Girdlestone resection arthroplasty for femoral neck fractures has poorer outcomes than hemiarthroplasty in frail patients with increased risk for arthroplasty-related complications: a retrospective case study of 21 patients.

BACKGROUND AND PURPOSE: Hemiarthroplasty (HA) is the usual treatment for displaced femoral neck fractures (FNF) in elderly patients. Patients may be unsuitable for HA due to secondary conditions such as systemic infections or severe neurological conditions, which is why Girdlestone resection arthroplasty (GRA) may be an option. We aimed to determine (1) patient survival in matched patient groups treated with either GRA or HA and (2) functional outcomes. PATIENTS AND METHODS: 21 patients treated with GRA for FNF in a German university hospital were retrospectively reviewed (2015-2019). After matching for age and comorbidities, a control group of 42 HA patients was established. Patient survival was determined by a Kaplan-Meier analysis. The mean follow-up (FU) was 1.5 (0-4.4) years. Function at FU was documented using the modified Harris Hip Score (mHHS) and the National Hip Fracture Database (NHFD) mobility score. RESULTS: The 1-month-mortality was 19% in the GRA group and 12% in the HA group; the 1-year mortality was 71% and 49%, respectively (P = 0.01). The mHHS at FU was lower in the GRA group than in the HA group (22 [range 0-50] vs. 46 [11-80]). 82% of patients in the GRA group were bedridden post-surgery as opposed to 19% in the HA group. CONCLUSION: Patients with HA after FNF had higher survival and better functional outcomes when compared with GRA in matched patient groups. Considering this, GRA for FNF should be selected restrictively.

The Effect of Waiting for a Primary Total Hip Arthroplasty on the Overall Hip Function and Quality of Life.

BACKGROUND: The primary aim was to determine whether time spent awaiting primary total hip arthroplasty (THA) affects patient-reported outcome measures (PROMs) using the Oxford Hip score, Harris Hip Score, and visual analogue scale (VAS) pain. The secondary aim was to assess whether patients have worsening HRQoL, while awaiting THA using the European Quality of Life Five Dimension (EQ-5D) index and EQ-5D health VAS. METHODS: This was a single center cross-sectional study of 190 patients awaiting THA. Patients were divided into waiting "more than 6 months" and "less than 6 months." Baseline and current scores were compared. Multivariate regression analyses were performed to identify predictors of PROM change. RESULTS: No significant intergroup differences were observed for change in preoperative Oxford Hip score, Harris Hip Score, and VAS pain from index consultation to time of study. The EQ-5D index and EQ-5D health VAS decreased significantly further in patients waiting more than 6 months (P = .043, P = .004). Time awaiting THA was significantly associated with a decrease in EQ-5D index and EQ-5D health VAS in multivariate regression (P = .013, P < .001). CONCLUSIONS: Waiting more than 6 months is not associated with a decrease in hip-specific PROMs and longer waiting times are not associated with changes in hip-specific PROMs. Waiting time was associated with a decrease in health-related quality of life and patients waiting more than 6 months had significantly higher decreases in EQ-5D scores. This suggests that living longer with hip osteoarthritis leads to a decrease in QoL, not necessarily through perceived osteoarthritis progression. LEVEL OF EVIDENCE: Level III cross-sectional study.

Treatment of Severe Acetabular Defects With an Antiprotrusio Cage and Trabecular Metal Augments - Clinical and Radiographic Results After a Mean Follow-Up of 6.6 Years.

BACKGROUND: Large acetabular bone defects present a serious challenge in revision total hip arthroplasty. The off-label use of antiprotrusio cages in combination with tantalum augments is a promising treatment option in these difficult situations. METHODS: Between 2008 and 2013, 100 consecutive patients underwent acetabular cup revision with a cage-augment combination in Paprosky 2 and 3 defect types (including pelvic discontinuities). There were 59 patients available for follow-up. The primary endpoint was the explantation of the cage-and-augment construct. The secondary endpoint was acetabular cup revision for any reason. Also, radiographic and functional outcomes (Western Ontario and McMaster Universities Osteoarthritis Index, Harris Hip Score) were evaluated. Implant survival rates were determined using a Kaplan-Meier analysis. The significance level was set at P < .05. RESULTS: Explantation-free survivorship of the "Cage-and-Augment" system was 91.9% after a mean follow-up of 6.2 years (range, 0 to 12.8). All 6 explantations were due to periprosthetic joint infection (PJI). The overall revision-free implant survival rate was 85.7%, including 6 additional liner revisions due to instability. In addition, 6 early PJI occurred, which were successfully treated with debridement, irrigation, and implant retention. We did observe one patient who had radiographic loosening of the construct without necessity for treatment. CONCLUSION: The combination of an antiprotrusio cage with tantalum augments is a promising technique in treating large acetabular defects. A major risk of PJI and instability due to large bone and soft tissue defects needs special attention.

[Strategies for cup revision]. / Strategien für die Pfannenrevision.

Hip arthroplasty revision management can range from simple procedures using standard implants to complex surgical interventions requiring the combined use of revision cups, metal augments, bone grafts, and antiprotrusio cages. The adequate restoration of biomechanics and function of the hip joint with reconstruction of the original center of rotation can be challenging. We present an overview of various available techniques with the associated implant and anchoring strategies and the respective clinical results depending on the acetabular defect situation.

Ultrasonic bone cement removal efficiency in total joint arthroplasty revision: A computer tomographic-based cadaver study.

Polymethylmethacrylate (PMMA) removal during septic total joint arthroplasty revision is associated with a high fracture and perforation risk. Ultrasonic cement removal is considered a bone-preserving technique. Currently, there is still a lack of sound data on efficacy as it is difficult to detect smaller residues with reasonable technical effort. However, incomplete removal is associated with the risk of biofilm coverage of the residue. Therefore, the study aimed to investigate the efficiency of ultrasonic-based PMMA removal in a human cadaver model. The femoral components of a total hip and a total knee prosthesis were implanted in two cadaver femoral canals by 3rd generation cement fixation technique. Implants were then removed. Cement mantle extraction was performed with the OSCAR-3-System ultrasonic system (Orthofix®). Quantitative analysis of cement residues was carried out with dual-energy and microcomputer tomography. With a 20 µm resolution, in vitro microcomputer tomography visualized tiniest PMMA residues. For clinical use, dual-energy computer tomography tissue decomposition with 0.75 mm resolution is suitable. With ultrasound, more than 99% of PMMA was removed. Seven hundred thirty-four residues with a mean volume of 0.40 ± 4.95 mm3 were identified with only 4 exceeding 1 cm in length in at least one axis. Ultrasonic cement removal of PMMA was almost complete and can therefore be considered a highly effective technique. For the first time, PMMA residues in the sub-millimetre range were detected by computer tomography. Clinical implications of the small remaining PMMA fraction on the eradication rate of periprosthetic joint infection warrants further investigations.

Microbiological pathogen analysis in native versus periprosthetic joint infections: a retrospective study.

BACKGROUND: The presence or absence of an implant has a major impact on the type of joint infection therapy. Thus, the aim of this study was the examination of potential differences in the spectrum of pathogens in patients with periprosthetic joint infections (PJI) as compared to patients with native joint infections (NJI). METHODS: In this retrospective study, we evaluated culture-positive synovial fluid samples of 192 consecutive patients obtained from January 2018 to January 2020 in a tertiary care university hospital. For metrically distributed parameters, Mann-Whitney U was used for comparison between groups. In case of nominal data, crosstabs and Chi-squared tests were implemented. RESULTS: Overall, 132 patients suffered from periprosthetic joint infections and 60 patients had infections of native joints. The most commonly isolated bacteria were coagulase-negative Staphylococci (CNS, 28%), followed by Staphylococcus aureus (S. aureus, 26.7%), and other bacteria, such as Streptococci (26.3%). We observed a significant dependence between the types of bacteria and the presence of a joint replacement (p < 0.05). Accordingly, detections of CNS occurred 2.5-fold more frequently in prosthetic as compared to native joint infections (33.9% vs. 13.4% p < 0.05). In contrast, S. aureus was observed 3.2-fold more often in NJIs as compared to PJIs (52.2% vs. 16.4%, p < 0.05). CONCLUSION: The pathogen spectra of periprosthetic and native joint infections differ considerably. However, CNS and S. aureus are the predominant microorganisms in both, PJIs and NJIs, which may guide antimicrobial therapy until microbiologic specification of the causative pathogen.

Cementation of a dual mobility cup in a well-fixed acetabular component- a reliable option in revision total hip arthroplasty?

BACKGROUND: The "cup-in-cup" technique allows for revision of failed total hip arthroplasty (THA) when the cementless cup is well fixed. Furthermore, it can be used for liner wear or mechanical failure where liner replacement may be impossible or impractical. Recently, the "cup-in-cup" technique in combination with dual mobility cups (DMC) has drawn increased attention. Our aim was to report on the clinical and radiographic outcomes following this surgery. METHODS: From 2015 to 2020, 33 patients treated with the DMC- "cup in cup" technique were retrospectively reviewed. Fourteen patients had died while 19 were available for the final follow-up (FU), of which 15 underwent both a radiograph and a FU visit, 2 underwent a radiograph only and 2 underwent a telephone interview only. Patient-related outcome measures included the HHS and the WOMAC. Radiographs were assessed for implant loosening and positioning. Primary endpoint was revision of any cause and secondary endpoint was loosening of the DMC at the latest FU. The survival analysis was conducted using the Kaplan-Meier method. RESULTS: The mean age at surgery was 78.6 ± 7.1 (63-93) years and the mean surgery duration was 124.4 ± 52.0 (60-245) minutes. Recurrent dislocation (42.4%), periprosthetic fracture (39.4%) and polyethylene wear (6.1%) were the most frequent reasons for surgery. The mean FU duration (n = 19) was 28.5 ± 17.3 (3-64) months. The mean HHS score at FU was 59.4 ± 22.2 (29-91) and the mean WOMAC score was 59.7 ± 25.6 (15.6-93.8). Two cups were revised due to instability and one revision was performed due to periprosthetic joint infection, accounting for an overall cup survival rate of 86.8% after a mean FU of 22.9 ± 18.0 (1.5-64.6) months. The survival rate free of loosening was 90.9% after a mean FU of 22.3 ± 18.5 (1.5-64.7) months. CONCLUSIONS: We found that the cementation of a DMC in a well-fixed cup is a promising short- to mid-term treatment addressing THA instability especially in elderly and frail patients, who benefit from a reduced operation time. Proper cementation technique, adequate cup positioning as well as selection of a sufficiently large DMC are crucial for treatment success. Longer FUs will be needed in the future in order to further prove the benefit of this technique.

Large Soft-tissue Mass Formation After Revision Total Knee Arthroplasty: An Unusual Case of Adverse Reaction to Metal Debris and Review of the Literature.

We report about the rare case of a patient who developed large soft-tissue mass formations related with revision total knee arthroplasty which was implanted 4 years prior. Owing to suspected periprosthetic joint infection, the prosthesis was removed and the lesions were resected, resulting in severe soft-tissue loss and temporary arthrodesis using a poly(methyl methacrylate) spacer. Histological analysis revealed a type VI periprosthetic membrane. The situation was further complicated by wound infection requiring multiple revision surgeries. After discussion and evaluation of the available treatment options, the decision for an above-the-knee amputation was made. The tissue reaction resulting in these soft-tissue lesions is referred to as an "adverse local tissue reaction." Wear-induced lesions after total knee arthroplasty, especially of this magnitude, are very rare and difficult to treat.

Does preoperative antibiotic prophylaxis affect sonication-based diagnosis in implant-associated infection?

As culture-negative implant-associated infection denote a diagnostic challenge, sonicate fluid cultures of the explanted endoprosthesis and osteosynthesis components are frequently used. However, the effect of antibiotic treatment on pathogen detection by sonication fluid cultures in implant-associated infection has not been investigated. Thus, the aim of this study was to evaluate the influence of preoperative antibiotic prophylaxis (PAP) and antibiotic therapy (AT) on sonicate fluid cultures in patients with implant-associated infection. In this retrospective study three groups were compared: (i) standard PAP, (ii) AT for at least one day, and (iii) no antibiotics before surgery. For the inclusion criteria, an established diagnostic protocol for implant-associated infection was used. Sonicate fluid cultures were validated by corresponding microbiological and histopathological samples. In 90 patients with single and multiple infections, 114 pathogens were detected. The detection rate by sonicate fluid cultures in patients receiving PAP (n = 27, 29 pathogens), AT before surgery (n = 33, 48 pathogens) and no antibiotics before surgery (n = 30, 37 pathogens) were 86.2%, 81.3%, and 86.5% (p = .778), respectively. Eleven of 114 infectious agents were detected exclusively by sonicate fluid cultures, while conventional tissue culture failed in these cases. PAP and AT do not affect intraoperative cultures in implant-associated infection. It is therefore not recommended to omit antibiotic prophylaxis in patients with implant-associated infection. Algorithms including both sonicate fluid cultures and tissue samples should be used for appropriate microbiological diagnosis of implant-associated infections.

Plastic-Reconstructive Treatment Algorithm for Dead Space Management Following Septic Total Hip Arthroplasty Removal: AV Loop and Two-Stage Free Myocutaneous Latissimus Dorsi Flap. / Plastisch-rekonstruktiver Behandlungsalgorithmus des Totraummanagements nach septischer Hüft-TEP-Explantation: der AV-Loop und der zweizeitige freie myokutane Latissimus-dorsi-Lappen.

BACKGROUND: A 61-year-old patient presented with a right Girdlestone hip and wound dehiscence due to extensive dead space after radical debridement and septic arthroplasty removal. A two-stage reconstruction with the application of a subcutaneous autologous arterio-venous (AV) loop using an autologous vena saphena magna (VSM) interposition graft followed by a free latissimus dorsi flap was performed. METHOD: We decided to perform a two-stage procedure with AV loop creation in the first step and free flap transplantation seven days after it. In the first step, an AV vascular loop was prepared by transplanting the contralateral VSM interposition graft to the inguinal femoral vessels with subcutaneous passage of the venous loop. In the second step after 7 days, the wound was closed by a two-team approach. One surgical team completed the wound debridement, while the other team harvested the flap by microsurgical preparation of the thoracodorsal pedicle in the right axilla. Upon completed harvest, the flap was placed into the wound to fill the periosseous dead space, and the anastomosis was performed in an end-to-end fashion. RESULT: The patient remained free of infection with a well-healed flap. He was mobilized on crutches with partial weight bearing on the operated leg. A lower extremity prosthesis with pelvic support was customized.

Dnmt3a-Mediated DNA Methylation Changes Regulate Osteogenic Differentiation of hMSCs Cultivated in the 3D Scaffolds under Oxidative Stress.

Oxidative stress (OS) caused by multiple factors occurs after the implantation of bone repair materials. DNA methylation plays an important role in the regulation of osteogenic differentiation. Moreover, recent studies suggest that DNA methyltransferases (Dnmts) are involved in bone formation and resorption. However, the effect and mechanism of DNA methylation changes induced by OS on bone formation after implantation still remain unknown. Three-dimensional (3D) cell culture systems are much closer to the real situation than traditional monolayer cell culture systems in mimicking the in vivo microenvironment. We have developed porous 3D scaffolds composed of mineralized collagen type I, which mimics the composition of the extracellular matrix of human bone. Here, we first established a 3D culture model of human mesenchymal stem cells (hMSCs) seeded in the biomimetic scaffolds using 160 µM H2O2 to simulate the microenvironment of osteogenesis after implantation. Our results showed that decreased methylation levels of ALP and RUNX2 were induced by H2O2 treatment in hMSCs cultivated in the 3D scaffolds. Furthermore, we found that Dnmt3a was significantly downregulated in a porcine anterior lumbar interbody fusion model and was confirmed to be reduced by H2O2 treatment using the 3D in vitro model. The hypomethylation of ALP and RUNX2 induced by H2O2 treatment was abolished by Dnmt3a overexpression. Moreover, our findings demonstrated that the Dnmt inhibitor 5-AZA can enhance osteogenic differentiation of hMSCs under OS, evidenced by the increased expression of ALP and RUNX2 accompanied by the decreased DNA methylation of ALP and RUNX2. Taken together, these results suggest that Dnmt3a-mediated DNA methylation changes regulate osteogenic differentiation and 5-AZA can enhance osteogenic differentiation via the hypomethylation of ALP and RUNX2 under OS. The biomimetic 3D scaffolds combined with 5-AZA and antioxidants may serve as a promising novel strategy to improve osteogenesis after implantation.

Sports Therapy Interventions Following Total Hip Replacement.

BACKGROUND: Sport rehabilitation is a reimbursable intervention assisting reintegration and self-help. In this study, we measured the effects of sport rehabilitation on muscle strength around the hip joint at 1 year after surgery, as well as cardiopulmonary endurance performance and stability of stance, in patients who had undergone a first implantation of a total hip endoprosthesis (total hip replacement, THR) as a treatment for osteoarthritis of the hip. METHODS: 160 patients were randomly allotted either to an intervention group with intensive sport rehabilitation for the first year or to a control group. At three time points (baseline, six and twelve months after surgery), measurements were made of muscular strength around the hip joint (with isokinetic dynamometry), stability of stance, and endurance performance. The primary endpoint was the change in strength of the hip extensors, abductors, flexors, and adductors at twelve months after surgery. RESULTS: With respect to the primary endpoint, the results were not significantly better in patients who had received sport rehabilitation than in those who had not. At one year, the patients in the intervention group had less pain as measured by the WOMAC pain score (p = 0.023), though the size of this effect was small (r = 0.27). Health-related quality of life was higher in the intervention group at six months, albeit with a small effect size (p = 0.036, r = 0.25); this was no longer demonstrable at one year. The other parameters studied displayed no significant changes. CONCLUSION: This trial did not demonstrate any significant benefit of sports rehabilitation on functional outcomes in patients who had undergone total hip replacement. Nonetheless, positive trends after the intervention were seen in some parameters. The unexpectedly high dropout rate had been underestimated in the planning phase of the trial; further trials with larger numbers of patients should be performed.

Two-step stem cell therapy improves bone regeneration compared to concentrated bone marrow therapy.

Adult stem cells are a promising tool to positively influence bone regeneration. Concentrated bone marrow therapy entails isolating osteoprogenitor cells during surgery with, however, only low cells yield. Two step stem cell therapy requires an additional harvesting procedure but generates high numbers of progenitor cells that facilitate osteogenic pre-differentiation. To further improve bone regeneration, stem cell therapy can be combined with growth factors from platelet rich plasma (PRP) or its lysate (PL) to potentially fostering vascularization. The aim of this study was to investigate the effects of bone marrow concentrate (BMC), osteogenic pre-differentiation of mesenchymal stromal cells (MSCs), and PL on bone regeneration and vascularization. Bone marrow from four different healthy human donors was used for either generation of BMC or for isolation of MSCs. Seventy-two mice were randomized to six groups (Control, PL, BMC, BMC + PL, pre-differentiated MSCs, pre-differentiated MSCs + PL). The influence of PL, BMC, and pre-differentiated MSCs was investigated systematically in a 2 mm femoral bone defect model. After a 6-week follow-up, the pre-differentiated MSCs + PL group showed the highest bone volume, highest grade of histological defect healing and highest number of bridged defects with measurable biomechanical stiffness. Using expanded and osteogenically pre-differentiated MSCs for treatment of a critical-size bone defect was favorable with regards to bone regeneration compared to treatment with cells from BMC. The addition of PL alone had no significant influence; therefore the role of PL for bone regeneration remains unclear. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1318-1328, 2019.

Erythropoietin inhibits osteoblast function in myelodysplastic syndromes via the canonical Wnt pathway.

The effects of erythropoietin on osteoblasts and bone formation are controversial. Since patients with myelodysplastic syndromes often display excessively high erythropoietin levels, we aimed to analyze the effect of erythropoietin on osteoblast function in myelodysplastic syndromes and define the role of Wnt signaling in this process. Expression of osteoblast-specific genes and subsequent osteoblast mineralization was increased in mesenchymal stromal cells from healthy young donors by in vitro erythropoietin treatment. However, erythropoietin failed to increase osteoblast mineralization in old healthy donors and in patients with myelodysplasia, whereas the basal differentiation potential of the latter was already significantly reduced compared to that of age-matched controls (P<0.01). This was accompanied by a significantly reduced expression of genes of the canonical Wnt pathway. Treatment of these cells with erythropoietin further inhibited the canonical Wnt pathway. Exposure of murine cells (C2C12) to erythropoietin also produced a dose-dependent inhibition of TCF/LEF promoter activity (maximum at 500 IU/mL, -2.8-fold; P<0.01). The decreased differentiation capacity of erythropoietin-pretreated mesenchymal stromal cells from patients with myelodysplasia could be restored by activating the Wnt pathway using lithium chloride or parathyroid hormone. Its hematopoiesis-supporting capacity was reduced, while reactivation of the canonical Wnt pathway in mesenchymal stromal cells could reverse this effect. Thus, these data demonstrate that erythropoietin modulates components of the osteo-hematopoietic niche in a context-dependent manner being anabolic in young, but catabolic in mature bone cells. Targeting the Wnt pathway in patients with myelodysplastic syndromes may be an appealing strategy to promote the functional capacity of the osteo-hematopoietic niche.

FOXO1-suppressed miR-424 regulates the proliferation and osteogenic differentiation of MSCs by targeting FGF2 under oxidative stress.

Recently, microRNAs (miRNAs) have been identified as key regulators of the proliferation and differentiation of mesenchymal stem cells (MSCs). Our previous in vivo study and other in vitro studies using miRNA microarrays suggest that miR-424 is involved in the regulation of bone formation. However, the role and mechanism of miR-424 in bone formation still remain unknown. Here, we identified that the downregulation of miR-424 mediates bone formation under oxidative stress, and we explored its underlying mechanism. Our results showed that miR-424 was significantly downregulated in an anterior lumbar interbody fusion model of pigs and in a cell model of oxidative stress induced by H2O2. The overexpression of miR-424 inhibited proliferation and osteogenic differentiation shown by a decrease in alkaline phosphatase (ALP) activity, mineralization and osteogenic markers, including RUNX2 and ALP, whereas the knockdown of miR-424 led to the opposite results. Moreover, miR-424 exerts its effects by targeting FGF2. Furthermore, we found that FOXO1 suppressed miR-424 expression and bound to its promoter region. FOXO1 enhanced proliferation and osteogenic differentiation in part through the miR-424/FGF2 pathway. These results indicated that FOXO1-suppressed miR-424 regulates both the proliferation and osteogenic differentiation of MSCs via targeting FGF2, suggesting that miR-424 might be a potential novel therapeutic strategy for promoting bone formation.

Large-scale gene expression profiling data of bone marrow stromal cells from osteoarthritic donors.

This data article contains data related to the research article entitled, "in vitro characterization of bone marrow stromal cells from osteoarthritic donors" [1]. Osteoarthritis (OA) represents the main indication for total joint arthroplasty and is one of the most frequent degenerative joint disorders. However, the exact etiology of OA remains unknown. Bone marrow stromal cells (BMSCs) can be easily isolated from bone marrow aspirates and provide an excellent source of progenitor cells. The data shows the identification of pivotal genes and pathways involved in osteoarthritis by comparing gene expression patterns of BMSCs from osteoarthritic versus healthy donors using an array-based approach.

In vitro characterization of bone marrow stromal cells from osteoarthritic donors.

BMSCs, also known as bone marrow-derived mesenchymal stem cells, provide an excellent source of progenitor cells for regenerative therapy. To assess whether osteoarthritis (OA) affects the regenerative potential of BMSCs we compared the proliferation and differentiation potential as well as the surface marker expression profile of OA- versus control BMSCs. BMSCs were isolated from bone marrow aspirates of n=14 patients with advanced-stage idiopathic hip OA (67±6years) and n=15 healthy individuals (61±4years). Proliferation was quantified by total DNA content and colony-forming-units of fibroblastsmax (CFU-F) assay. Differentiation assays included immunohistology, cell-specific alkaline phosphatase (ALP) activity, and osteogenic, chondrogenic as well as adipogenic marker gene qRT-PCR. Expression of BMSC-associated surface markers was analyzed using flow cytometry. No significant intergroup differences were observed concerning the proliferation potential, cell-specific ALP activity as well as adipogenic and osteogenic differentiation marker gene expressions. Interestingly, SOX9 gene expression levels were significantly increased in OA-BMSCs after 14days of chondrogenic stimulation (p<0.01). The surface markers CD73, CD90 and STRO-1 were elevated in relation to CD14, CD34 and CD45 in both groups (p<0.0001). Notably, OA-BMSCs showed significantly increased CD90 (p<0.01) and decreased CD166 (p<0.001) levels. Overall, the in vitro characteristics of BMSCs are not markedly influenced by OA. However, increased SOX9 and CD90 as well as reduced CD166 expression levels in OA-BMSCs warrant further investigation. These data will help to further understand the role of BMSC in OA and facilitate the application of autologous cell-based strategies for musculoskeletal tissue regeneration in OA patients.

The effect of SDF-1α on low dose BMP-2 mediated bone regeneration by release from heparinized mineralized collagen type I matrix scaffolds in a murine critical size bone defect model.

The treatment of critical size bone defects represents a challenge. The growth factor bone morphogenetic protein 2 (BMP-2) is clinically established but has potentially adverse effects when used at high doses. The aim of this study was to evaluate if stromal derived factor-1 alpha (SDF-1α) and BMP-2 released from heparinized mineralized collagen type I matrix (MCM) scaffolds have a cumulative effect on bone regeneration. MCM scaffolds were functionalized with heparin, loaded with BMP-2 and/or SDF-1α and implanted into a murine critical size femoral bone defect (control group, low dose BMP-2 group, low dose BMP-2 + SDF-1α group, and high dose BMP-2 group). After 6 weeks, both the low dose BMP-2 + SDF-1α group (5.8 ± 0.6 mm³, p = 0.0479) and the high dose BMP-2 group (6.5 ± 0.7 mm³, p = 0.008) had a significantly increased regenerated bone volume compared to the control group (4.2 ± 0.5 mm³). There was a higher healing score in the low dose BMP-2 + SDF-1α group (median grade 8; Q1-Q3 7-9; p = 0.0357) than in the low dose BMP-2 group (7; Q1-Q3 5-9) histologically. This study showed that release of BMP-2 and SDF-1α from heparinized MCM scaffolds allows for the reduction of the applied BMP-2 concentration since SDF-1α seems to enhance the osteoinductive potential of BMP-2. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2126-2134, 2016.