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Human adipose-derived mesenchymal stem cells (ASCs) transduced with a lentiviral vector system to express bone morphogenetic protein 2 (LV-BMP-2) have been shown to reliably heal bone defects in animal models. However, the influence of donor characteristics such as age, sex, race, and medical co-morbidities on ASC yield, growth and bone regenerative capacity, while critical to the successful clinical translation of stem cell-based therapies, are not well understood. Human ASCs isolated from the infrapatellar fat pads in 122 ASC donors were evaluated for cell growth characteristics; 44 underwent additional analyses to evaluate in vitro osteogenic potential, with and without LV-BMP-2 transduction. We found that while female donors demonstrated significantly higher cell yield and ASC growth rates, age, race, and the presence of co-morbid conditions were not associated with differences in proliferation. Donor demographics or the presence of comorbidities were not associated with differences in in vitro osteogenic potential or stem cell differentiation, except that transduced ASCs from healthy donors produced more BMP-2 at day 2. Overall, donor age, sex, race, and the presence of co-morbid conditions had a limited influence on cell yield, proliferation, self-renewal capacity, and osteogenic potential for non-transduced and transduced (LV-BMP-2) ASCs. These results suggest that ASCs are a promising resource for both autologous and allogeneic cell-based gene therapy applications.

Background Pain management is a critical component of comprehensive postsurgical care, as it influences patient safety and outcomes, and inadequate control has been associated with the development of chronic pain syndromes. Despite recent improvements, the management of postoperative pain following total knee arthroplasty (TKA) remains a challenge. The use of opioid-sparing, multimodal analgesic regimens has broad support, but there is a paucity of high-quality evidence regarding optimal postoperative protocols and novel approaches are needed. Dextromethorphan stands out among both well-studied and emerging pharmacological adjuncts for postoperative pain due its robust safety profile and unique pharmacology. The purpose of this study is to evaluate the efficacy of multi-dose dextromethorphan for postoperative pain control following TKA. Methods This is a single-center, multi-dose, randomized, double-blinded, placebo-controlled trial. A total of 160 participants will be randomized 1:1 to receive either 60 mg oral dextromethorphan hydrobromide preoperatively, as well as 30 mg 8 h and 16 h postoperatively, or matching placebo. Outcome data will be obtained at baseline, during the first 48 h, and the first two follow-up visits. The primary outcome measure will be total opioid consumption at 24 h postoperatively. Secondary outcomes related to pain, function, and quality of life will be evaluated using standard pain scales, the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR) questionnaire, the Patient-Reported Outcomes Measurement Information System (PROMIS-29) questionnaire, and clinical anchors. Discussion This study has a number of strengths including adequate power, a randomized controlled design, and an evidence-based dosing schedule. As such, it will provide the most robust evidence to date on dextromethorphan utilization for postoperative pain control following TKA. Limitations include not obtaining serum samples for pharmacokinetic analysis and the single-center study design. Trial registration This trial has been registered on the National Institute of Health’s ClinicalTrials.gov (NCT number: NCT05278494). Registered on March 14, 2022.

In this study, the in vitro fixation of four otherwise identical double-tapered stem-types, varying only in surface finish (polished or matte) and proximal stem geometry (with or without flanges) were compared under two conditions. First, four specimens of each stem type were tested with initially bonded stem–cement interfaces, representing early post-operative conditions. Then, simulating conditions a few weeks to months later, stems were implanted in unused synthetic femurs, with a thin layer coating the stem to prevent stem–cement adhesion. Per-cycle motions were measured at both cement interfaces throughout loading. Overall, surface finish had the smallest relative effect on fixation compared to flanges. Flanges increased axial fixation by 22 μm per-cycle, regardless of surface finish ( P=0.01). Further, all stems moved under dynamic load at the stem–cement interface during the first few cycles of loading, even without a thin film. The results indicate that flanges have a greater effect on fixation than surface finish, and therefore adverse findings about matte surfaces should not necessarily apply to all double-tapered stems. Specifically, dorsal flanges enhance the stability of a tapered cemented femoral stem, regardless of surface finish.

Long-term clinical follow-up studies have shown that radiolucent lines at the cement interfaces of total hip replacement femoral components develop gradually, ultimately leading to loosening. In this experimental study, 32 synthetic femurs implanted with cemented femoral components were cyclically loaded with a dynamic joint reaction force, torque, and muscle force, to assess the relative effects of surface finish and collars on interface fixation. Four each of four otherwise identical straight femoral stems, varying only in surface finish and presence or lack of collars were used. Specimens were tested under two conditions: (1) with intact interfaces simulating immediate post-operative conditions and (2) with a thin-film at the stem–cement interface, simulating conditions several weeks to months post-operative when fibrous tissue has formed with the implant still stable. Micromotion was measured at both interfaces in three directions. Surface finish had a larger relative effect than collars, regardless of whether or not a thin-film was present. For example, a proximal grit-blasted finish enhanced fixation at the stem–cement interface by 7–12 μm per-cycle ( p<0.05) and decreased early cement mantle loosening by 7–13 μm. For straight stems, rougher surfaces provided greater stability than polished, even with a thin film at the stem–cement interfaces, contradicting the theory that once debonded, rough stems are less stable than polished at the stem–cement interface. The findings of this experimental study exemplify the need to take advantage of all available tools for the preclinical evaluation of orthopaedic implants, including long-term clinical observations of related devices, analytical and numeric models, and experimental bench-top simulations.

BACKGROUND:The optimum surface roughness of cemented femoral stems used for total hip replacement is a subject of controversy. While rougher surfaces provide stronger cement adhesion, it has been hypothesized that polished, tapered, noncollared stems settle into the cement mantle, providing improved stability. However, the effects of surface finish on the stability of straight, cemented stems tapered only in the coronal plane are not known. METHODS:Using composite model femora, we assessed the initial stability of a straight, cemented femoral stem as a function of surface roughness, the presence or absence of a collar, stem size, and the resultant cement thickness under simulated walking and stair-climbing loads. Otherwise identical stems were manufactured with polished or rough surfaces, with or without a collar, in two different sizes. We isolated these three variables and compared their relative contributions to the motion at the stem-cement interface throughout cyclic loading. We defined three indicators of stabilityper-cycle motion, rate of migration, and final migration. RESULTS:Surface roughness had a greater influence on per-cycle motions than did the presence or absence of a collar or cement thickness. Specifically, in the medial-lateral direction, per-cycle motion of polished stems was 43 μm greater than that of rough stems (p < 0.01). None of the per-cycle motions decreased over the 77,000 load cycles. In contrast, with all stems, the rate of migration decreased over the course of cyclic loading, but the rate of migration of the polished stems was greater than that of the rough stems. Final migrations of the stems over the course of loading were generally distal, medial, and into retroversion. Compared with rough stems, polished stems had 8 to 18 μm more axial migration (p < 0.001), 48 μm more anterior-posterior migration (p < 0.001), and 0.4° more rotational migration (p = 0.01). CONCLUSIONS AND CLINICAL RELEVANCE:The results indicated that, for cemented, straight femoral stems tapered only in the coronal plane, a rough surface offers the advantage of less per-cycle motion. These results may apply to widely used cemented stem designs based on the profile of the original Charnley femoral component, which has approximately parallel anterior and posterior aspects.

BackgroundAlthough current designs of cemented femoral stems for total hip replacement include both those with and those without a flanged shape at the proximal end, the influence of anteroposterior dorsal flanges on the fixation of the stem is not completely understood. The purpose of this study was to assess the effects of flanges on femoral stem stability and load transfer to the femur with use of an in vitro model.MethodsWe measured femoral surface strains and three-dimensional micromotion in synthetic femora under cyclic loading with four types of stemsthose with flanges and those without flanges in two sizes each. The four types of stems were otherwise identical; that is, all of them were straight, polished, and collarless. Stem-cement micromotion measurements and strain measurements were repeated with three stems of each type, whereas bone-cement micromotion measurements were made with one stem of each type.ResultsFlanges had a greater influence on femoral strains and micromotion than did the difference in the cement thickness resulting from the different stem sizes. Specifically, the flanged stems produced greater strains on the medial femoral surface but smaller strains on the anterior surface than did the non-flanged stems. Flanged stems achieved tighter mechanical interlock within the cement, but these stems increased bone-cement micromotion. Specifically, the motion per cycle of flanged stems within the cement mantle was smaller than that of non-flanged stems, whereas the motion per cycle of the cement mantle within the femoral canal was greater with the flanged stems than with the non-flanged stems.ConclusionsFlanges on a total hip femoral stem increase the interlock between the stem and the cement and decrease the proximal-medial stress-shielding. However, these advantages occur with increased bone-cement interface motion, which may be detrimental to the survival of the implant.Clinical RelevanceThe findings help to predict the consequences of the use of dorsal flanges for femoral stems and should be considered in the design of new femoral stems.

BackgroundTotal hip replacements with a metal-on-metal articulation were commonly used until the mid-1970s; most were then abandoned in favor of hip replacement with a metal-on-polyethylene articulation. The reason for this change was primarily early cup loosening, which was more prevalent with these metal-on-metal designs than it was with metal-on-polyethylene designs. In the late 1980s, a metal-on-metal design with improved clearance (adequate space between the femoral head and the acetabular articulation surface to allow fluid film lubrication and clearance of any debris from within this joint), metal hardness, and reproducible surfaces was introduced by Sulzer Orthopedics in Switzerland. Orthopaedic surgeons were interested in this Metasul articulation because the contribution of polyethylene wear particles to the failure of total hip replacements had become evident. This study was undertaken to review the clinical performance of this implant and to determine if early acetabular loosening or revision and wear and osteolysis were prevalent.MethodsBetween 1991 and 1994, seventy patients (seventy hips) had a total hip replacement with the Metasul metal-on-metal articulation and a cemented Weber cup. Nine patients died less than four years after the replacement; none of these deaths were related to the operation. Five patients were not available for radiographic evaluation, but they were contacted and it was known that the hip was not painful and had not been revised. Fifty-six patients (fifty-six hips) had complete clinical and radiographic data four to 6.8 years after the operation, and they made up the study group. The patients were evaluated with use of the Harris hip score, a patient-self-assessment form, and radiographs.ResultsAt an average of 5.2 years (range, four to 6.8 years) after the operation, the average total Harris hip score for the fifty-three patients who did not have a revision was 89.6 points (range, 62 to 100 points). The average Harris pain score was 41.0 points (range, 30 to 44 points), and the average Harris limp score was 9.4 points (range, 5 to 11 points). One patient had revision of a loose cup, but there were no other loose acetabular components in the series. Two patients had revision of the acetabular component because of dislocation. No patient had a loose or revised femoral component. Therefore, the mechanical failure rate was one (2 percent) of fifty-six patients. Thirty-six of forty-seven patients who completed the patient-self-assessment form rated their result as excellent; seven, as very good; two, as good; one, as fair; and one, as poor. Wear could not be measured on radiographs because of the metal-on-metal articulation. No hip had radiographic evidence of acetabular osteolysis and two hips had calcar resorption, but there was no other radiographic evidence of focal osteolysis.ConclusionsOur four to seven-year experience with this articulation surface indicates that the clinical results are similar to those of total hip replacements with a metal-on-polyethylene articulation. We believe that the Metasul articulation may have a role in reducing the wear that occurs with total hip replacement. The Metasul articulation appears to be particularly indicated for more active patients. A historical comparison with the reports in the literature of which we are aware indicated that the hips in our study had a lower rate of acetabular revision and loosening than did those with previous metal-on-metal designs and that they had no more acetabular loosening or osteolysis than did those with metal-on-polyethylene articulations followed for an average of five years.

BACKGROUND: Total hip replacements with a metal-on-metal articulation were commonly used until the mid-1970s; most were then abandoned in favor of hip replacement with a metal-on-polyethylene articulation. The reason for this change was primarily early cup loosening, which was more prevalent with these metal-on-metal designs than it was with metal-on-polyethylene designs. In the late 1980s, a metal-on-metal design with improved clearance (adequate space between the femoral head and the acetabular articulation surface to allow fluid film lubrication and clearance of any debris from within this joint), metal hardness, and reproducible surfaces was introduced by Sulzer Orthopedics in Switzerland. Orthopaedic surgeons were interested in this Metasul articulation because the contribution of polyethylene wear particles to the failure of total hip replacements had become evident. This study was undertaken to review the clinical performance of this implant and to determine if early acetabular loosening or revision and wear and osteolysis were prevalent. METHODS: Between 1991 and 1994, seventy patients (seventy hips) had a total hip replacement with the Metasul metal-on-metal articulation and a cemented Weber cup. Nine patients died less than four years after the replacement; none of these deaths were related to the operation. Five patients were not available for radiographic evaluation, but they were contacted and it was known that the hip was not painful and had not been revised. Fifty-six patients (fifty-six hips) had complete clinical and radiographic data four to 6.8 years after the operation, and they made up the study group. The patients were evaluated with use of the Harris hip score, a patient-self-assessment form, and radiographs. RESULTS: At an average of 5.2 years (range, four to 6.8 years) after the operation, the average total Harris hip score for the fifty-three patients who did not have a revision was 89.6 points (range, 62 to 100 points). The average Harris pain score was 41.0 points (range, 30 to 44 points), and the average Harris limp score was 9.4 points (range, 5 to 11 points). One patient had revision of a loose cup, but there were no other loose acetabular components in the series. Two patients had revision of the acetabular component because of dislocation. No patient had a loose or revised femoral component. Therefore, the mechanical failure rate was one (2 percent) of fifty-six patients. Thirty-six of forty-seven patients who completed the patient-self-assessment form rated their result as excellent; seven, as very good; two, as good; one, as fair; and one, as poor. Wear could not be measured on radiographs because of the metal-on-metal articulation. No hip had radiographic evidence of acetabular osteolysis and two hips had calcar resorption, but there was no other radiographic evidence of focal osteolysis. CONCLUSIONS: Our four to seven-year experience with this articulation surface indicates that the clinical results are similar to those of total hip replacements with a metal-on-polyethylene articulation. We believe that the Metasul articulation may have a role in reducing the wear that occurs with total hip replacement. The Metasul articulation appears to be particularly indicated for more active patients. A historical comparison with the reports in the literature of which we are aware indicated that the hips in our study had a lower rate of acetabular revision and loosening than did those with previous metal-on-metal designs and that they had no more acetabular loosening or osteolysis than did those with metal-on-polyethylene articulations followed for an average of five years.