotibial angle (aFTA), posterior tibial slope (PTS), and anatomical medial proximal tibial angle (aMPTA). Multivariate logistic regression analysis was applied to figure out risk factors. RESULTS: The mean follow-up time was 14.0 years. There were 32 failures categorized into implant loosening (n = 11), osteoarthritis progression (n = 7), insert wear (n = 7), infection (n = 4), and periprosthetic fracture (n = 3). Cumulative survival was 91.6% at 10 years and 90.0% at 15 years. No statistically significant parameters were found between the overall survival and failure groups. Age and hypertension were significant factors of implant loosening with odds ratio (OR) 0.909 (p = 0.02) and 0.179 (p = 0.04) respectively. In the insert wear group, post-operative aFTA and correction of PTS showed significance with OR 0.363 (p = 0.02) and 0.415 (p = 0.03) respectively. Post-operative aMPTA was a significant factor of periprosthetic fracture with OR 0.680 (p < 0.05). CONCLUSIONS: The fixed-bearing medial UKA provides successful long-term survivorship. Tibial component loosening is the major cause of failure. Older age and hypertension were factors with decreased risk of implant loosening.

Poly(methyl methacrylate) in Orthopedics: Strategies, Challenges, and Prospects in Bone Tissue Engineering.

Poly(methyl methacrylate) (PMMA) is widely used in orthopedic applications, including bone cement in total joint replacement surgery, bone fillers, and bone substitutes due to its affordability, biocompatibility, and processability. However, the bone regeneration efficiency of PMMA is limited because of its lack of bioactivity, poor osseointegration, and non-degradability. The use of bone cement also has disadvantages such as methyl methacrylate (MMA) release and high exothermic temperature during the polymerization of PMMA, which can cause thermal necrosis. To address these problems, various strategies have been adopted, such as surface modification techniques and the incorporation of various bioactive agents and biopolymers into PMMA. In this review, the physicochemical properties and synthesis methods of PMMA are discussed, with a special focus on the utilization of various PMMA composites in bone tissue engineering. Additionally, the challenges involved in incorporating PMMA into regenerative medicine are discussed with suitable research findings with the intention of providing insightful advice to support its successful clinical applications.

Enhancing wound healing and adhesion through dopamine-assisted gelatin-silica hybrid dressings.

Gelatin, widely employed in hydrogel dressings, faces limitations when used in high fluid environments, hindering effective material adhesion to wound sites and subsequently reducing treatment efficacy. The rapid degradation of conventional hydrogels often results in breakdown before complete wound healing. Thus, there is a pressing need for the development of durable adhesive wound dressings. In this study, 3-glycidoxypropyltrimethoxysilane (GPTMS) was utilized as a coupling agent to create gelatin-silica hybrid (G-H) dressings through the sol-gel method. The coupling reaction established covalent bonds between gelatin and silica networks, enhancing structural stability. Dopamine (DP) was introduced to this hybrid (G-H-D) dressing to further boost adhesiveness. The efficacy of the dressings for wound management was assessed through in-vitro and in-vivo tests, along with ex-vivo bioadhesion testing on pig skin. Tensile bioadhesion tests demonstrated that the G-H-D material exhibited approximately 2.5 times greater adhesion to soft tissue in wet conditions compared to pure gelatin. Moreover, in-vitro and in-vivo wound healing experiments revealed a significant increase in wound healing rates. Consequently, this material shows promise as a viable option for use as a moist wound dressing.

The role of EDIL3 in maintaining cartilage extracellular matrix and inhibiting osteoarthritis development.

Aims: Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown. Methods: We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators. Results: EDIL3 protein prevented chondrocyte clustering and maintained chondrocyte number and SOX9 expression in the human cartilage plug. Administration of EDIL3 protein prevented OA progression in STR/ort mice by maintaining the number of chondrocytes in the hyaline cartilage and the number of matrix-producing chondrocytes (MPCs). It reduced the degradation of aggrecan, the expression of matrix metalloproteinase (MMP)-13, the Osteoarthritis Research Society International (OARSI) score, and bone remodelling. It increased the porosity of the subchondral bone plate. Administration of an EDIL3 antibody increased the number of matrix-non-producing chondrocytes (MNCs) in cartilage and exacerbated the serum concentrations of OA-related pro-inflammatory cytokines, including monocyte chemotactic protein-3 (MCP-3), RANTES, interleukin (IL)-17A, IL-22, and GROα. Administration of ß1 and ß3 integrin agonists (CD98 protein) increased the expression of SOX9 in OA mice. Hence, EDIL3 might activate ß1 and ß3 integrins for chondroprotection. EDIL3 may also protect cartilage by attenuating the expression of IL-1ß-enhanced phosphokinase proteins in chondrocytes, especially glycogen synthase kinase 3 alpha/beta (GSK-3α/ß) and phospholipase C gamma 1 (PLC-γ1). Conclusion: EDIL3 has a role in maintaining the cartilage ECM and inhibiting the development of OA, making it a potential therapeutic drug for OA.

Topical Fibrin Sealant (Tisseel@) Does Not Provide a Synergic Blood-Conservation Effect with Tranexamic Acid in Total Knee Arthroplasty-A Prospective Randomized Controlled Trial.

Background and Objectives: The efficacy of tranexamic acid (TXA) in reducing perioperative blood loss during total knee arthroplasty (TKA) is well established. However, the potential synergistic blood-conservation effect of topical fibrin sealant (Tisseel@) remains unclear. This study aims to assess the effectiveness of the combination of Tisseel and TXA during TKA. Materials and Methods: A single-blinded, prospective, randomized controlled trial was conducted with 100 patients (100 knees) undergoing primary TKA. Participants were randomly assigned to either the TXA group (n = 50), receiving intravenous (IV) TXA, or the Tisseel@ + TXA group (n = 50), receiving intra-articular Tisseel@ combined with IV TXA. The primary outcomes included blood transfusion rate, decrease in Hb level, calculated blood loss, and estimated total postoperative blood loss. Secondary outcomes involved assessing clinical differences between the groups. Results: The transfusion rate was zero in both groups. The average estimated blood loss in the Tisseel@ + TXA group was 0.463 ± 0.2422 L, which was similar to that of the TXA group at 0.455 ± 0.2522 L. The total calculated blood loss in the Tisseel@ + TXA group was 0.259 ± 0.1 L, compared with the TXA group's 0.268 ± 0.108 L. The mean hemoglobin reduction in the first 24 h postoperatively was 1.57 ± 0.83 g/dL for the Tisseel@ + TXA group and 1.46 ± 0.82 g/dL for the TXA-only group. The reduction in blood loss in the topical Tisseel@ + TXA group was not significantly different from that achieved in the TXA-only group. The clinical results of TKA up to the 6-week follow-up were comparable between the groups. Conclusions: The combination of the topical fibrin sealant Tisseel@ and perioperative IV TXA administration, following the described protocol, demonstrated no significant synergistic blood-conservation effect in patients undergoing TKR.

Antimicrobial Peptide Conjugated on Graphene Oxide-Containing Sulfonated Polyetheretherketone Substrate for Effective Antibacterial Activities against Staphylococcus aureus.

In the present study, the antimicrobial peptide nisin was successfully conjugated onto the surface of sulfonated polyetheretherketone (SPEEK), which was decorated with graphene oxide (GO) to investigate its biofilm resistance and antibacterial properties. The PEEK was activated with sulfuric acid, resulting in a porous structure. The GO deposition fully covered the porous SPEEK specimen. The nisin conjugation was accomplished using the crosslinker 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) through a dip-coating method. The surface micrographs of the SPEEK-GO-nisin sample indicated that nisin formed discrete islets on the flat GO surface, allowing both the GO and nisin to perform a bactericidal effect. The developed materials were tested for bactericidal efficacy against Staphylococcus aureus (S. aureus). The SPEEK-GO-nisin sample had the highest antibacterial activity with an inhibition zone diameter of 27 mm, which was larger than those of the SPEEK-nisin (19 mm) and SPEEK-GO (10 mm) samples. Conversely, no inhibitory zone was observed for the PEEK and SPEEK samples. The surface micrographs of the bacteria-loaded SPEEK-GO-nisin sample demonstrated no bacterial adhesion and no biofilm formation. The SPEEK-nisin and SPEEK-GO samples showed some bacterial attachment, whereas the pure PEEK and SPEEK samples had abundant bacterial colonies and thick biofilm formation. These results confirmed the good biofilm resistance and antibacterial efficacy of the SPEEK-GO-nisin sample, which is promising for implantable orthopedic applications.

The Effect of Congruent Tibial Inserts in Total Knee Arthroplasty: A Network Meta-Analysis of Randomized Controlled Trials.

Objective: The aim of this study was to determine whether modern congruent tibial inserts are associated with superior outcomes in total knee arthroplasty (TKA). Background: Ultracongruent fixed-bearing (UCFB) and medial congruent fixed-bearing (MCFB) inserts have been known to be effective in total knee arthroplasty with patient satisfaction. Nonetheless, no supporting evidence to date exists to rank the clinical outcomes of these various congruent inserts in TKA compared with other important considerations in TKA including cruciate-retaining fixed-bearing (CRFB) and posterior-stabilized fixed-bearing (PSFB) inserts. Methods: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and Scopus up to 15 May 2022. We selected studies involving an active comparison of UCFB or MCFB in TKAs. We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs) and compared different congruent inserts. We ranked the clinical outcomes by SUCRA score with the estimate of the best treatment probability. Our primary outcomes were revision rates and radiolucent lines. Secondary outcomes were functional scores, including the range of motion (ROM), the Knee Society Score (KSS), the Oxford Knee Score (OKS), and WOMAC. Results: Eighteen RCTs with 1793 participants were analyzed. Our NMA ranked MCFB, CRFB, and UCFB with the lowest revision rates. CRFB and UCFB had the fewest radiolucent lines. UCFB had overall the best ROM. UCFB and MCFB had the best OKS score overall. Conclusions: The ranking probability for better clinical outcomes in congruent inserts demonstrated the superiority of congruent tibial inserts, including UCFB and MCFB. UCFB may be associated with better ROM and postoperative functional outcomes. However, integrating future RCTs for high-level evidence is necessary to confirm these findings.

Characterization and Advancement of an Evaluation Method for the Treatment of Spontaneous Osteoarthritis in STR/ort Mice: GRGDS Peptides as a Potential Treatment for Osteoarthritis.

STR/ort mice spontaneously exhibit the typical osteoarthritis (OA) phenotype. However, studies describing the relationship between cartilage histology, epiphyseal trabecular bone, and age are lacking. We aimed to evaluate the typical OA markers and quantify the subchondral bone trabecular parameters in STR/ort male mice at different weeks of age. We then developed an evaluation model for OA treatment. We graded the knee cartilage damage using the Osteoarthritis Research Society International (OARSI) score in STR/ort male mice with or without GRGDS treatment. We measured the levels of typical OA markers, including aggrecan fragments, matrix metallopeptidase-13 (MMP-13), collagen type X alpha 1 chain (COL10A1), and SRY-box transcription factor 9 (Sox9), and quantified epiphyseal trabecular parameters. Compared to the young age group, elderly mice showed an increased OARSI score, decreased chondrocyte columns of the growth plate, elevated expression of OA markers (aggrecan fragments, MMP13, and COL10A1), and decreased expression of Sox9 at the articular cartilage region in elderly STR/ort mice. Aging also significantly enhanced the subchondral bone remodeling and microstructure change in the tibial plateau. Moreover, GRGDS treatment mitigated these subchondral abnormalities. Our study presents suitable evaluation methods to characterize and measure the efficacy of cartilage damage treatments in STR/ort mice with spontaneous OA.

Clinical outcomes of various types of revision surgeries after unicompartmental knee arthroplasty failure.

PURPOSE: The advantages of unicompartmental knee arthroplasty (UKA) have led to the procedure being increasingly performed worldwide. However, revision surgery is required after UKA failure. According to the literature review, the choice of implant in revision surgery remains a debatable concern. This study analyzed the clinical results of different types of prostheses used in treating failed UKA. MATERIALS AND METHODS: This is a retrospective review of 33 failed medial UKAs between 2006 and 2017. Demographic data, failure reason, types of revision prostheses, and the severity of bone defects were analyzed. The patients were classified into three groups: primary prosthesis, primary prosthesis with a tibial stem, and revision prosthesis. The implant survival rate and medical cost of the procedures were compared. RESULTS: A total of 17 primary prostheses, 7 primary prostheses with tibial stems, and 9 revision prostheses were used. After a mean follow-up of 30.8 months, the survival outcomes of the three groups were 88.2%, 100%, and 88.9%, respectively (P = 0.640). The common bone defect in tibia site is Anderson Orthopedic Research Institute [AORI] grade 1 and 2a (16 versus 17). In patients with tibial bone defects AORI grade 2a, the failure rates of primary prostheses and primary prostheses with tibial stems were 25% and 0%, respectively. CONCLUSIONS: The most common cause for UKA failure was aseptic loosening. The adoption of a standardized surgical technique makes it easier to perform revision surgeries. Primary prostheses with tibial stems provided higher stability, leading to a lower failure rate due to less risk of aseptic loosening in patients with tibial AORI grade 2a. In our experience, we advise surgeons may try using primary prostheses in patients with tibial AORI grade 1 and primary prostheses with tibial stems in patients with tibial AORI grade 2a.

Randomized, double-blind, four-arm pilot study on the effects of chicken essence and type II collagen hydrolysate on joint, bone, and muscle functions.

BACKGROUND: Knee osteoarthritis (OA) is a leading cause of disability among older adults. Medical and surgical treatments are costly and associated with side effects. A natural nutraceutical, collagen hydrolysate, has received considerable attention due to its relieving effects on OA-associated symptoms. This study investigated the effects of hydrolyzed collagen type II (HC-II) and essence of chicken (BRAND'S Essence of Chicken) with added HC-II (EC-HC-II) on joint, muscle, and bone functions among older adults with OA. METHODS: Patients (n = 160) with grade 1-3 knee OA according to the Kellgren-Lawrence classification system, joint pain for ≥ 3 months, and a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of > 6 were randomly assigned with equal probability to consume EC-HC-II, HC-II, glucosamine HCl, or a placebo for 24 weeks in combination with resistance training. Outcome measurements were WOMAC score, visual analogue scale (VAS) pain score, grip strength, fat-free mass (FFM), and bone mass. RESULTS: All groups exhibited similar levels of improvement in WOMAC index scores after 24 weeks. HC-II significantly reduced VAS pain score by 0.9 ± 1.89 (p = 0.034) after 14 days. A repeated-measures analysis of variance showed that HC-II reduced pain levels more than the placebo did (mean ± standard error: - 1.3 ± 0.45, p = 0.021) after 14 days; the EC-HC-II group also had significantly higher FFM than the glucosamine HCl (p = 0.02) and placebo (p = 0.017) groups and significantly higher grip strength than the glucosamine HCl group (p = 0.002) at 24 weeks. CONCLUSION: HC-II reduces pain, and EC-HC-II may improve FFM and muscle strength. This suggests that EC-HC-II may be a novel holistic solution for mobility by improving joint, muscle, and bone health among older adults. Large-scale studies should be conducted to validate these findings. TRIAL REGISTRATION: This trial was retrospectively registered at ClinicalTrials.gov (NCT04483024).

Acetabular Revision Surgery with Tantalum Trabecular Metal Acetabular Cup for Failed Acetabular Cage Reconstruction with Bone Allografts: A Retrospective Study with Mid- to Long-Term Follow-Up.

Background: Acetabular cage reconstruction with bone allografts is among the successful strategies to deal with massive acetabular bone loss. However, the nonbiological fixation nature of cages can compromise long-term success. Tantalum trabecular metal acetabular cups (TM cups) have been used in acetabular revision surgery because of their increased initial stability and good bone ingrowth features. This study was performed to determine whether the bone stock of the acetabulum is enough to support a hemispheric TM cup after failed cage reconstruction with bone allografts. Methods: We retrospectively reviewed patients who received acetabular revision surgery with TM cups after failed cage reconstruction with bone allografts from 2006 to 2017. There were 12 patients (5 males and 7 females) included in this study, with a mean age of 61.5 years (38 to 81) at the time of re-revision surgery. The mean follow-up after re-revision surgery was 8.6 years (2.6 to 13.3). The endpoint was defined as the aseptic loosening of the TM cup and reoperation for any causes. The change in bone stock of the acetabulum between index revision and re-revision was assessed according to the Gross classification for acetabular bone loss. Results: One patient died after eight years of follow-up of a cause not related to hip surgery. Two patients received two-stage revision arthroplasty due to PJI after 3.2 and 9.4 years of follow-up, respectively. The bone stock of the acetabulum was significantly improved between index revision and re-revision surgery (p < 0.0001). The Kaplan−Meier survivorship was 100% with aseptic loosening as the endpoint and 90% and 75% at five- and ten-year follow-up, respectively, with reoperation for any reason as the endpoint. Even cage reconstruction with bone allografts will fail eventually, and the bone stock of the acetabulum will improve after union and incorporation between host bone and allografts. The restored bone stocks will facilitate further revision surgery with hemispheric TM cups. The biological fixation between host bone and tantalum trabecular metal can provide longstanding stability of the TM cup. Conclusions: The results of our study offer a viable option for patients with failed cage reconstruction with bone allografts.

Preparation of gamma poly-glutamic acid/hydroxyapatite/collagen composite as the 3D-printing scaffold for bone tissue engineering.

BACKGROUND: All types of movements involve the role of articular cartilage and bones. The presence of cartilage enables bones to move over one another smoothly. However, repetitive microtrauma and ischemia as well as genetic effects can cause an osteochondral lesion. Numerous treatment methods such as microfracture surgergy, autograft, and allograft, have been used, however, it possesses treatment challenges including prolonged recovery time after surgery and poses a financial burden on patients. Nowadays, various tissue engineering approaches have been developed to repair bone and osteochondral defects using biomaterial implants to induce the regeneration of stem cells.  METHODS: In this study, a collagen (Col)/γ-polyglutamate acid (PGA)/hydroxyapatite (HA) composite scaffold was fabricated using a 3D printing technique. A Col/γ-PGA/HA 2D membrane was also fabricated for comparison. The scaffolds (four layers) were designed with the size of 8 mm in diameter and 1.2 mm in thickness. The first layer was HA/γ-PGA and the second to fourth layers were Col/γ-PGA. In addition, a 2D membrane was constructed from hydroxyapatite/γ-PGA and collagen/γ-PGA with a ratio of 1:3. The biocompatibility property and degradation activity were investigated for both scaffold and membrane samples. Rat bone marrow mesenchymal stem cells (rBMSCs) and human adipose-derived stem cells (hADSCs) were cultured on the samples and were tested in-vitro to evaluate cell attachment, proliferation, and differentiation. In-vivo experiments were performed in the rat and nude mice models. RESULTS: In-vitro and in-vivo results show that the developed scaffold is of well biodegradation and biocompatible properties, and the Col-HA scaffold enhances the mechanical properties for osteochondrogenesis in both in-vitro and animal trials. CONCLUSIONS: The composite would be a great biomaterial application for bone and osteochondral regeneration.

Prismatic Silver Nanoparticles Decorated on Graphene Oxide Sheets for Superior Antibacterial Activity.

Spherical silver nanoparticles (Ag NPs) and silver nanoprisms (Ag NPrsms) were synthesized and decorated on graphene oxide (GO) nanosheets. The Ag contents were 29% and 23% in the GO−Ag NPs and GO−Ag NPrsms, respectively. The Ag NPrsms exhibited stronger (111) crystal signal than Ag NPs. The GO−Ag NPrsms exhibited higher Ag (I) content (75.6%) than GO-Ag NPs (69.9%). Increasing the nanomaterial concentration from 25 to 100 µg mL−1 improved the bactericidal efficiency, and the antibacterial potency was in the order: GO−Ag NPrsms > GO−Ag NPs > Ag NPrsms > Ag NPs > GO. Gram-positive Staphylococcus aureus (S. aureus) was more vulnerable than Gram-negative Escherichia coli (E. coli) upon exposure to these nanomaterials. The GO−Ag NPrsms demonstrated a complete (100%) bactericidal effect against S. aureus at a concentration of 100 µg mL−1. The GO−Ag composites outperformed those of Ag or GO due to the synergistic effect of bacteriostatic Ag particles and GO affinity toward bacteria. The levels of reactive oxygen species produced in the bacteria−nanomaterial mixtures were highly correlated to the antibacterial efficacy values. The GO−Ag NPrsms are promising as bactericidal agents to suppress biofilm formation and inhibit bacterial infection.

Do Serum C-Reactive Protein Trends Predict Treatment Outcome in Patients with Knee Periprosthetic Joint Infection Undergoing Two-Stage Exchange Arthroplasty?

Two-stage exchange arthroplasty is the standard treatment for knee periprosthetic joint infection (PJI). This study aimed to determine whether serial changes in C-reactive protein (CRP) values can predict the prognosis in patients with knee PJI. We retrospectively enrolled 101 patients with knee PJI treated with two-stage exchange arthroplasty at our institution from 2010 to 2016. We excluded patients with spacer complications and confounding factors affecting CRP levels. We tested the association between treatment outcomes and qualitative CRP patterns or quantitative CRP levels. Of the 101 patients, 24 (23.8%) had recurrent PJI and received surgical intervention after two-stage reimplantation. Patients with a fluctuating CRP pattern were more likely to receive antibiotics for a longer period (p < 0.001). There was greater risk of treatment failure if the CRP levels were higher when antibiotics were switched from an intravenous to oral form (p = 0.023). The patients who received antibiotics for longer than six weeks (p = 0.017) were at greater risk of treatment failure after two-stage arthroplasty. Although CRP patterns cannot predict treatment outcomes, CRP fluctuation in the interim period was associated with longer antibiotic duration, which was related to a higher treatment failure rate.

Application of structural allogenous bone graft in two-stage exchange arthroplasty for knee periprosthetic joint infection: a case control study.

BACKGROUND: Knee prosthetic joint infection (PJI) is a common but devastating complication after knee arthroplasty. The revision surgeries for knee PJI may become more challenging when it is associated with large bone defects. The application of structural bone allograft in knee revision surgeries with large bone defects is not a new technique. However, there is a lack of literature reporting its efficacy in PJI cases. This study aimed to investigate the outcome of structural fresh frozen allogenous bone grafts in treating patients in knee PJI with large bone defects. METHODS: We performed a retrospective cohort analysis of knee PJI cases treated with two-stage exchange arthroplasty at our institution from 2010 to 2016. 12 patients with structural allogenous bone graft reconstructions were identified as the study group. 24 patients without structural allograft reconstructions matched with the study group by age, gender, and Charlson comorbidity index were enrolled as the control group. The functional outcome of the study group was evaluated with the Knee Society Score (KSS). Treatment success was assessed according to the Delphi-based consensus definition. The infection relapse rate and implant survivorship were compared between groups. RESULTS: Revision knees with structural allograft presented excellent improvement in the KSS (33.1 to 75.4). There was no significant difference between infection relapse-free survival rate and prosthesis survival rate in the two groups. The 8-year prosthesis survival rate was 90.9% in the study group and 91% in the control group (p = 0.913). The 8-year infection relapse-free survival rate was 80 and 83.3% in the study group and control group, respectively (p = 0.377). CONCLUSION: The structural fresh frozen allogenous bone graft provided an effective way for bone defect reconstruction in knee PJI with an accountable survival rate. Meanwhile, using structural allografts did not increase the relapse rate of infection.

Revision Total Hip Arthroplasty with Primary Stem or Full-Porous-Coated Long Stem for Aseptic Femoral Component Loosening: A Matched-Pair Study.

BACKGROUND: Revision total hip arthroplasty (RTHA) for loosening the femoral stem is a technical challenge. Distally fixed, full-porous-coated long stems are widely accepted as the standard selection for these revisions. However, the success of primary stems in RTHA is not well known. METHODS: This study enrolled 24 patients with aseptic loosening of the femoral stem who underwent RTHA using primary stems. Another 72 patients with aseptic loosening who underwent RTHA using full-porous-coated long stems were matched in terms of operation date, proximal femoral bone stock (Paprosky classification), sex, and age. The primary and secondary outcomes of failure were the need for revision for any reason and the radiographic change in the stem respectively. RESULTS: In the primary stem group, one patient had a periprosthetic fracture and received a second RTHA 2 years after the previous one. The primary outcome's 5-and 10-year survival rates were both 95.8%. For the matched comparison group, one patient had an immediate periprosthetic fracture of the femoral shaft requiring further open reduction internal fixation surgery. Another patient had a full-porous-coated long stem breakage 6 years postoperatively, which required a second RTHA. The primary outcome's 5-and 10-year survival rates were 98.6% and 97.2%, respectively. CONCLUSION: Primary stems can achieve non-inferior clinical success compared to a full-porous-coated long stem for aseptic stem loosening RTHA in patients with adequate proximal femoral bone stock.

Treatment of knee osteoarthritis with intra-articular injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE®: a phase I/II, randomized, active-control, single-blind, multiple-center clinical trial.

OBJECTIVE: To evaluate the safety and efficacy of intra-articular (IA) injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE® for knee osteoarthritis. METHODS: This was a patient-blind, randomized, active-control trial consisted of 4 arms including hyaluronic acid (HA) control and 3 ELIXCYTE® doses. A total of 64 subjects were screened, and 57 subjects were randomized. The primary endpoints included the changes from baseline to post-treatment visit of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at Week 24 and the incidence of adverse events (AEs) and serious adverse events (SAEs). RESULTS: No ELIXCYTE®-related serious adverse events were reported during 96 weeks of follow-up and no suspected unexpected serious adverse reaction (SUSAR) or death was reported. The changes of the primary endpoint, WOMAC pain score at Week 24, showed significant differences in all ELIXCYTE® groups, as well as in HA groups between post-treatment visit and baseline. The ELIXCYTE® groups revealed significant decreases at Week 4 compared to HA group in WOMAC total scores, stiffness scores, functional limitation scores suggested the potential of ELIXCYTE® in earlier onset compared to those from HA. The significant differences of visual analog scale (VAS) pain score and Knee Society Clinical Rating System (KSCRS) functional activities score at Week 48 after ELIXCYTE® administration suggested the potential of ELIXCYTE® in the longer duration of the effectiveness compared to HA group. CONCLUSIONS: ELIXCYTE® for knee osteoarthritis treatment was effective, safe, and well-tolerated. The efficacy results were showed that ELIXCYTE® conferred the earlier onset of reductions in pain scores and improvements in functional scores than HA group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02784964. Registered 16 May, 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02784964.

The Risk Factor and Outcome of Metachronous Periprosthetic Joint Infections: A Retrospective Analysis With a Minimum Ten-Year Follow-Up.

BACKGROUND: Patients with multiple prosthetic joints are at risk of developing periprosthetic joint infections (PJIs). We aimed to determine whether PJI development at one site may lead to infection at another prosthetic joint site and assess the risk factors leading to this subsequent infection. METHODS: We reviewed all cases (294 patients with first-time PJI [159 hips, 135 knees]) with PJI treated at our institute between January 1994 and December 2020. The average follow-up period was 11.2 years (range 10.1-23.2). Patients were included if they had at least one other prosthetic joint at the time of developing a single PJI (96 patients). Patients with synchronous PJI were excluded from the study. The incidence of metachronous PJI was assessed, and the risk factors were determined by comparing different characteristics between patients without metachronous PJI. RESULTS: Of the 96 patients, 19.79% developed metachronous PJI. The identified causative pathogen was the same in 63.16% of the patients. The time to developing a second PJI was 789.84 days (range 10-3386). The identified risk factors were PJI with systemic inflammatory response syndrome, ≥3 stages of resection arthroplasty, and PJI caused by methicillin-resistant Staphylococcus aureus. CONCLUSION: PJI may predispose patients to subsequent PJI in another prosthesis with identified risks. Most causative organisms of metachronous PJI were the same species as those of the first PJI. We believe that bacteremia may be involved in pathogenesis, but further research is required.

Serum Insufficiency Induces RANKL-Independent Osteoclast Formation during Developing Ischemic ONFH.

Blood supply interruption induces hypoxia and reduces serum provision to cause ischemia-induced osteonecrosis, including avascular osteonecrosis of the femoral head (ONFH). Oxygen deficiency (hypoxia) is known to induce different expression patterns in osteoblasts and osteoclasts, which have been extensively studied. However, the effects of serum insufficiency in nutrients, growth factors, and hormones on osteoblast and osteoclast activity in the damaged area and nearby regions remain poorly understood. In this study, the expression of osteoblast and osteoclast marker proteins was elucidated through in vitro and ex vivo studies. The results indicate that serum insufficiency accelerates the formation of monocyte-derived osteoclasts. The combined effect of serum insufficiency and hypoxia (mimicking ischemia) suppressed the activity of alkaline phosphatase and calcification in osteoblasts after the stimulation of osteogenic growth factors. Serum insufficiency increased the activity of tartrate-resistant acid phosphatase, expression of phosphorylated extracellular signal-regulated kinases, and production of reactive oxygen species in monocyte-derived osteoclasts in the absence of receptor activator of nuclear factor kappa-Β ligand stimulation. The findings indicate that changes in the expression of osteoblast and osteoclast markers in necrotic bone extracts were similar to those observed during an in vitro study. These results also suggest that serum insufficiency may be involved in the regulation of osteoclast formation in patients with ONFH.

Ibudilast Mitigates Delayed Bone Healing Caused by Lipopolysaccharide by Altering Osteoblast and Osteoclast Activity.

Bacterial infection in orthopedic surgery is challenging because cell wall components released after bactericidal treatment can alter osteoblast and osteoclast activity and impair fracture stability. However, the precise effects and mechanisms whereby cell wall components impair bone healing are unclear. In this study, we characterized the effects of lipopolysaccharide (LPS) on bone healing and osteoclast and osteoblast activity in vitro and in vivo and evaluated the effects of ibudilast, an antagonist of toll-like receptor 4 (TLR4), on LPS-induced changes. In particular, micro-computed tomography was used to reconstruct femoral morphology and analyze callus bone content in a femoral defect mouse model. In the sham-treated group, significant bone bridge and cancellous bone formation were observed after surgery, however, LPS treatment delayed bone bridge and cancellous bone formation. LPS inhibited osteogenic factor-induced MC3T3-E1 cell differentiation, alkaline phosphatase (ALP) levels, calcium deposition, and osteopontin secretion and increased the activity of osteoclast-associated molecules, including cathepsin K and tartrate-resistant acid phosphatase in vitro. Finally, ibudilast blocked the LPS-induced inhibition of osteoblast activation and activation of osteoclast in vitro and attenuated LPS-induced delayed callus bone formation in vivo. Our results provide a basis for the development of a novel strategy for the treatment of bone infection.