Bone-targeting liposome formulation of Salvianic acid A accelerates the healing of delayed fracture Union in Mice.

Delayed fracture union is a significant clinical challenge in orthopedic practice. There are few non-surgical therapeutic options for this pathology. To address this challenge, we have developed a bone-targeting liposome (BTL) formulation of salvianic acid A (SAA), a potent bone anabolic agent, for improved treatment of delayed fracture union. Using pyrophosphorylated cholesterol as the targeting ligand, the liposome formulation (SAA-BTL) has demonstrated strong affinity to hydroxyapatite in vitro, and to bones in vivo. Locally administered SAA-BTL was found to significantly improve fracture callus formation and micro-architecture with accelerated mineralization rate in callus when compared to the dose equivalent SAA, non-targeting SAA liposome (SAA-NTL) or no treatment on a prednisone-induced delayed fracture union mouse model. Biomechanical analyses further validated the potent therapeutic efficacy of SAA-BTL. These results support SAA-BTL formulation, as a promising therapeutic candidate, to be further developed into an effective and safe clinical treatment for delayed bone fracture union.

Low wear rates seen in THAs with highly crosslinked polyethylene at 9 to 14 years in patients younger than age 50 years.

BACKGROUND: Patients 50 years or younger are at high risk for wear-related complications of their total hip arthroplasty (THA) because of their generally higher levels of activity. Highly crosslinked polyethylene (HXLPE) is believed to be more durable for this population than conventional polyethylene because of its improved wear; however, limited information is available on the wear of HXLPE in this population, particularly the wear of HXLPE when it articulates with alternative bearings like Oxinium (Smith & Nephew, Memphis, TN, USA). QUESTIONS/PURPOSES: The purpose of this study was to evaluate two questions relative to this population of patients undergoing THA. First, what was the linear and volumetric wear rate of HXLPE in patients 50 years or younger at a minimum followup of 9 years and was osteolysis observed in any of these hips? Given the potential for damage to the Oxinium femoral head surface, was the wear of HXLPE in the patients with this material similar to the other bearings or was there accelerated or runaway wear that was visible in any of the patients? METHODS: From November 1999 to April 2005, 105 THAs were performed in 95 patients 50 years of age or younger (mean, 42 years; range, 20-50 years). The mean body mass index was 30 kg/m(2) (range, 17-51 kg/m(2)).The mean followup was 12 years (range, 9-14 years). Two patients died, five patients (one bilateral) were lost to followup, and one hip was revised elsewhere for pain. The patients' information was not included in the study, which left 87 patients with 96 hips for analysis. Highly crosslinked polyethylene was the acetabular bearing for all of the hips. We analyzed the linear and volumetric wear of all of the hips using the Martell method. Eighty hips had the same diameter head (28 mm) allowing us to more accurately compare the different bearing materials. The type of femoral head used was related to our sequential use of materials beginning with cobalt chrome (14), ceramic (23) followed by Oxinium (43) in the hips with 28-mm heads. Although cobalt-chrome was used early in this study, our previous experience with ceramic on polyethylene encouraged us to use it as an alternative bearing. The Oxinium was used consecutively for the remaining hips. RESULTS: The mean wear of the HXLPE after 1 year of bedding-in (true linear wear)was 0.022 mm/year (95% confidence interval [CI], 0.015-0.030 mm/year). The mean volumetric wear of HXLPE after 1 year of bedding-in (true volumetric wear) was 9 mm(3)/year (95% CI, 4-14 mm(3)/year). None of the hip radiographs had evidence of loosening or osteolysis. Wear was not associated with femoral head material (p = 0.58 for linear wear/year versus head material and p = 0.52 for volumetric wear/year versus head material). CONCLUSIONS: In our study of patients 50 years of age or younger undergoing THA, the linear and volumetric wear rates of HXLPE were very low regardless of the bearing surface material. The laboratory concerns of Oxinium surface damage are serious but at this time we have not seen high wear of the HXLPE or osteolysis in this population. LEVEL OF EVIDENCE: Level III, therapeutic study.

Femoral fixation in revision total hip arthroplasty.

Management of the femur during revision total hip arthroplasty can be challenging. Strategies for femoral reconstruction are based on understanding the degree of femoral bone loss. Numerous options exist for femoral reconstruction depending on the quantity and quality of the remaining femoral bone stock, including cemented fixation, cementless fixation using proximally porous-coated implants, cylindrical extensively porous-coated implants, modular and nonmodular tapered fluted stems, impaction bone grafting, allograft-prosthetic composites, and proximal femoral replacements (megaprostheses). An understanding of the results of various methods of femoral reconstruction is helpful in guiding the revision surgeon faced with a challenging femoral revision.

Pain associated with cemented and uncemented long-stemmed tibial components in revision total knee arthroplasty.

AIMS: Stemmed tibial components are frequently used in revision total knee arthroplasty (TKA). The purpose of this study was to evaluate patient satisfaction, overall pain, and diaphyseal tibial pain in patients who underwent revision TKA with cemented or uncemented stemmed tibial components. METHODS: This is a retrospective cohort study involving 110 patients with revision TKA with cemented versus uncemented stemmed tibial components. Patients who underwent revision TKA with stemmed tibial components over a 15-year period at a single institution with at least two-year follow-up were assessed. Pain was evaluated through postal surveys. There were 63 patients with cemented tibial stems and 47 with uncemented stems. Radiographs and Knee Society Scores were used to evaluate for objective findings associated with pain or patient dissatisfaction. Postal surveys were analyzed using Fisher's exact test and the independent-samples t-test. Logistic regression was used to adjust for age, sex, and preoperative bone loss. RESULTS: No statistically significant differences in stem length, operative side, or indications for revision were found between the two cohorts. Tibial pain at the end of the stem was present in 25.3% (16/63) of cemented stems and 25.5% (12/47) of uncemented stems (p = 1.000); 74.6% (47/63) of cemented patients and 78.7% (37/47) of uncemented patients were satisfied following revision TKA (p = 0.657). CONCLUSION: There were no differences in patient satisfaction, overall pain, and diaphyseal tibial pain in cemented and uncemented stemmed tibial components in revision TKA. Patient factors, rather than implant selection and surgical technique, likely play a large role in the presence of postoperative pain. Stemmed tibial components have been shown to be a possible source of pain in revision TKA. There is no difference in patient satisfaction or postoperative pain with cemented or uncemented stemmed tibial components in revision TKA. Cite this article: Bone Joint J 2021;103-B(6 Supple A):165-170.

Wear analysis in THA utilizing oxidized zirconium and crosslinked polyethylene.

UNLABELLED: Oxidized zirconium, a material with a ceramic surface on a metal substrate, and highly cross-linked polyethylene are two materials developed to reduce wear. We measured in vivo femoral head penetration in patients with these advanced bearings. We hypothesized the linear wear rates would be lower than those published for cobalt-chrome and standard polyethylene. We retrospectively reviewed a select series of 56 THAs in a relatively young, active patient population utilizing oxidized zirconium femoral heads and highly cross-linked polyethylene acetabular liners. Femoral head penetration was determined using the Martell computerized edge-detection method. All patients were available for 2-year clinical and radiographic followup. True linear wear was 4 microm/year (95% confidence intervals, +/- 59 microm/year). The early wear rates in this cohort of relatively young, active patients were low and we believe justify the continued study of these alternative bearing surfaces. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Surface nano-modification by ion beam-assisted deposition alters the expression of osteogenic genes in osteoblasts.

Biomaterials with enhanced biocompatibility are favored in implant studies to improve the outcomes of total joint replacement surgeries. This study tested the hypothesis that nano-structured surfaces for orthopedic applications, produced by the ion beam-assisted deposition method, would enhance osteointegration by altering the expression of bone-associated genes in osteoblasts. The ion beam-assisted deposition technique was employed to deposit nano-films on glass or titanium substrates. The effects of the ion beam-assisted deposition produced surfaces on the human osteosarcoma cell line SAOS-2 at the molecular level were investigated by assays of adhesion, proliferation, differentiation, and apoptosis on coated surfaces versus uncoated cobalt-chrome, as the control. Ion beam-assisted deposition nano-coatings enhanced bone-associated gene expression at initial cell adhesion, proliferation, and differentiation compared to cobalt-chrome surfaces as assessed by polymerase chain reaction techniques. Increased cell proliferation was observed using a nuclear cell proliferation-associated antigen. Moreover, enhanced cell differentiation was determined by alkaline phosphatase activity, an indicator of bone formation. In addition, programmed cell death assessed by annexin V staining and flow cytometry was lower on nano-surfaces compared to cobalt-chrome surfaces. Overall, the results indicate that nano-coated surfaces produced by the ion beam-assisted deposition technique for use on implants were superior to orthopedic grade cobalt-chrome in supporting bone cell adhesion, proliferation, and differentiation and reducing apoptosis. Thus, surface properties altered by the ion beam-assisted deposition technique should enhance bone formation and increase the biocompatibility of bone cell-associated surfaces.