Bone marrow stem cells (BMSCs) represent a collection of different cell types exhibiting stem cell characteristics but with notable heterogeneity. Among these, Skeletal Stem Cells (SSCs) represent a distinct matrix subgroup within BMSC and demonstrate a specialized capacity to facilitate bone formation, recruit chondrocytes, and contribute to hematopoiesis. SSCs play a pivotal role in orchestrating the functions of skeletal organs. Local ischemia has a significant impact on cell survival and function. We hypothesize that bone ischemia induces alterations in the differentiation potential of SSCs, consequently influencing changes in bone structure. We mechanically dissected tissue from the necrotic segment in the femoral head and more normal appearing areas from the femoral neck of specimens from 5 patients diagnosed with osteonecrosis of the femoral head (ONFH). These tissues were enzymatically broken down into individual cell suspensions. Utilizing fluorescence-activated cell sorting (FACS) based on specific surface markers indicative of human skeletal stem cells (hSSC), namely CD45- CD235a- CD31- TIE2- Podoplanin (PDPN)+ CD146- CD73+ CD164+, we isolated a distinct cell population. Subsequent in vitro evaluations, focusing on clonogenicity, osteogenesis, and chondrogenesis were conducted to assess the functional prowess of these SSCs. Moreover, we introduced BMP2 at a concentration of 50ng/ml to SSCs extracted from necrotic regions to potentially reinstate their osteogenic capabilities. We effectively isolated SSCs from both Necrotic and Non-necrotic Zones. We observed an augmented clonal formation capacity and chondrogenesis ability of SSCs isolated from the necrotic region, accompanied by a significant decline in osteogenic ability (P＜0.01), an effect not reversible even with the addition of BMP2. Ischemia adversely affects the proliferation and function of SSCs, resulting in a diminished osteogenic capacity and an insensitivity to BMP2, ultimately leading to structural alterations in bone tissue

Introduction. In early stage osteonecrosis of the femoral head (ONFH), core decompression (CD) is often performed; however, approximately 30% of CD cases progress to femoral head collapse. Bone healing can be augmented by preconditioning MSCs (pMSCs) with inflammatory cytokines. Another immunomodulatory approach is the timely resolution of inflammation using cytokines such as IL-4. We investigated the efficacy of pMSC and genetically modified MSCs that over-express IL-4 (IL4-MSCs) on steroid-associated ONFH in rabbits. Methods. Thirty-six male skeletally mature NZW rabbits received methylprednisolone acetate (20mg/kg) IM once 4 weeks before surgery. There were 6 groups:. CD alone – a 3 mm drill hole. + injection into the CD of:. hydrogel (HG) - 200 μl of hydrogel carrier. MSCs–1 million rabbit MSCs. pMSC - LPS (20 μg/ml) + TNFα (20 ng/ml) preconditioned MSCs. IL4-MSCs – rabbit IL-4 over-expressing MSCs. IL4-pMSCs – preconditioned IL-4 over-expressing MSCs. Eight weeks after surgery, femurs were harvested, and evaluated by microCT, biomechanical, and histological analyses. Results. Bone mineral density (BMD) and bone volume fraction (BVF) increased in the pMSC group compared to the CD and MSC groups . outside. of the CD area (p < 0.05, Fig.1). Similarly, the IL4-pMSC group was increased compared to the CD group (p < 0.05). The percentage of empty lacunae in the IL4-MSC group was significantly less than other groups . outside. the CD area (p < 0.05, Fig.2); however, IL4-MSC group had less trabecular bone formation . inside. the CD. The mechanical tests demonstrated no differences. Discussion. This rabbit steroid-associated ONFH model demonstrated that pMSC increased new bone formation after CD; IL4-MSCs that continuously secreted IL-4 decreased the number of empty lacunae . Immunomodulation of bone healing has the potential to improve bone healing after CD for early stage ONFH; these interventions must be applied in a temporally sensitive fashion. For any figures, tables, or references, please contact the authors directly

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To investigate the extent of bone development around the scaffold of custom triflange acetabular components (CTACs) over time.

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Large acetabular bone defects encountered in revision total hip arthroplasty (THA) are challenging to restore. Metal constructs for structural support are combined with bone graft materials for restoration. Autograft is restricted due to limited volume, and allogenic grafts have downsides including cost, availability, and operative processing. Bone graft substitutes (BGS) are an attractive alternative if they can demonstrate positive remodelling. One potential product is a biphasic injectable mixture (Cerament) that combines a fast-resorbing material (calcium sulphate) with the highly osteoconductive material hydroxyapatite. This study reviews the application of this biomaterial in large acetabular defects.

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This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model.

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Developmental dysplasia of the hip (DDH) describes a pathological relationship between the femoral head and acetabulum. Periacetabular osteotomy (PAO) may be used to treat this condition. The aim of this study was to evaluate the results of PAO in adolescents and adults with persistent DDH.

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One-stage revision hip arthroplasty for periprosthetic joint infection (PJI) has several advantages; however, resection of the proximal femur might be necessary to achieve higher success rates. We investigated the risk factors for resection and re-revisions, and assessed complications and subsequent re-revisions.

Background. Heterotopic ossification (HO) is lamellar bone formation in the soft tissues following trauma or joint replacement for osteoarthritis (OA). A genome wide association study of HO patients after total hip arthroplasty for OA has identified Kinesin Family Member 26B (KIF26B) as a gene associated with HO severity. KIF26B has previously been associated with HO in mice. Hypothesis and aims: We hypothesised that Kif26b regulates the osteogenic trans-differentiation of myoblasts; a possible mechanism of HO. Using an in vitro model, we wished to establish whether Kif26b is involved in HO formation and to explore the molecular mechanism. Methods. We developed CRISPR/Cas9 mediated Kif26b knockout (KO) C2C12 myoblasts. Wild type (WT) and KO cells were transdifferentiated towards an osteogenic lineage using BMP-2 for 24 days. The effect of Kif26b KO on mineralisation was quantified by calcium staining. The mean difference (±SEM) in gene expression between WT and KO lines was compared with ANOVA. Results. qPCR and western blotting confirmed Kif26b knockout. Kif26b deficient cells produced substantially less mineral versus WT in response to BMP-2 (34.71% ±3.62%, n=12, P<0.0001). At day 8 of osteogenic differentiation, loss of Kif26b abrogated Osterix (113.6 ±6.781 n=5, P<0.0001), Osteocalcin (737.9 ±84.25, n=5, P<0.0001) and Alkaline phosphatase (6989 ±365.7, n=5, P<0.0001) expression, and down regulated Runx2 (2.725 ±0.7724, n=5, P<0.0052) and Collagen type I (7.25 ±1.154, n=5, P<0.0001) expression relative to WT. The knockout cells also appeared morphologically different. Compared to WT, the Kif26b KO cells displayed a less osteoblast-like morphology during transdifferentiation. Conclusion. Our findings demonstrate an undescribed function for Kif26b as a critical regulator of pathological ossification, with a putative role in HO pathogenesis after THA

We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p = 0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement

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Bone marrow-derived mesenchymal stem cells obtained from bone marrow aspirate concentrate (BMAC) with platelet-rich plasma (PRP), has been used as an adjuvant to hip decompression. Early results have shown promise for hip preservation in patients with osteonecrosis (ON) of the femoral head. The purpose of the current study is to examine the mid-term outcome of this treatment in patients with precollapse corticosteroid-induced ON of the femoral head.

We describe the survival of 134 consecutive JRI Furlong hydroxyapatite-coated uncemented total hip replacements. The mean follow-up was for 14.2 years (13 to 15). Patients were assessed clinically, using the Merle d’Aubigné and Postel score. Radiographs were evaluated using Gruen zones for the stem and DeLee and Charnley zones for the cup. Signs of subsidence, radiolucent lines, endosteal bone formation (spot welds) and pedestal formation were used to assess fixation and stability of the stem according to Engh’s criteria. Cup angle, migration and radiolucency were used to assess loosening of the cup. The criteria for failure were revision, or impending revision because of pain or loosening. Survival analysis was performed using a life table and the Kaplan-Meier curve. The mean total Merle d’Aubigné and Postel score was 7.4 pre-operatively and 15.9 at follow-up. During the study period 22 patients died and six were lost to follow-up. None of the cups was revised. One stem was revised for a periprosthetic fracture following a fall but none was revised for loosening, giving a 99% survival at 13 years. Our findings suggest that the long-term results of these hydroxyapatite-coated prostheses are more than satisfactory

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Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4^-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue.

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We aimed to evaluate the long-term outcome of highly cross-linked polyethylene (HXLPE) cemented acetabular components and assess whether any radiolucent lines (RLLs) which arose were progressive.

Bone ingrowth is desired with uncemented hip implants. Infection is clearly undesirable. We have worked on developing a nanofiber coating for implants that would enhance bone formation while inhibiting infection. Few studies have focused on developing an implant surface nanofiber (NF) coating to prevent infection and enhance osseointegration by local drug release. In this study, coaxial doxycycline (Doxy)-doped polycaprolactone/polyvinyl alcohol (PCL/PVA) Nanofibers were directly deposited on the titanium (Ti) implant surface during electrospinning. The interaction of loaded Doxy with both PVA and PCL NFs was characterized by Raman spectroscopy. The bonding strength of Doxy-doped NF coating on Ti implants was confirmed by a stand single-pass scratch test. The improved implant osseointegration by PCL/PVA NF coatings in vivo was confirmed by scanning electron microscopy, histomorphometry and micro computed tomography at 2, 4 and 8 weeks after implantation. The bone contact surface (%) changes of NF coating group (80%) is significantly higher than that of no NF group (< 5%, p<0.05). Finally, we demonstrated that Doxy-doped NF coating effectively inhibited bacterial infection and enhanced osseointegration in an infected (Staphylococcus aureus) tibia implantation rat model. Doxy released from NF coating inhibited bacterial growth up to 8 weeks in vivo. The maximal push-in force of Doxy-NF coating (38 N) is much higher than that of NF coating group (6.5 N) 8 weeks after implantation (p<0.05), which was further confirmed by quantitative histological analysis and micro computed tomography. These findings indicate that coaxial PCL/PVA NF coating doped with Doxy and/or other drugs have great potential in enhancing implant osseointegration and preventing infection

The Alloclassic and Endoplus femoral stems have the same grit-blasted surface and are hot forged from the same titanium alloy. Only the external form of the implants differs slightly. It was our aim to examine the differences in radiographic bone response between the Alloclassic (second generation) and the Endoplus (third generation) femoral stems. We compared 79 prostheses in 70 matched patients studied over a minimum of two years. Radiolucent lines, adaptive bone remodelling, subsidence, heterotopic bone formation and lysis were recorded in the Gruen zones. Radiolucencies were mainly found in zones 1 and 7 but to a greater extent in the Endoplus than in the Alloclassic group (p < 0.001 in zone 1, p < 0.05 in zone 7). We found lucent lines in three or more Gruen zones in seven patients all of whom were in the Endoplus group (p < 0.05). Zones 2 and 6 had a significantly higher rate of lucencies in the Endoplus group (p < 0.001). We encountered a combination of proximal lucent lines in zones 1 and 7 with distal hypertrophy of the cortical bone in zones 2, 3, 5 and 6 in eight patients, all from the Endoplus group (p < 0.05). In other patients bone atrophy (stress shielding) in zones 2 and 6 was seen more frequently in the Endoplus than in the Alloclassic group (p < 0.001). In neither group was there radiological evidence of osteolysis. Heterotopic bone formation and subsidence occurred with similar frequency in both groups. Our study shows that a small change in the form of the femoral implant can result in statistically significant radiological changes in bone remodelling. Whether this will result in clinical compromise is unknown. However, it seems likely that the Endoplus femoral stem will perform differently from the Alloclassic

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The main advantage of 3D-printed, off-the-shelf acetabular implants is the potential to promote enhanced bony fixation due to their controllable porous structure. In this study we investigated the extent of osseointegration in retrieved 3D-printed acetabular implants.

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Bone stock restoration of acetabular bone defects using impaction bone grafting (IBG) in total hip arthroplasty may facilitate future re-revision in the event of failure of the reconstruction. We hypothesized that the acetabular bone defect during re-revision surgery after IBG was smaller than during the previous revision surgery. The clinical and radiological results of re-revisions with repeated use of IBG were also analyzed.

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Femoral revision component subsidence has been identified as predicting early failure in revision hip surgery. This comparative cohort study assessed the potential risk factors of subsidence in two commonly used femoral implant designs.

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The purpose of this study was to evaluate the biological fixation of a 3D printed porous implant, with and without different hydroxyapatite (HA) coatings, in a canine model.

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This single-centre observational study aimed to describe the results of extensive bone impaction grafting of the whole acetabular cavity in combination with an uncemented component in acetabular revisions performed in a standardized manner since 1993.