Effects of bone mineral density at the lateral sclerotic boundary on the femoral head collapse onset in osteonecrosis of the femoral head: A preliminary study.

BACKGROUND: In the natural course of osteonecrosis of the femoral head, sclerotic changes at the boundary of necrotic lesion gradually occur until femoral head collapse. This study aims to examine the effects of bone mineral density at the lateral boundary of necrotic lesion on a subsequent femoral head collapse. METHODS: We developed patient-specific finite element models of 9 hips with subsequent collapse and 10 hips without subsequent collapse. Cubic regions of interest were selected at both subchondral areas of the lateral boundary and the adjacent necrotic lesion. Bone mineral density values of the regions of interest were quantitatively measured, and a ratio of bone mineral density values (lateral boundary/necrotic lesion) was calculated. Stress values at the lateral boundary were also evaluated. FINDINGS: The ratio of bone mineral density values was significantly higher in hips with subsequent collapse than that without subsequent collapse (p = 0.0016). The median equivalent stress and shear stress were significantly higher in hips with subsequent collapse than that without subsequent collapse (p = 0.0071, and p = 0.0143, respectively). The ratio of bone mineral density values showed a promising value in predicting the occurrence of subsequent femoral head collapse (AUC = 0.97). INTERPRETATION: Our results indicated that bone mineral density value at the lateral boundary of necrotic lesion may be associated with the occurrence of subsequent femoral head collapse in pre-collapse stage osteonecrosis of the femoral head.

Dynamic surface adapts to multiple service stages by orchestrating responsive polymers and functional peptides.

Control over the implant surface functions is highly desirable to enhance tissue healing outcomes but has remained unexplored to adapt to the different service stages. In the present study, we develop a smart titanium surface by orchestrating thermoresponsive polymer and antimicrobial peptide to enable dynamic adaptation to the implantation stage, normal physiological stage and bacterial infection stage. The optimized surface inhibited bacterial adhesion and biofilm formation during surgical implantation, while promoted osteogenesis in the physiological stage. The further temperature increase driven by bacterial infection induced polymer chain collapse to expose antimicrobial peptides by rupturing bacterial membranes, as well as protect the adhered cells from the hostile environment of infection and abnormal temperature. The engineered surface could inhibit infection and promote tissue healing in rabbit subcutaneous and bone defect infection models. This strategy enables the possibility to create a versatile surface platform to balance bacteria/cell-biomaterial interactions at different service stages of implants that has not been achieved before.

Relationship between the degree of subchondral collapse and articular surface irregularities in osteonecrosis of the femoral head.

Articular surface irregularities are often observed in collapsed femoral heads with osteonecrosis, while the effects of the degree of collapse on the articular surface are poorly understood. We first macroscopically assessed the articular surface irregularities on 2-mm coronal slices obtained using high-resolution microcomputed tomography of 76 surgically resected femoral heads with osteonecrosis. These irregularities were observed in 68/76 femoral heads, mainly at the lateral boundary of the necrotic region. The mean degree of collapse was significantly larger for femoral heads with articular surface irregularities than for those without (p < 0.0001). Receiver operating characteristic analysis showed that the cutoff value for the degree of collapse in femoral heads with articular surface irregularities at the lateral boundary was 1.1 mm. Next, for femoral heads with <3-mm collapse (n = 28), articular surface irregularities were quantitatively assessed based on the number of automatically counted negative curvature points. Quantitative evaluation showed that the degree of collapse was positively correlated with the presence of articular surface irregularities (r = 0.95, p < 0.0001). Histological examination of articular cartilage above the necrotic region (n = 8) revealed cell necrosis in the calcified layer and abnormal cellular arrangement in the deep and middle layers. In conclusion, articular surface irregularities of the necrotic femoral head depended on the degree of collapse, and articular cartilage was already altered even in the absence of macroscopically determined gross irregularities.

Posterior Pelvic Tilt in the Standing Position Might Be Associated with Collapse Progression in Post-Collapse Stage Osteonecrosis of the Femoral Head.

OBJECTIVE: Excessive pelvic tilt has been reported to impair the biomechanical loading of the hip joint. However, the influence of pelvic tilt in osteonecrosis of the femoral head (ONFH) remains unclear. This study aims to assess whether sagittal pelvic posture in the standing position correlates with progression of femoral head collapse in post-collapse stage ONFH. METHODS: This is a single-center retrospective study. We investigated 107 patients (107 hips; 73 males and 34 females; mean age, 48 years) diagnosed with Association of Research Circulation Osseous (ARCO) stage III ONFH at the first visit and who subsequently underwent surgical treatment in our institution from July 2016 to December 2020. The sagittal pelvic posture in the standing position before surgery was quantified as the angle formed by the anterior pelvic plane and the vertical z-axis in the sagittal view (APP angle). An APP angle <0° indicated posterior pelvic tilt. Progression of femoral head collapse was calculated as collapse speed. The following factors potentially associated with collapse speed were evaluated by exploratory data analysis followed with multiple linear regression analysis: sex, age, BMI, etiology, pelvic incidence, contralateral hip condition, time interval between the first visit and surgery, size of necrotic lesion, location of necrotic lesion, and APP angle. RESULTS: As ONFH progressed from ARCO stage IIIA to stage IV, APP angle decreased significantly and continuously (stage IIIA, -0.2° ± 5.5°; stage IIIB, -3.7° ± 5.8°; stage IV, -7.1° ± 6.4°). The factors significantly associated with collapse speed were size of necrotic lesion (p = 0.0079), location of necrotic lesion (p = 0.0190), and APP angle (p < 0.0001). APP angle showed a negative correlation with collapse speed (r = -0.40, p < 0.0001). After stratifying by size of necrotic lesion (<50% and ≥50% involvement) and location of necrotic lesion (JIC type C1 and C2), a significant negative correlation was observed between APP angle and collapse speed in each group (JIC type C1 with <50% involvement, r = -0.69, p < 0.0001; JIC type C1 with ≥50% involvement, r = -0.58, p = 0.0475; JIC type C2 with <50% involvement, r = -0.51, p = 0.0124; JIC type C2 with ≥50% involvement, r = -0.39, p = 0.0286). CONCLUSIONS: Our results suggest that posterior pelvic tilt in the standing position occurred as ONFH progressed from ARCO stage IIIA to stage IV, which might be associated with progression of femoral head collapse in ONFH.

Long noncoding RNA BS-DRL1 modulates the DNA damage response and genome stability by interacting with HMGB1 in neurons.

Long noncoding RNAs (lncRNAs) are known to regulate DNA damage response (DDR) and genome stability in proliferative cells. However, it remains unknown whether lncRNAs are involved in these vital biological processes in post-mitotic neurons. Here, we report and characterize a lncRNA, termed Brain Specific DNA-damage Related lncRNA1 (BS-DRL1), in the central nervous system. BS-DRL1 is a brain-specific lncRNA and depletion of BS-DRL1 in neurons leads to impaired DDR upon etoposide treatment in vitro. Mechanistically, BS-DRL1 interacts with HMGB1, a chromatin protein that is important for genome stability, and is essential for the assembly of HMGB1 on chromatin. BS-DRL1 mediated DDR exhibits cell-type specificity in the cortex and cerebellum in gamma-irradiated mice and BS-DRL1 knockout mice show impaired motor function and concomitant purkinje cell degeneration. Our study extends the understanding of lncRNAs in DDR and genome stability and implies a protective role of lncRNA against neurodegeneration.

Proximal femoral morphology after transtrochanteric posterior rotational osteotomy for osteonecrosis of the femoral head: A three-dimensional simulation study.

BACKGROUND: Transtrochanteric posterior rotational osteotomy (PRO) is one of the joint-preserving surgeries for osteonecrosis of the femoral head. In general, postoperative femoral neck-shaft varus realignment is planned to obtain a sufficient intact articular surface of the femoral head in the weight-bearing portion. Unlike anterior rotational osteotomy, PRO allows for more than 90° rotation of the femoral head, resulting in more complicated morphology. However, little is known about the potential risk of postoperative femoral retroversion after PRO. This simulation study aims: 1) to assess whether postoperative femoral neck-shaft varus realignment can coexist with preserved femoral anteversion after PRO, 2) and whether postoperative proximal femoral morphology could be predicted with approximation equations. HYPOTHESIS: High degree (>90°) PRO is favourable for femoral neck-shaft varus realignment, but unfavourable for maintaining postoperative femoral anteversion. MATERIALS AND METHODS: PRO was simulated by using CT data from 10 hips in 10 healthy volunteers. During simulation, the intertrochanteric osteotomy plane was determined three-dimensionally based on anteroposterior-view line (the osteotomy line on anteroposterior view) and lateral-view line (the osteotomy line on lateral view). By changing either the angle of anteroposterior-view line or lateral-view line, we simulated 90°, 110°, 130° and 150° PRO. To clarify the effects of various posterior rotation angles on postoperative proximal femoral morphology, we made simplified PRO models through changing only the posterior rotation angle. RESULTS: In the 90°, 110°, 130° and 150° PRO models, the vertically inclined angle of anteroposterior-view line showed a significant positive correlation with femoral neck-shaft varus realignment (90° PRO, r=0.90; 110° PRO, r=0.95; 130° PRO, r=0.97; 150° PRO, r=0.99), while a significant negative correlation with postoperative femoral anteversion angle (90° PRO, r=-0.97; 110° PRO, r=-0.95; 130° PRO, r=-0.92; 150° PRO, r=-0.7). Likewise, the posteriorly tilted angle of lateral-view line showed a significant negative correlation with both femoral neck-shaft varus realignment (90° PRO, r=-0.81; 110° PRO, r=-0.81; 130° PRO, r=-0.79; 150° PRO, r=-0.72) and postoperative femoral anteversion angle (90° PRO, r=-0.90; 110° PRO, r=-0.89; 130° PRO, r=-0.92; 150° PRO, r=-0.88). In the simplified PRO models, the posterior rotation angle showed a significant positive correlation with femoral neck-shaft varus realignment (r=0.33), while a significant negative correlation with postoperative femoral anteversion angle (r=-0.76). The approximation equations for predicting the proximal femoral morphology after PRO were validated. DISCUSSIONS: It was confirmed that high-degree PRO (>90°) is favourable for femoral neck-shaft varus realignment, but works against preserving femoral anteversion. With the approximation equations developed in the current study, surgeons could examine the feasibility of PRO based on postoperative femoral anteversion. In terms of hip joint function and subsequent total hip arthroplasty, excessive deformities including femoral retroversion and severe varus deformity could be avoided. LEVEL OF EVIDENCE: IV; case series without control group.

Conductive and antimicrobial macroporous nanocomposite hydrogels generated from air-in-water Pickering emulsions for neural stem cell differentiation and skin wound healing.

Electro-active conducting hydrogels have shown promising applications in promoting soft tissue regeneration. However, achieving good conductive performance while simultaneously imparting macroporous structures to these hydrogels still remains challenging. In this study, we report the development of multifunctional conductive macroporous nanocomposite hydrogels (MNHs) prepared by an air-in-water emulsion template that is stabilized by colloidal hybrids of carbon nanotubes (CNTs) and gelatin methacryloyl. The MNH hydrogels demonstrated tunable pore size, electrical conductivity and mechanical properties with various CNT concentrations in the crosslinking matrices. An in vitro cell assay showed that the MNH hydrogels could promote the spreading and differentiation of NE-4C neural stem cells. Furthermore, sustainable release of antimicrobial peptides (AMPs) from the MNH hydrogel can be achieved and the released AMPs maintained high S. aureus killing activity. An in vivo evaluation of the MNH hydrogel using a murine dorsal skin model further showed that the conductive MNH hydrogel loaded with AMPs demonstrated appealing antimicrobial and wound healing performance in two weeks.

Differences in the microarchitectural features of the lateral collapsed lesion between osteonecrosis and subchondral insufficiency fracture of the femoral head.

BACKGROUND: Like osteonecrosis of the femoral head (ONFH), subchondral insufficiency fracture of the femoral head (SIF) causes femoral head collapse. However, little is known about the differences between the two diseases regarding the morphological features of the collapsed lesion. We tested the hypothesis that the morphological features of the lateral collapsed lesion would differ between ONFH and SIF. METHODS: Twenty femoral heads histopathologically diagnosed as ONFH (n = 10) or SIF (n = 10) were used in this study. In the lateral collapsed lesion of each femoral head, cubic regions of interest (ROIs) were selected within the collapsed subchondral area and the nearby non-collapsed subchondral area. Micro-CT-based microarchitectural parameters were compared between the ROIs in each disease. Additionally, correlations between histopathological and microarchitectural features were evaluated. RESULTS: In ONFH, bone volume fraction, trabecular thickness, and bone mineral density in the collapsed area were all significantly lower than those in the nearby non-collapsed area where thickened bone trabeculae accompanied by appositional bone formation were invariably seen. On the other hand, in SIF there were no significant differences between the ROIs in any of these microarchitectural parameters. Histopathologically, varying degrees of callus formation overlying the fracture of the subchondral plate were seen around the lateral collapsed lesion. CONCLUSION: The morphological features of the lateral collapsed lesion were inconsistent between ONFH and SIF, suggesting different pathomechanisms of femoral head collapse.

Is bone mineral density lower in the necrotic lesion in pre-collapse osteonecrosis of the femoral head?

The purpose of this study was to clarify whether bone mineral density (BMD) of the necrotic lesion in precollapse osteonecrosis of the femoral head (ONFH) is reduced according to Hounsfield unit (HU) values on computed tomography (CT). The superior one-third of the femoral head in the coronal section was set as the region of interest (ROI) for the measurement of HU values. First, HU values of 101 control participants were assessed to identify relevant confounding factors. Next, the relationship between HU values and BMD on dual-energy X-ray absorptiometry (DXA) was verified. Then the mean HU value of the ROI in patients with pre-collapse ONFH was compared with that in propensity score-matched control participants. Finally, the HU values of the lateral boundary in the patients with and without subsequent collapse were compared. Multivariable analysis showed that both age and BMI were significantly correlated with the HU value, which showed a strong correlation with the BMD of the femoral neck on DXA (r = 0.92). In 25 ONFH patients and 25 propensity-matched control participants, no significant difference was found in the HU value of the ROI (p = .54). The mean HU value of the lateral boundary in patients with subsequent collapse was found to be significantly higher than that in patients without subsequent collapse (p < .01). The assessment of HU values on CT was useful for the evaluation of BMD of the femoral head. The current assessment did not demonstrate reduced bone mineral density of the necrotic lesion in pre-collapse ONFH.

[Surgical techniques and effectiveness of volar locking plates for senile delayed distal radius fractures].

Objective: To investigate the surgical technique and effectiveness of volar locking plates for senile delayed distal radius fractures. Methods: Between October 2014 and September 2015, 25 cases of delayed distal radius fractures were treated by volar locking plates. There were 3 males and 22 females with an average age of 73 years (range, 65-87 years). Injury was caused by tumble in 19 cases and by traffic accident in 6 cases. All the cases had closed fracture. According to the AO classification, 10 cases were rated as type A2, 7 cases as type A3, 3 cases as type B3, and 5 cases as type C1. The manual reduction and plaster immobilization were performed in 18 cases first, but reduction failed; no treatment was given in 7 cases before surgery. The time from injury to surgery was from 33 to 126 days (mean, 61 days). Preoperatively, the volar tilting angle was (-16.0±3.1)°; the ulnar inclining angle was (10.8±7.0)°; the radial shortening was (11.2±3.6) mm; the wrist range of motion was (41.0±7.5)° in flexion and was (42.0±6.3)° in extension; and the grip strength was 33.0%±3.1% of normal side. Results: All incisions healed primarily, and no postoperative complication occurred. The patients were followed up 1-1.5 years (mean, 1.3 years). The X-ray films showed that fracture union was achieved in all the patients, with the mean healing time of 9.2 weeks (range, 8-12 weeks); the displacement of the articular surface was less than 1 mm. At last follow-up, the volar tilting angle was (13.1±3.2)°; the ulnar inclining angle was (21.9±4.6)°; the radial shortening was (2.0±1.1) mm; the wrist range of motion was (52.0±11.7)° in flexion and was (65.0±4.8)° in extension; and the grip strength was 84.0%±4.2% of normal side; all showed significant difference when compared with preoperative ones ( P<0.05). According to the Gartland and Werley score, the results were excellent in 15 cases, good in 6 cases, fair in 2 cases, and poor in 2 cases at last follow-up; the excellent and good rate was 84%. Conclusion: By the good design of the volar locking plate and the command of surgical techniques, good effectiveness can be achieved in the treatment of senile delayed distal radius fracture.