Gender Differences in Pain, Function, and Quality of Life Five Years Following Primary Total Knee Arthroplasty.

BACKGROUND: Multiple authors have sought to determine what patient characteristics influence outcomes after total knee arthroplasty (TKA). The impact of gender on outcomes after TKA remains controversial. Previous studies had less than 5 years of follow-up after TKA. The aim of this evaluation was to determine what differences in pain, function, and quality of life (QoL) exist between female and male patients 5 years after primary TKA. METHODS: A prospective, multicenter cohort of 11,602 unilateral primary TKA patients (7,284 females and 4,318 males) was prospectively evaluated. All patients were enrolled in the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement. Demographic data, musculoskeletal and medical comorbid conditions, and patient-reported outcome measures, including the Knee Injury and Osteoarthritis Outcome (KOOS) and Short-Form (36-item) Health Survey mental component score (MCS) and physical component score (PCS) were collected preoperatively and at 5 years after TKA. Descriptive statistics were generated, and stratified by gender, and differences in pain, function, and QoL between female and male patients were evaluated. Multivariate regression models with a 95% confidence interval (CI) were used to assess the role of patient gender as a predictive factor for KOOS pain and function in daily living (ADL) scores reported 5 years after primary TKA, while adjusting for other variables. RESULTS: Prior to surgery, female patients reported worse pain (KOOS pain 46 versus 52), function (KOOS ADL 53 versus 59), and QoL (KOOS QoL 26 versus 29) than male patients. The differences in preoperative scores ranged from 2.70 (KOOS QoL) to 6.12 (KOOS ADL). At 5 years after TKA, female patients reported slightly worse pain (87 versus 89), function (85 versus 87), and QoL (74 versus 75) when compared to male patients. The differences in the mean 5-year postoperative KOOS scores (range, 0.99 to 2.73), although statistically significant (P < .001), were clinically negligible. Female patients achieved greater improvement in pain (41 versus 37), function (32 versus 29), and QoL (48 versus 46) scores in comparison to male patients. Female patients also reported lower preoperative PCS global function (33 versus 35) scores, 5-year postoperative PCS scores (45 versus 46), and MCS global mental function scores (52 versus 54). Similarly, the differences in the 5-year postoperative Short-Form (36-item) Health Survey MCS and PCS scores were clinically negligible. Multivariate regression analysis showed that female gender was not independently predictive for either pain (ß = -1.08; 95% CI [-1.25 to 1.03] [P = .85]) or function (ß = 0.64; 95% CI [-0.51 to 1.79] [P = .28]) 5 years after surgery. CONCLUSIONS: There are no clinically significant gender differences in pain, function, or QoL 5 years after TKA. Female patients typically have worse symptoms prior to surgery, improve more than male patients, and end up with pain, function, and QoL scores clinically equal to male patients. These data can enhance the shared decision-making process between female patients and surgeons and assist in setting appropriate patient expectations prior to TKA.

Predictive Factors of Pain and Functional Outcome 5 Years Following Total Hip Arthroplasty: A Prospective Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement Cohort Study.

BACKGROUND: Previous reports have identified a number of potential predictors of pain and function after total hip arthroplasty (THA). However, the results of these studies were conflicting, and most had a short follow-up after THA. The purpose of this study was to identify factors predictive of pain and function 5 years after THA. METHODS: A multicenter cohort of 7,934 primary unilateral THA patients was prospectively enrolled in the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement consortium. Demographic data, comorbidities, and patient-reported outcome measures were collected preoperatively and postoperatively at 5 years, including the Hip Disability and OSteoarthritis Outcome Score (HOOS) pain and activities of daily living (ADL) scores. Multivariate logistic regression models with 95% confidence interval were used to identify independent predictors of pain and function at 5 years. RESULTS: The patient dissatisfaction percentage was 8.2% at 5 years after THA. The multivariate regression identified the following predictive factors for the HOOS pain score at 5 years: age, educational level, insurance, smoking, race, Charlson Comorbidity Index, back pain severity, number of other lower extremity painful joints, the Knee Injury and Osteoarthritis Outcome Score pain severity of the ipsilateral knee, preoperative Short-Form Health Survey 36-item (SF-36) mental component summary score, and HOOS pain scores. The multivariate regression identified the following predictor factors for HOOS ADL score at 5 years: body mass index, insurance, smoking, race, back pain severity, number of other lower extremity painful joints, Knee Injury and Osteoarthritis Outcome Score pain severity of ipsilateral knee, preop HOOS ADL, and preoperative SF-36 mental component summary score and SF-36 physical component summary score. CONCLUSIONS: Overall, 8.2% of patients were dissatisfied 5 years after primary THA. We have identified a number of factors that predict less improvement in pain and function 5 years after THA. These potentially modifiable factors can be targeted with preoperative patient optimization programs to improve patient outcomes and satisfaction after primary THA. Knowledge of these factors that predict less improvement in pain and function can assist the surgeon and patient during shared decision-making, and in setting appropriate patient expectations preoperatively.

Strengthening Quality Measurement to Predict Success for Total Knee Arthroplasty: Results from a Nationally Representative Total Knee Arthroplasty Cohort.

BACKGROUND: When performed well on appropriate patients, total knee arthroplasty (TKA) can dramatically improve quality of life. Patient-reported outcome measures (PROMs) are increasingly used to measure outcome following TKA. Accurate prediction of improvement in PROMs after TKA potentially plays an important role in judging the surgical quality of the health-care institutions as well as informing preoperative shared decision-making. Starting in 2027, the U.S. Centers for Medicare & Medicaid Services (CMS) will begin mandating PROM reporting to assess the quality of TKAs. METHODS: Using data from a national cohort of patients undergoing primary unilateral TKA, we developed an original model that closely followed a CMS-proposed measure to predict success, defined as achieving substantial clinical benefit, specifically at least a 20-point improvement on the Knee injury and Osteoarthritis Outcome Score, Joint Arthroplasty (KOOS, JR) at 1 year, and an enhanced model with just 1 additional predictor: the baseline KOOS, JR. We evaluated each model's performance using the area under the receiver operator characteristic curve (AUC) and the ratio of observed to expected (model-predicted) outcomes (O:E ratio). RESULTS: We studied 5,958 patients with a mean age of 67 years; 63% were women, 93% were White, and 87% were overweight or obese. Adding the baseline KOOS, JR improved the AUC from 0.58 to 0.73. Ninety-four percent of those in the top decile of predicted probability of success under the enhanced model achieved success, compared with 34% in its bottom decile. Analogous numbers for the original model were less discriminating: 77% compared with 57%. Only the enhanced model predicted success accurately across the spectrum of baseline scores. The findings were virtually identical when we replicated these analyses on only patients ≥65 years of age. CONCLUSIONS: Adding a baseline knee-specific PROM score to a quality measurement model in a nationally representative cohort dramatically improved its predictive power, eliminating ceiling and floor effects and mispredictions for readily identifiable patient subgroups. The enhanced model neither favors nor discourages care for those with greater knee dysfunction and requires no new data collection. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Modulating On-Demand Release of Vancomycin from Implant Coatings via Chemical Modification of a Micrococcal Nuclease-Sensitive Oligonucleotide Linker.

Periprosthetic infections are one of the most serious complications in orthopedic surgeries, and those caused by Staphylococcus aureus (S. aureus) are particularly hard to treat due to their tendency to form biofilms on implants and their notorious ability to invade the surrounding bones. The existing prophylactic local antibiotic deliveries involve excessive drug loading doses that could risk the development of drug resistance strains. Utilizing an oligonucleotide linker sensitive to micrococcal nuclease (MN) cleavage, we previously developed an implant coating capable of releasing covalently tethered vancomycin, triggered by S. aureus-secreted MN, to prevent periprosthetic infections in the mouse intramedullary (IM) canal. To further engineer this exciting platform to meet broader clinical needs, here, we chemically modified the oligonucleotide linker by a combination of 2'-O-methylation and phosphorothioate modification to achieve additional modulation of its stability/sensitivity to MN and the kinetics of MN-triggered on-demand release. We found that when all phosphodiester bonds within the oligonucleotide linker 5'-carboxy-mCmGTTmCmG-3-acrydite, except for the one between TT, were replaced by phosphorothioate, the oligonucleotide (6PS) stability significantly increased and enabled the most sustained release of tethered vancomycin from the coating. By contrast, when only the peripheral phosphodiester bonds at the 5'- and 3'-ends were replaced by phosphorothioate, the resulting oligonucleotide (2PS) linker was cleaved by MN more rapidly than that without any PS modifications (0PS). Using a rat femoral canal periprosthetic infection model where 1000 CFU S. aureus was inoculated at the time of IM pin insertion, we showed that the prophylactic implant coating containing either 0PS- or 2PS-modified oligonucleotide linker effectively eradicated the bacteria by enabling the rapid on-demand release of vancomycin. No bacteria were detected from the explanted pins, and no signs of cortical bone changes were detected in these treatment groups throughout the 3 month follow-ups. With an antibiotic tethering dose significantly lower than conventional antibiotic-bearing bone cements, these coatings also exhibited excellent biocompatibility. These chemically modified oligonucleotides could help tailor prophylactic anti-infective coating strategies to meet a range of clinical challenges where the risks for S. aureus prosthetic infections range from transient to long-lasting.

Age-Related Differences in Pain, Function, and Quality of Life Following Primary Total Knee Arthroplasty: Results From a FORCE-TJR (Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement) Cohort.

BACKGROUND: The impact of age on patient outcomes after total knee arthroplasty (TKA) remains controversial. Age has shown no effect on outcome in some studies, while others have reported better or worse outcome in younger patients. The aims of this study were to determine the differences in pain, function, and quality of life (QoL) reported 1 year after TKA across different age groups. METHODS: A prospective, multicenter cohort of 11,602 unilateral primary TKA patients was evaluated. Demographic data, comorbid conditions, and patient-reported outcome measures including the knee injury and osteoarthritis outcome score (KOOS), KOOS-12, KOOS Joint Replacement, and Short-Form health survey (12-item) were collected preoperatively and at 1-year postoperatively. Descriptive statistics were generated, stratified by age [<55 years (younger adult), 55 to 64 years (older adult), 65 to 74 years (early elder), and ≥ 75 years (late elder)], and differences in pain, function, and QoL among the 4 age groups were evaluated using Chi-square and Kruskal-Wallis tests. Multivariate regression models with 95% confidence interval were performed to determine if age was predictive for KOOS pain and function scores. RESULTS: Prior to surgery, younger patients (<55 years) reported worse KOOS pain (39), function (50), and QoL (18) scores with poor mental health score (47) than other older patient groups. The mean preoperative score differences across the age groups in the KOOS total score (9.37), KOOS pain (11.61), KOOS-12 pain (10.14), and KOOS/KOOS-12 QoL (12.60) reached the calculated minimal clinically important difference. At 1 year after TKA, younger patients (<55 years) reported lower KOOS pain, function, and QoL scores when compared to older patients (≥ 75 years). The differences in 1-year postop scores among the 4 age groups (ranging from 4.0 to 12.2) reached the minimal clinically important difference for pain (10.4) and QoL (12.2). Younger patients (<55 years) achieved higher baseline to 1-year pain (36.8 points), function (30.3 points), and QoL (40.7 points) score changes when compared to older patients aged ≥ 75 years. Although statistically significant, the differences in score changes among the age groups were clinically irrelevant. The multivariate regression analyses showed that age was a significant predictor for pain, but not for function at 1 year where KOOS pain score was predicted to be higher (less pain) (ß = 6.17; 95% confidence interval 4.12- 8.22) (P < .001) in older patients (≥ 75 years) when compared to younger patients (<55 years). CONCLUSION: A TKA provides a dramatic improvement in pain, function, and QoL in all age groups. However, there are age-related clinically significant differences in preoperative pain, QoL, and mental health and in final postoperative pain and QoL scores with younger patients (<55 years) reporting more pain, less QoL, and worse preoperative mental health. The patient-reported outcome measure data presented here can be used clinically to improve shared decision-making and patient expectations prior to TKA.

How Back Pain Affects Patient Satisfaction After Primary Total Knee Arthroplasty.

BACKGROUND: Although back pain (BP) has been shown to be a predictor of dissatisfaction after total knee arthroplasty (TKA) in some reports, these studies did not use a scale to quantify the degree of pain. The purpose of this study was to quantify the effect of BP intensity on patient satisfaction reported at 1 year after TKA. METHODS: A multicenter prospective cohort was taken in which 9,057 patients undergoing primary unilateral TKA were enrolled in FORCE-TJR and demographic and clinical data were collected. Back pain (BP) intensity was assessed using the Oswestry back disability index (ODI) pain intensity questionnaire. Patients were classified into 4 categories based on the severity of BP. Patient-reported outcomes (PROs) were collected preoperatively and postoperatively after 1 year including the Knee injury and Osteoarthritis Outcome Score (KOOS) (total score, pain, Activities of Daily Living (ADL), and Quality of Life (QOL), Short-Form health survey 36-item (SF-36) Physical Component Score (PCS), and Mental Component Score (MCS)). We used a validated 5-point Likert satisfaction scale. Univariate analyses of the difference between the satisfied and dissatisfied patients' groups was performed. Multivariate logistic regression models with 95% confidence interval (CI) were used to quantify the effect of BP intensity on patient dissatisfaction at 1 year. Receiver operating characteristic (ROC) analyses were performed with measurement of area under curve (AUC). RESULTS: At 1 year, a total of 1,657 TKA patients (18.3%) were dissatisfied. A total of 4,765 patients (52.6%) reported back pain at the time of surgery, including mild BP in 2,264 patients (24.9%), moderate BP in 1,844 patients (20.3%), and severe BP in 657 patients (7.2%). Severe back pain was significantly associated with patient dissatisfaction at 1 year after TKA (P = .0006). The multivariate regressions showed that patients who had severe BP were 1.6 times more likely to be dissatisfied when compared to patients who had no BP [odds ratio (OR) 1.63; 95% confidence interval (CI) (1.23-2.16), P = .0006]. While patients who had mild BP [OR 0.98; 95% CI (0.82-1.17), P = .87] or moderate BP [OR 0.97; 95% CI (0.80-1.18), P = .78] were not associated with an increased likelihood of dissatisfaction. Other predictive variables for dissatisfaction, include age [OR for younger patients <65 years versus older patients ≥65 years, 0.74; 95% CI (0.59-0.92)], educational level [OR for post high school versus less, 0.83; 95% CI (0.71, 0.97)], smoking [OR for nonsmoker versus current smoker, 0.63; 95% CI (0.45, 0.87)], and Charlson comorbidity index [OR for CCI ≥2 versus 0, 1.25; 95% CI (1.05, 1.49)]. CONCLUSION: Increased BP intensity was associated with increased risk of dissatisfaction 1 year after TKA. Only patients who had severe BP were 1.6 times more likely to be dissatisfied. The data presented here can help to improve shared decision-making and patient counseling before surgery. Surgeons should consider a spine evaluation in patients who have severe BP prior to TKA.

The Prevalence and Predictors of Patient Dissatisfaction 5-years Following Primary Total Knee Arthroplasty.

BACKGROUND: Previous studies have evaluated patient dissatisfaction after total knee arthroplasty (TKA) at 1 year, but there is no data about the prevalence of dissatisfaction among TKA patients after prolonged follow-up. The purpose of this study is to determine patient dissatisfaction 5-years after TKA and to identify patient factors predictive of dissatisfaction. METHODS: Demographic and clinical data on 4402 patients undergoing primary unilateral TKA between 2012 and 2015 were collected prospectively through the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) comparative effectiveness consortium including diverse community and academic practices distributed across 23 states in the United States. Data collected at 1 year preoperatively and 5 years postoperatively included patient satisfaction (using a 5-point Likert satisfaction scale) and patient-reported outcome measures (PROMs) including the Knee injury and Osteoarthritis Outcome Score (KOOS) and Short-Form health survey (36-item). A univariate analysis of the difference between the satisfied and dissatisfied patients' groups was performed. A multivariate logistic regression model with 95% confidence interval (CI) was used to identify independent predictors of dissatisfaction at 5 years. The regression model was performed after adjusting the following variables: age, gender, body mass index (BMI), Charlson Comorbidity Index (CCI), marital status, smoking, education, and insurance type. The Receiver Operating Characteristic (ROC) analysis was performed with the measurement of area under curve (AUC). Hosmer-Lemeshow goodness of fit test was performed to evaluate the validity of the model. RESULTS: A total of 12.7% patients (559/4402) reported dissatisfaction 5-years after TKA. Increased BMI, higher CCI, higher Oswestry disability index, and increased number of other painful lower extremities (LE) joints were significantly associated with dissatisfaction. Higher rates of dissatisfaction were present in young patients, patients with less education, and non-White patients. Patient dissatisfaction was significantly associated with poor preoperative and 5-year postoperative PROMs scores and less score improvement from baseline to 5 years (P < .001). The multivariate regression analysis showed that an increased number of other painful LE joints (OR = 1.81; 95% CI (1.14-2.88) (P = .01), increased Oswestry back disability index (OR = 1.40; 95% CI (1.07-1.82) (P = .01), non-White patients (OR = 1.74; 95% CI (1.26-2.40) (P = .001), and minimal preoperative functional disability with KOOS function in daily living (ADL) score ≥70 (OR = 0.64; 95% CI (0.43-0.95) (P = .02) were independent predictive factors for dissatisfaction at 5 years. CONCLUSION: A total of 12.7% patients reported dissatisfaction 5-years after TKA. Clinical profiles of the satisfied and dissatisfied patients were captured 5-years after TKA with differences in the preoperative demographic and clinical characteristic variables identified. Risk factors for long-term patient dissatisfaction after TKA have been identified and should be considered during shared decision making while planning for TKA. Surgeons should use these identified risk factors to set realistic expectations for patients at an increased risk for dissatisfaction aiming to optimize their outcomes and increase their long-term satisfaction after TKA.

Do Patient Outcomes Vary by Patient Age Following Primary Total Hip Arthroplasty?

BACKGROUND: Multiple authors have sought to determine what patient characteristics influence outcome after total hip arthroplasty (THA). Age has shown no effect on outcome in some evaluations, while others have reported higher functional improvement in younger patients. The aim of this study was to determine if outcome after THA varies based on patient age. METHODS: A prospective, multicenter cohort of 7,934 unilateral primary THA patients from the FORCE-TJR comparative effectiveness consortium was evaluated. Demographic data, comorbid conditions, and Patient-Reported Outcome Measures, including (HOOS), HOOS-12, HOOS JR, and SF-36 (PCS) and (MCS), were collected preop and at 1-year postop. Descriptive statistics were generated, stratified by age (<55 years [younger adult], 55-64 years [older adult], 65-74 years [early elder], and ≥75 years [late elder]), and differences in pain, function, and quality of life among the 4 age groups were evaluated. A multivariate regression model with 95% confidence interval (CI) was used to assess the role of patient age as a predictive factor for HOOS pain and function scores reported 1 year after primary THA. RESULTS: Prior to surgery, younger patients (<55 years) reported worse pain, function, and quality of life than the other 3 patient groups. At 1 year after THA, younger patients (<55 years) reported slightly worse pain and quality of life but better function scores than the 3 older patients' groups. Younger patients (<55 years) achieved higher baseline to 1-year pain, and function score changes when compared to the older patients' groups. The quality of life score changes was not different among the 4 age groups. The differences in 1-year postop scores (ranging from 2.74 to 8.46) and the magnitude of score changes from baseline to 1 year (ranging from 1.9 to 5.85), although statistically significant (P < .001), did not reach the minimal clinically important difference (MCID). The multivariate regression analysis shows that age is a significant predictor for pain at 1 year but not for function. Although HOOS pain score is predicted to be higher by 4.38 points (less pain) 1 year after THA in older patients (≥75), when compared to younger patients (<55 years), again the difference is well below the MCID and is clinically insignificant. CONCLUSION: Although there are statistically significant differences in pain relief, functional improvement, and quality of life between younger and older patients among different patients' age groups, there is no clinically significant difference. THA provides an improvement in quality of life by decreasing pain and increasing function in all 4 age groups, with large improvements in Patient-Reported Outcome Measures scores (>2 standard deviations) without clinically significant age-related differences in THA outcome at 1 year.

Challenging Diagnosis of Stickler Syndrome in a Patient with Premature Osteoarthritis: A Case Report.

CASE: A 53-year-old male patient, subsequently diagnosed with type I Stickler syndrome, presented with severe premature osteoarthritis associated with bilateral hip dysplasia and knee epiphyseal dysplasia. Despite the presence of the typical manifestations of orofacial defects, hearing, ocular, and musculoskeletal abnormalities, the patient had never been diagnosed with the syndrome. CONCLUSION: Stickler syndrome can present with a wide spectrum of musculoskeletal abnormalities without previous diagnosis. It is often underrecognized if the manifestations of other systems are not appreciated. Stickler syndrome should be considered in the differential diagnosis of patients with unexplained musculoskeletal abnormality particularly in the presence of other system manifestations.

Multiple Joint Osteonecrosis in a Patient on Long-term Intranasal Corticosteroids.

We present the first report of bilateral knee and left ankle osteonecrosis in a 58-year-old female patient on long-term intranasal corticosteroids. Initially, our patient presented with progressive disabling knee pain with normal radiographs. The patient was presumed to have mild degenerative joint disease; therefore, she was treated conservatively. Then, the patient developed severe left ankle pain, and she was thought to have L5/S1 radiculopathy; therefore, she underwent epidural steroid injection that did not provide any benefit. However, extensive bilateral osteonecrosis of the medial tibial plateau in addition to osteonecrosis of the talus bone of left ankle were later diagnosed by MRI. The patient underwent staged bilateral total knee arthroplasty. In conclusion, the diagnosis of osteonecrosis might be challenging because of overlapping clinical presentation with other disorders particularly in the early stage of the disease with normal radiographs. Therefore, a high index of suspicion and thorough history with supplemental MRI imaging are essential for the assessment of patients presented with atypical refractory joint pain particularly in the presence of risk factors.

Surface-grafted zwitterionic polymers improve the efficacy of a single antibiotic injection in suppressing S. aureus periprosthetic infections.

Implant-associated bacterial infections are difficult to treat due to the tendency of biofilm formation on implant surfaces, which protects embedded pathogens from host defense and impedes antibiotic penetration, rendering systemic antibiotic injections ineffective. Here, we test the hypothesis that implant coatings that reduce bacterial colonization would make planktonic bacteria within the periprosthetic environment more susceptible to conventional systemic antibiotic treatment. We covalently grafted zwitterionic polymer brushes poly(sulfobetaine methacryate) from Ti6Al4V surface to increase the substrate surface hydrophilicity and reduce staphylococcus aureus (S. aureus) adhesion. Using a mouse femoral intramedullary (IM) canal infection model, we showed that the anti-fouling coating applied to Ti6Al4V IM implants, when combined with a single vancomycin systemic injection, significantly suppressed both bacterial colonization on implant surfaces and the periprosthetic infections, outperforming either treatment alone. This work supports the hypothesis that grafting anti-fouling polymers to implant surfaces improves the efficacy of systemic antibiotic injections to combat periprosthetic infections.

Significant Suppression of Staphylococcus aureus Colonization on Intramedullary Ti6Al4V Implants Surface-Grafted with Vancomycin-Bearing Polymer Brushes.

Orthopedic implant-associated bacterial infection presents a major health threat due to tendency for periprosthetic bacterial colonization/biofilm formation that protects bacteria from host immune response and conventional antibiotic treatment. Using surface-initiated atom transfer radical polymerization and copper-catalyzed azide-alkyne cycloaddition (CuAAC), alkynylated vancomycin is conjugated to azido-functionalized side chains of polymethacrylates grafted from Ti6Al4V. High-efficiency CuAAC across the substrate is confirmed by complete surface conversion of azides by X-ray photoelectron spectroscopy (XPS) and elemental mapping of changing characteristic elements. The vancomycin-modified surface (Ti-pVAN) significantly reduces in vitro adhesion and colonization of Staphylococcus aureus (S. aureus), a main bacterial pathogen responsible for periprosthetic infection and osteomyelitis, compared to untreated Ti6Al4V, supporting retained antibacterial properties of the covalently conjugated antibiotics. When the surface-modified intramedullary Ti-pVAN pins are inserted into mouse femoral canals infected by bioluminescent Xen29 S. aureus, significantly reduced local bioluminescence along with mitigated blood markers for infection are detected compared to untreated Ti6Al4V pins over 21 days. Ti-pVAN pins retrieved after 21 days are confirmed with ∼20-fold reduction in adherent bacteria counts compared to untreated control, supporting the ability of surface-conjugated vancomycin in inhibiting periprosthetic S. aureus adhesion and colonization.

Multifunctional scaffolds for facile implantation, spontaneous fixation, and accelerated long bone regeneration in rodents.

Graft-guided regenerative repair of critical long bone defects achieving facile surgical delivery, stable graft fixation, and timely restoration of biomechanical integrity without excessive biotherapeutics remains challenging. Here, we engineered hydration-induced swelling/stiffening and thermal-responsive shape-memory properties into scalable, three-dimensional-printed amphiphilic degradable polymer-osteoconductive mineral composites as macroporous, non-load-bearing, resorbable synthetic grafts. The distinct physical properties of the grafts enabled straightforward surgical insertion into critical-size rat femoral segmental defects. Grafts rapidly recovered their precompressed shape, stiffening and swelling upon warm saline rinse to result in 100% stable graft fixation. The osteoconductive macroporous grafts guided bone formation throughout the defect as early as 4 weeks after implantation; new bone remodeling correlated with rates of scaffold composition-dependent degradation. A single dose of 400-ng recombinant human bone morphogenetic protein-2/7 heterodimer delivered via the graft accelerated bone regeneration bridging throughout the entire defect by 4 weeks after delivery. Full restoration of torsional integrity and complete scaffold resorption were achieved by 12 to 16 weeks after surgery. This biomaterial platform enables personalized bone regeneration with improved surgical handling, in vivo efficacy and safety.

Modulating Viscoelasticity, Stiffness, and Degradation of Synthetic Cellular Niches via Stoichiometric Tuning of Covalent versus Dynamic Noncovalent Cross-Linking.

Viscoelasticity, stiffness, and degradation of tissue matrices regulate cell behavior, yet predictive synergistic tuning of these properties in synthetic cellular niches remains elusive. We hypothesize that reversible physical cross-linking can be quantitatively introduced to synthetic hydrogels to accelerate stress relaxation and enhance network stiffness, while strategic placement of isolated labile linkages near cross-linking sites can predict hydrogel degradation, both of which are essential for creating adaptive cellular niches. To test these hypotheses, chondrocytes were encapsulated in hydrogels formed by biorthogonal covalent and noncovalent physical cross-linking of a pair of hydrophilic building blocks. The stiffer and more viscoelastic hydrogels with DBCO-DBCO physical cross-links facilitated proliferation and chondrogenic ECM deposition of encapsulated cells by dissipating stress imposed by expanding cell mass/ECM via dynamic disruption/reformation of physical cross-links. Degradation of labile linkages near covalent cross-linkers further facilitated cell proliferation and timed cell release while maintaining chondrogenic phenotype. This work presents new chemical tools for engineering permissive synthetic niches for cell encapsulation, 3D expansion, and release.

A Web-Based Treatment Decision Support Tool for Patients With Advanced Knee Arthritis: Evaluation of User Interface and Content Design.

BACKGROUND: Data-driven surgical decisions will ensure proper use and timing of surgical care. We developed a Web-based patient-centered treatment decision and assessment tool to guide treatment decisions among patients with advanced knee osteoarthritis who are considering total knee replacement surgery. OBJECTIVE: The aim of this study was to examine user experience and acceptance of the Web-based treatment decision support tool among older adults. METHODS: User-centered formative and summative evaluations were conducted for the tool. A sample of 28 patients who were considering total knee replacement participated in the study. Participants' responses to the user interface design, the clarity of information, as well as usefulness, satisfaction, and acceptance of the tool were collected through qualitative (ie, individual patient interviews) and quantitative (ie, standardized Computer System Usability Questionnaire) methods. RESULTS: Participants were older adults with a mean age of 63 (SD 11) years. Three-quarters of them had no technical questions using the tool. User interface design recommendations included larger fonts, bigger buttons, less colors, simpler navigation without extra "next page" click, less mouse movement, and clearer illustrations with simple graphs. Color-coded bar charts and outcome-specific graphs with positive action were easiest for them to understand the outcomes data. Questionnaire data revealed high satisfaction with the tool usefulness and interface quality, and also showed ease of use of the tool, regardless of age or educational status. CONCLUSIONS: We evaluated the usability of a patient-centered decision support tool designed for advanced knee arthritis patients to facilitate their knee osteoarthritis treatment decision making. The lessons learned can inform other decision support tools to improve interface and content design for older patients' use.

Anionic and Zwitterionic Residues Modulate Stiffness of Photo-Cross-Linked Hydrogels and Cellular Behavior of Encapsulated Chondrocytes.

Photo-cross-linked poly(ethylene glycol) dimethacrylate (PEGDMA) hydrogels have been widely utilized for cartilage tissue engineering. However, strategies for improving their stiffness have been predominantly limited to increasing the degree of photo-cross-linking or weight fraction of the polymer. In this study, we tested the hypothesis that covalent incorporation of anionic sulfonate or zwitterionic sulfobetaine residues into photo-cross-linked PEGDMA hydrogels could enhance their mechanical properties without altering overall polymer content or swelling behavior. In addition, we investigated whether and how covalent incorporation of these chemical residues would affect cartilage extracellular matrix secretion by encapsulated chondrocytes. With the incorporation of 5-10% anionic or zwitterionic residues, the compressive moduli of PEGDMA hydrogels increased and the stress relaxation expedited while the swelling behavior and overall polymer fraction were kept the same. The incorporation of anionic residues exerted a more profound incorporation content-dependent impact on compressive moduli than zwitterionic residues. Higher-content incorporation of the anionic residue (10% vs 5%) also reduced the metabolic activity and type II collagen secretion by encapsulated murine chondrocytes and limited the pericellular diffusion of secreted proteoglycans within the 3D hydrogel. Although encapsulated human chondrocytes exhibited different sensitivity to serum level in culture than murine chondrocytes, the general trend of the impact of covalent incorporation of the chemical residues on their ECM secretion was the same. Overall, covalent incorporation of anionic and zwitterionic residues at an appropriate content presents a viable alternative to increasing the degree of photo-cross-linking for modulating the stiffness of PEGDMA hydrogels and the metabolism and phenotypical matrix secretion by encapsulated chondrocytes. It underscores the significance of noncovalent interactions imposed by charged residues in modulating biomechanical and cellular properties in tissue engineering scaffold designs.

Functional Gain and Pain Relief After Total Joint Replacement According to Obesity Status.

BACKGROUND: Obesity has been associated with lower function and more pain before and after total hip or knee replacement (THR or TKR). We examined the changes between preoperative and postoperative function and pain in a large representative U.S. cohort to determine if there was a relationship to obesity status. METHODS: Preoperative and 6-month postoperative data on function (Short Form-36 Physical Component Summary [PCS] score), joint pain (Hip disability and Osteoarthritis Outcome Score and Knee injury and Osteoarthritis Outcome Score), and body mass index (BMI) were collected from a national sample of 2,040 patients who had undergone THR and 2,964 who had undergone TKR from May 2011 to March 2013. Preoperative and postoperative function and pain were evaluated according to BMI status, defined as under or of normal weight, overweight, obese, severely obese, or morbidly obese. RESULTS: Patients undergoing THR were an average of 65 years of age; 59% were women, 94% were white, and 14% were severely or morbidly obese. A greater obesity level was associated with a lower (worse) PCS score at baseline and 6 months postoperatively. Severely and morbidly obese patients had less postoperative functional gain than the other BMI groups. A greater obesity level was associated with more pain at baseline but greater postoperative pain relief, so the average postoperative pain scores did not differ significantly according to BMI status. Patients undergoing TKR had an average age of 69 years; 61% were women, 93% were white, and 25% were severely or morbidly obese. A greater obesity level was associated with a lower PCS score at baseline and 6 months. The postoperative gain in PCS score did not differ by BMI level. A greater obesity level was associated with worse pain at baseline but greater pain relief at 6 months, so the average pain scores at 6 month were similar across the BMI levels. CONCLUSIONS: Six months after total joint replacement (TJR), severely or morbidly obese patients reported excellent pain relief and substantial functional gain that was similar to the findings in other patients. While obesity is associated with a greater risk of early complications, obesity in itself should not be a deterrent to undergoing TJR to relieve symptoms. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.