Introduction. Bone tissue engineering approaches are an emerging strategy to treat bone defects, and commonly involve the delivery of osteogenic cells and/or drugs via a porous scaffold. We have been exploring an alternative injectable approach for drug delivery that would obviate the need for invasive surgery. Hypothesis. Sucrose Acetate Isobutyrate (SAIB) is a sucrose-based ester that is a highly viscous semi-solid. Diluting SAIB with 10–20% ethanol markedly reduces its viscosity, with ethanol diffusing rapidly after in vivo injection. This phase transitioning property makes SAIB an ideal candidate for bone tissue engineering. Materials and methods. The capacity of SAIB to act as a delivery system for recombinant human BMP-2 (rhBMP-2) was tested in a mouse ectopic bone formation model. In this model SAIB was used to deliver 0 to 10μg rhBMP-2. Next, SAIB was compared with porous collagen scaffold used clinically to delivery rhBMP-2 in a head-to-head trial. Commercial SAIB and SAIB produced in-house were also compared. Bone volumes were quantified by μCT. Discussion. Bone was found to form with as little as 2μg rhBMP-2 when delivered with SAIB. Injected SAIB also showed minimal inflammatory response and rapid breakdown, with bone formation occurring between one and two weeks. Conclusion. SAIB was found to be an effective delivery system for rhBMP-2 with translational utility. Future work will be required to examine the upscaling of this delivery system

Purpose. to evaluate the kinematics of a knee with a polyurethane meniscal scaffold for partial meniscus defect substitution during flexion under weightbearing conditions in an upright MRI. In addition, radial displacement and the surface of the scaffold was compared to the normal meniscus. Materials and Methods. One cadaver with a normal lateral meniscus and medial scaffold in the left knee and with a normal medial meniscus and lateral scaffold in the right knee. The scaffolds were implanted to substitute a 3 cm meniscus defect in the posterior horn. The cadaver was scanned in an 0,7T open MRI with a range of motion from 0-30-60-90 to hyperflexion. Kinematics were evaluated on sagittal images by the following two parameters: the position of the femoral condyle, identified by the centre of its posterior circular surface, which is named the flexion facet centre (FFC), and the point of closest approximation between the femoral and tibial subchondral plates, the contact point (CP). Both were identified in relation to the posterior tibial cortex. The displacement, measured on coronal images, is defined as the distance between the tibial plateau and the outer edge of the meniscus. The surface was also measured on coronal slices and contains the triangular surface of the meniscus. Results. Medially from 0 degrees to hyperflexion the FFC does not move anteroposteriorly. Laterally the FFC moves 12 mm backwards. The CP moves 15 mm backwards both lateral and medial. The lateral femoral condyle does roll-back with flexion but the medial does not, so the femur rotates externally around a medial centre. By contrast, both medial and lateral contact points move back, roughly in parallel, from 0 degrees to hyperflexion. The kinematics of the involved compartment is not influenced by the presence of the scaffold compared to the controlateral normal compartment. The radial displacement remains stable during full flexion: both the normal and scaffold meniscus have no different (p > 0,05) position. Both for the normal and the scaffold meniscus there is no difference (p > 0,05) in surface; there is no compression of the meniscus during flexion. Conclusion. The polyurethane implant, indicated for partial meniscus defect substitution, has no effect on the normal kinematics of the knee. Additionally, the degree of flexion has no effect on the external displacement, the surface and compressibility of both the implanted scaffold and the meniscus

Introduction

The therapeutic potential of hematopoietic stem cells for fracture healing has been demonstrated with mechanistic insight of vasculogenesis and osteogenesis enhancement. Lnk has recently been proved an essential inhibitory signaling molecule in SCF-c-Kit signaling pathway for stem cell self-renewal demonstrating enhanced hematopoietic and osteogenic reconstitution in Lnk-deficient mice. We investigated the hypothesis that down regulation of Lnk enhances regenerative response via vasculogenesis and osteogenesis in fracture healing.

As arthroplasty demand grows worldwide, the need for a novel cost-effective treatment option for articular cartilage (AC) defects tailored to individual patients has never been greater. 3D bioprinting can deposit patient cells and other biomaterials in user-defined patterns to build tissue constructs from the “bottom-up,” potentially offering a new treatment for AC defects. Novel composite bioinks were created by mixing different ratios of methacrylated alginate (AlgMA) with methacrylated gelatin (GelMA) and collagen. Chondrocytes and mesenchymal stem cells (MSCs) were then encapsulated in the bioinks and 3D bioprinted using a custom-built extrusion bioprinter. UV and double-ionic (BaCl2 and CaCl2) crosslinking was deployed following bioprinting to strengthen bioink stability in culture. Chondrocyte and MSC spheroids were also bioprinted to accelerate cell growth and development of ECM in bioprinted constructs. Excellent viability of chondrocytes and MSCs was seen following bioprinting (>95%) and maintained in culture, with accelerated cell growth seen with inclusion of cell spheroids in bioinks (p<0.05). Bioprinted 10mm diameter constructs maintained shape in culture over 28 days, whilst construct degradation rates and mechanical properties were improved with addition of AlgMA (p<0.05). Composite bioinks were also injected into in vitro osteochondral defects and crosslinked in situ, with maintained cell viability and repair of osteochondral defects seen over a 14-day period. In conclusion, we developed novel composite bioinks that can be triple-crosslinked, facilitating successful chondrocyte and MSC growth in 3D bioprinted scaffolds and in vitro repair of an osteochondral defect model. This offers hope for a new approach to treating AC defects

Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. The need for a novel, cost effective treatment option for osteochondral defects has therefore never been greater. As an emerging technology, three-dimensional (3D) bioprinting has the capacity to deposit cells, extracellular matrices and other biological materials in user-defined patterns to build complex tissue constructs from the “bottom up”. Through use of extrusion bioprinting and fused deposition modelling (FDM) 3D printing, porous 3D scaffolds were successfully created in this study from hydrogels and synthetic polymers. Mesenchymal stem cells (MSCs) seeded onto polycaprolactone scaffolds with defined pore sizes and porosity maintained viability over a 7-day period, with addition of alginate hydrogel and scaffold surface treatment with NaOH increasing cell adhesion and viability. MSC-laden alginate constructs produced via extrusion bioprinting also maintained structural integrity and cell viability over 7 days in vitro culture. Growth within osteogenic media resulted in successful osteogenic differentiation of MSCs within scaffolds compared to controls (p<0.001). MSC spheroids were also successfully created and bioprinted within a novel, supramolecular hydrogel with tunable stiffness. In conclusion, 3D constructs capable of supporting osteogenic differentiation of MSCs were biofabricated via FDM and extrusion bioprinting. Future work will look to increase osteochondral construct size and complexity, whilst maintaining cell viability

Osteoinductive bone substitutes are in their developmental infancy and a paucity of effective grafts options persists despite clinical demand. Bone mineral substitutes such as hydroxyapatite cause minimal biological activity when compared to osteoinductive systems present biological growth factors in order to drive bone regeneration. We have previously demonstrated the in-vitro efficacy of a bioengineered system at presenting growth factors at ultra low-doses. This study aimed to translate this growth factor delivery system towards a clinically applicable implant. Osteoinductive surfaces were engineered using plasma polymerisation of poly(ethyl acrylate) onto base materials followed by adsorption of fibronectin protein and subsequently growth factor (BMP-2). Biological activity following ethylene oxide (EO) sterilisation was evaluated using ELISAs targeted against BMP-2, cell differentiation studies and atomic force microscopy. Scaffolds were 3D printed using polycaprolactone/hydroxyapatite composites and mechanically tested using a linear compression models to calculate stress/strain. In-vivo analysis was performed using a critical defect model in 23 mice over an 8 week period. Bone formation was assessed using microCT and histological analysis. Finally, a computer modelling process was developed to convert patient CT images into surface models, then formatted into 3D-printable scaffolds to fill critical defects. Following EO sterilisation, there was no change in scaffold surface and persistent availability of growth factors. Scaffolds showed adequate porosity for cell migration with mechanical stiffness similar to cancellous bone. Finally, the in vivo murine model demonstrated rapid bone formation with evidence of trabecular remodelling in samples presenting growth factors compared to controls

Engineered bone tissue to recreate the continuity of damaged skeletal segments is one of the field of interest of tissue engineering. Trabecular titanium has very good mechanical properties and high in vitro and in vivo biocompatibility: it can be used in biomedical applications to promote osteointegration demonstrating that it can be successfully used for regenerative medicine in orthopaedic surgery (1). Purpose of this investigation was to evaluate the behavior of adipose tissue derived stem cells (hASCs) cultured on scaffolds of Trabecular TitaniumTM (Lima-Lto) (TT). hASCs are considered to be multipotent mesenchymal stem cells that are easily induced to differentiate into functional osteoblasts both in vitro and in vivo (2). The hASCs were obtained from the subcutaneous adipose tissue of healthy donors during total hip replacement procedures after digestion with collagenase. They were seeded on monolayer and on the TT scaffolds, and incubated at 37 degrees C in 5% CO2 with osteogenic medium or control medium. The expression of bone-related genes using RT-PCR, time course of alkaline phosphatase activity and morphological investigation with Scanning Electron Microscopy (SEM) were performed to evaluate the osteogenic differentiation of hASCs. Alkaline phosphatase activity, marker of the differentiation toward the osteogenic pattern, was significantly higher in hASCs grown with osteogenic medium than in cells grown with control medium, both in monolayer and TT scaffolds; moreover, also alkaline phosphatase of hASCs grown on TT scaffolds in the presence of control medium increased with time, differently from that of cells grown on monolayer. The osteogenic differentiated hASCs expressed the bone-related genes type I collagen, osteocalcin, Runx-2 and alkaline phosphatase. SEM observations showed that hASCs differentiated toward osteoblast-like cells: they produced a big amount of extracellular matrix that covered the surface of the porous scaffolds with bridges between the pore walls. These data suggest that hASCs are able to adhere to TT scaffolds, to acquire an osteoblastic phenotype and to produce abundant extracellular matrix, with but also without osteogenic medium. We can therefore conclude that this material carries osteinductive properties being responsible of ostegenic differentiation; consequently, this scaffold/cells construct is effective to regenerate damaged tissue and to restore the function of bone tissue

Introduction. The concept of “bone graft expanders” has been popularised to increase the volume and biological activity of the implanted Material. HYPOTHESIS. Orthoss® granules support exogenously seeded MSCs and attract neighbouring host MSCs. Methods. In 3-D cultures’ Orthoss® granules were seeded with 2×10. 5. bone marrow MSCs/granule and maintained in MSC expansion or differentiation media for 21 days. In homing experiments’ bone autografts were placed in close proximity to Orthoss®. Scaffold colonisation and MSC differentiation were assessed by confocal microscopy’ standard electron microscopy’ and energy-dispersive X-ray spectroscopy. Results. Long-term incubation of MSC/scaffold resulted in formation of multiple cell-matrix layers lining the scaffold pores as well as outer surfaces. MSC differentiation to osteoblasts was evident as strong deposition of Calcium and Phosphorus was detected in both MSC expansion and osteogenic conditions. Cell egress experiments demonstrated the migration of cells from neighbouring autografts and their attachment and re-settlement on Orthoss®. Discussion & Conclusions. Orthoss® scaffolds support MSC attachment’ growth and osteogenic differentiation whereas resident bone subpopulations can rapidly migrate towards’ attach’ and expand on them. These results indicate that Orthoss® can serve as a graft expander for repairing large bone defects in trauma patients

Reconstruction of 10mm segmental bone defects in rat by mesenchymal stem cell derived chondrogenic cells (MSC-DC). Background. Mesenchymal stem cell derived condrogenic cells (MSC-DC) have excellent potential for healing 5 mm bone defect in rat femur. Purpose. To evaluate the effectiveness of MSC-DC on bone healing in 10 mm segmental bone defects in rat femur. Methods. 10 millimeter bone defects were produced in rat femur and fixed with external fixator. We divided this model into four groups according to the kind of graft for bone defects. These bone defects were grafted by MSC-DC seeded on a poly (DL-lactic acid-co-glycolic acid) (PLGA) scaffold in Group A, MSC seeded on a PLGA scaffold in Group B, PLGA scaffold only in Group C, and autologus bone graft in Group D. The healing processes were monitored radiographically and studied biomechanically and histologically. Results. All the bone defects in Group A healed radiographically with bridging callus formation at 4 weeks after the procedure, while none of Group B, C, and D had achieved bone union even at 8 weeks. Mechanical testing revealed that Group A showed approximately 40 % bending strength at 4 weeks compared with the contralateral side, and approximately 60 % at 8 weeks. In histology, Group A, maturation of bridging callus occurred from outside and enchondral ossification was prominent from inside. Conclusion. This study showed that MSC-DC with PLGA scaffold enhances bone healing even in large bone defects

Purpose. The purpose of this study was to evaluate the effects of implantation of mesenchymal stem cell derived condrogenic cells (MSC-DC) on bone healing in segmental defects in rat femur. Methods. Five-millimeter segmental bone defects were produced in the mid-shaft of the femur of Fisher 344 rats and stabilized with external fixator. The Treatment Group received MSC-DC, seeded on a PLGA scaffold, locally at the site of the bone defect, and Control Group received scaffold only. The healing processes were monitored radiographically (Softex), and studied radiographically (Micro-CT) and histologically. Results. All the bone defects in the Treatment Group healed radiographically with bridging callus formation at 4 weeks after the procedure, while none of the Control Group had achieved bone union. Micro-CT showed that newly formed bone volume in the Treatment Group at 16 weeks was 1.5 times that of unaffected side. Histological examination showed that the implanted scaffold of the Treatment Group were covered with periosteum-derived bridging callus and filled with cancellous bone-like tissue derived from enchondral ossification. Conclusion. The results of this study suggest that implantation of MSC-DC surprisingly enhances bone healing in segmental bone defects in rat much better than previously reported similar therapy using MSC

Introduction. The combined incubation of a composite scaffold with bone marrow stromal cells in a perfusion bioreactor could make up a novel hybrid graft material with optimal properties for early fixation of implant to bone. The aim of this study was to create a bioreactor activated graft (BAG) material, which could induce early implant fixation similar to that of allograft. Two porous scaffold materials incubated with cells in a perfusion bioreactor were tested in this study. Methods and Materials. Two groups of 8 skeletally mature female sheep were anaesthetized before aspiration of bone marrow from the iliac crest. For both groups, mononuclear cells were isolated, and injected into a perfusion bioreactor (Millenium Biologix AG, Switzerland). Scaffold granules Ø∼900–1500 μm, ∼88% porosity) in group 1, consisted of hydroxyapatite (HA, 70%) with -tricalcium-phosphate (−TCP, 30%) (Danish Technological Institute, Denmark). The granules were coated with poly-lactic acid (PLA) 12%, in order to increase the mechanical strength of the material (Phusis, France). Scaffold granules Ø∼900–1400 μm, 80% porosity) in group 2 consisted of pure HA/-TCP (Fin Ceramica, Italy). For both groups, cells were incubated in the bioreactor for 2 weeks. Fresh culture medium supplemented with dexamethasone and ascorbic-acid was added every third or fourth day. Porous titanium alloy implants with diameter=length=10mm (Biomet, USA) were inserted bilaterally in each of the distal femurs of the sheep; thus 4 implants in each sheep. The concentric gap (2 mm) surrounding the implant was filled with 1) BAG (autogenous), 2) granules, 3) granules+bone marrow aspirate (BMA, autologous) or 4) allograft. The sheep were euthanized after 6 weeks. Distal femurs were removed and implant-bone samples were divided in two parts. The superficial part was used for mechanical testing and micro-CT scanning, and the profound part for histomorphometry. Push-out tests were performed on an 858 Bionix MTS hydraulic materials testing machine. Shear mechanical properties between implant and newly generated bone were calculated to assess implant fixation. Results were assessed by One-way ANOVA. P-values less than 0.05 were considered significant. Results. One sheep in group 1 had to be euthanized after 4 weeks (excluded). One implant in each group was loosened and could not undergo push-out test (excluded). Group 1: No significant differences regarding failure energy (kJ/m2, p=0.44) or ultimate shear strength (MPa, p=0.17) could be seen. Shear stiffness (MPa) was significantly higher for the allograft group (p=0.04). Group 2: No significant differences regarding failure energy (p=0.11) or shear stiffness (p=0.52) could be seen. Ultimate shear strength was significantly higher for allograft (p=0.04). Results from μ-CT scanning and histomorphometry are pending. Discussion and Conclusion. The present study shows a possible effect of bioreactor activated bone substitute on early implant fixation. We are currently working on bone microarchitecture surrounding implant and histomorphometry. These results will aid in determining if BAG could make up a promising alternative for allograft as bone graft material

Aims

Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections.

Aim. The present study was designed to evaluate the implantation of alginate beads containing human mature allogenic chondrocytes for the treatment of symptomatic cartilage defects in the knee. Methods. A biodegradable, alginate-based biocompatible scaffold containing human mature allogenic chondrocytes was used for the treatment of chondral and osteochondral lesions in the knee. Twenty-one patients were clinically prospectively evaluated with use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and a Visual Analogue Scale (VAS) for pain preoperatively and at 3, 6, 9, 12, 24 and 36 months of follow-up. Results. A statistically significant clinical improvement became apparent after 6 months and patients continued to improve during the 36 months of follow-up. Adverse reactions to the alginate/fibrin matrix seeded with the allogenic cartilage cells were not observed. Two of the procedures failed. One of the patients had loosening of the periosteal flap, which was attributed to a failure of the surgical procedure. The other failure case was the result of the poor quality and quantity of the repair tissue itself. Discussion. The results of this pilot study show that the alginate-based scaffold containing human mature allogenic chondrocytes is feasible for the treatment of symptomatic cartilage defects in the knee. The described technique provides clinical outcomes equal to those of other cartilage repair techniques

Osteocondritis dissecans (OCD) is a relatively common cause of knee pain. Ideal treatment is still controversial. Aim of this exhibit is to describe the outcomes of 5 different surgical techniques in a series of 63 patients. 63patients (age 22.5±7.4 years) affected by OCD of the femoral condyle (45 medial and 17 lateral) were treated by either osteochondral autologous transplantation, autologous chondrocyte implantation with bone graft, biomimetic nanostructured osteochondral scaffold (Maioregen) implantation, bone-cartilage paste graft or bone marrow derived cells transplantation “one-step” technique. Patient evaluation included IKDC score, eq-vas score, X-Rays and MRI preoperatively and at follow-up. Global mean IKDC improved from pre-operative 40.1±14.6 to 77.2±21.3 (p<0.0005) at mean 5.3±4.7 years follow-up, while eq-vas improved from 51.7±17.0 to 83.5±18.3(p<0.0005). No influence of age, size of the lesion, length of follow-up and associated surgeries on the result was found. No differences were found between the results obtained with different surgeries except a slight tendency of better improvement in the result following autologous chondrocyte implantation (p<0.01). Control MRI evidenced a satisfactory repair of cartilaginous layer and subchondral bone. The techniques described were effective in providing good clinical and radiographic results in the treatment of OCD and confirmed the validity of autologous chondrocyte implantation over time. Newer techniques such as Maioregen implantation and “one-step” base on different rationales, the first relying on the characteristics of the scaffold and the second on the regenerative potential of mesenchymal cells. Both of them have the advantages to be minimally invasive surgeries and to require a single operation

Aims

The purpose of this study was to: review the efficacy of the induced membrane technique (IMT), also known as the Masquelet technique; and investigate the relationship between patient factors and technique variations on the outcomes of the IMT.

Introduction. Nonunion is a common and costly fracture outcome. Intricate reciprocity between angiogenesis and osteogenesis means vascular cell-based therapy offers a novel approach to stimulating bone regeneration. Hypothesis. The current study compared early and late outgrowth endothelial progenitor cell subtypes (EPCs vs OECs) for fracture healing potential in vitro and in vivo. Methods. Primary cell cultures were isolated and characterized by endothelial assays, immunosorbent assays, and multi-color flow cytometry. Co-cultures of EPC subtypes with/without primary osteoblasts (pObs) were analyzed for tube length and connectivity. In vivo, EPCs or OECs (1×10. 6. ) seeded on a gelfoam scaffold were implanted in a rat model of nonunion. Radiography was used to monitor callus formation. Results. OECs expressed more BMP-2 and less VEGF than EPCs (p<0.05). Analysis of surface markers showed decreased CD34+/CD133+/Flk-1+, CD133+ and CD45+ populations in OECs while CD34+/CD31+/Flk-1+ cells increased. pObs significantly inhibited the strong tubulogenesis of OECs while enhancing connectivity and sprout length of EPCs. In vivo, 0/6 scaffold-control and 1/5 OEC rats achieved union at 10 weeks. In comparison, all EPC rats achieved full or partial union. Discussion and Conclusion. Despite favorable tubulogenic and osteoconductive profiles of OECs, EPCs display enhanced fracture healing in vivo. Differences in CXCR4 expression and cell-mediated effects may contribute to this result

Purpouse. We hypothesized that patients receiving a medial collagen meniscus implant (MCMI) would show better clinical, radiograpich and Magnetic Resonanace Imaging (MRI) outcomes than patients treated with partial medial meniscectomy (PMM) at minimum 10 year FU. Material and Methods. Thirty-three non-randomized patients (males, mean age 40 years) were enrolled in the study to receive a MCMI (17 patients) or as control treated with a PMM (16 patients). All of them were clinically evaluated at time zero, 5 and minimum 10 years after surgery (mean FU 133 months, range 120–145) by Lysholm, VAS for pain, objective IKDC knee form and Tegner activity level. SF-36 score was performed pre-operatively and at final FU. Bilateral weight-bearing XRays were executed at time zero and at final FU. Minimum 10 years FU MRI images were compared with collected pre-operative MRI images by means of Yulish score. Genovese score was also used to evalute MCMI MRI survivorship. Results. MCMI group showed significantly lower VAS for pain (p = 0.0091), higher objective IKDC (p = 0.0026), Teger index (p = 0.0259) and SF-36 (p = 0.0259 for PHI and p = 0.0036 for MHI) scores compared with PMM group at minimum 10 year FU. Radiographic evaluation showed a significantly lower medial joint line height (p = 0.0002) and side-to-side difference (p = 0.0003) narrowing in MCMI group respect to PMM group at final FU. Discussion. Improvements in pain relief, activity level, objective IKDC score and joint-line preservation are detectable with the use of MCMI at a minimum 10 year FU. On the authors knowledge this is the first long-term controlled trial regarding this device, and our findings confirmed the mid-term good results achieved by Rodkey et al (1). Conclusions. This data support the use of meniscal scaffolds to treat irreparable partial meniscal lesions. Long-term prospective randomized controlled trials on a larger population are necessary to determine the extent and duration of the benefits observed

Objective. To provide a best estimate of the average treatment effect when microfracture was chosen as the intervention of choice in patients with full-thickness cartilage defects of the knee. Design. We focussed on controlled studies which either referred to microfracture alone or in comparison with any other surgical treatment of articular cartilage of the knee. Papers including patients who had been treated by microfracture and concomitant adjuvant procedures like ACL reconstruction or meniscus repair were accepted too, whereas papers reporting on the microfracture technique combined with the implantation of a scaffold were excluded. To achieve a best estimate of the average, to be expected treatment effect we pooled pooled before–after data of study arms using microfracture. Because cartilage studies employ various scales to measure functional improvements, we standardized treatment effects using Hedges' g. To provide clinically meaningful estimates we converted the pooled summary effect back into the respective scales by multiplying the pooled effect with pooled standard deviations of each included clinical scale. Results. A systematic review of the literature revealed six papers including 200 patients with a mean age of 32 years, a mean defect size of 3 cm. 2. and a follow up period from 2 to 5 years. Four of the studies compared microfracture to autologous chondrocyte implantation and two of them to osteochondral autologous transplantation. All patients were treated by the microfracture technique as described by Steadman and by a similar rehabilitation protocol which only allowed crutch-assisted touchdown weight bearing initially. Referring to the individual studies, a comparison of the pooled estimates of Hedges' g revealed that the two papers which evaluated the youngest patients provided the highest treatment effect. On the contrary, those two papers which focussed on the largest lesions, reported the worst improvement. Finally, the remaining two papers whose patients were characterized by similar age and defect size presented comparable results. The individual standardized effect sizes were combined into an overall best estimate. Its value was 1.678, measured in units of standard deviation, with the 95% confidence interval of [1.016; 2.340] resulting in different values of the average, to be expected treatment effect when it is measured in Lysholm Score (22.1), IKDC Score (26.5) and KOOS (15.2) points. Conclusions. Our results offer a clinically intuitive estimation of the average treatment effects on common clinical scales. Compared to the preoperative situation, a significant clinical improvement can be expected for each patient. Nevertheless, the magnitudes of these treatment effects are an approximation and must be interpreted cautiously. Furthermore, we did not succeed to confirm that young age and small lesion size have a beneficial effect on the clinical outcome

INTRODUCTION. The purpose of this study is to report results from a prospective multicenter study of a bioresorbable type I collagen scaffold used to replace tissue loss following irreparable lateral meniscus injuries. METHODS. 49 non-consecutive patients (33M/16F; mean age 30.5 yrs, range 14.7–54.7 yrs) with irreparable lateral meniscus tears or loss requiring surgical treatment were prospectively enrolled at one of 7 EU centers. 11 patients (22%) had acute injuries of the lateral meniscus, while 38 (78%) had prior surgeries to the involved meniscus. Implantation of the LCMI (now Lateral Menaflex) was performed arthroscopically using an all-inside suturing technique (FASTFIX) combined with inside-out sutures in the more anterior meniscus aspect. Forty-three patients were evaluated with a 2 to 4-year follow-up (FU); mean FU duration was 45 months (range, 33–53 m). Patients were evaluated clinically and by self-assessment using Tegner activity and Lysholm function scores, as well as the Visual Analog Scales (VAS) for pain, and a satisfaction questionnaire. Evaluations were performed pre-operatively, 6 months, 1 year, 2 and 4 years after surgery. X-ray and/or MR-images were taken pre-operatively, and at 1 year and 2 years after surgery. RESULTS. At 3 months after surgery, all patients were able to return to activities of daily living without limitation. Post-op. mean values of all evaluated patients showed statistically significant improvement compared to the preoperative scores. Mean Tegner scores increased from 3.0 to 5.2 at 4 years (0.8 points less than the pre-injury “recall” value); mean Lysholm improved from 63 to 91; mean pain (VAS) decreased from 36 to 8. At the 4-year time point, 86% of the patients stated that they were satisfied with their results (compared to 78% at the one year FU time point). Function and pain scores improved continuously with the highest score at the latest FU evaluation. All data were statistically significant (p<0.001, except for Tegner with p=0.03). MRI examination revealed no changes to the articular cartilage and joint space; however, the newly formed tissue did not present a signal consistent with fully mature native meniscus tissue. Reoperations were necessary in 5 patients (10%) during the FU time period: 3 of the reoperations were for persistent swelling and pain, which were classified as related to the device (6%) and were treated by synovectomy and debridement. Patients recovered without sequelae. The re-op. rate in this series is comparable to re-op. rates reported after lateral meniscal repair. DISCUSSION. Based on available results with a minimum 2 year FU, 90% of the patients benefited from the Lateral Menaflex as evidenced by improved clinical outcomes associated with gains in activity and function. Longer-term FU continues to determine the extent and duration of the benefits observed

INTRODUCTION. Autologous bone grafts are considered gold standard in the repair of bone defects. However they are limited in supply and are associated with donor site morbidity. This has led to the development of synthetic bone graft substitute (BGS) materials, many of which have been reported as being osteoinductive. The structure of the BGS is important and bone formation has been observed in scaffolds with a macroporous morphology. Smaller pores termed ‘strut porosity’ may also be important for osteoinduction. The aim of this study was to compare the osteoinductive ability of one silicate-substituted calcium phosphate (SiCaP) with differing strut porosities in an ectopic ovine model. Our hypothesis was that SiCaP with greater strut porosity would be more osteoinductive. METHODS. The osteoinduction of SiCaP BGS with two different strut porosities (AF and AF++) was investigated. The materials had an identical chemical composition and morphological structure but differing strut porosity (AF=22.5%, AF++=47%). Implants were inserted into the paraspinal muscles in skeletally mature sheep. Procedures were carried out in compliance with UK Home Office regulations. There were 12 implants in each group. Implants remained in vivo for 8 and 12 weeks and on retrieval were prepared for undecalcified histology. Sections were stained and examined using light microscopy. A line intersection method was used to quantify bone, implant and implant surface/bone contact within seven random regions of interest along each implant. A Mann-Whitney U test was used for statistical analysis where p values < 0.05 were considered significant. RESULTS. Bone formation was observed to be greater in the AF++ group at 8 (AF=0.2%+/−0.15; AF++=0.44%+/−0.12) and significantly higher at 12 weeks (AF=1.33% +/−0.84; AF++=6.17%+/−1.51) (p=0.04). Significantly higher implant surface/bone contact was observed in the AF++ group at 8 (AF=0.67%+/−0.52; AF++=3.30%+/−1.17) (p=0.04) and 12 weeks (AF=3.06%+/−1.89; AF++=21.82%+/−5.59) (p=0.01). The % implant measured was less in the AF++ group at 8 (AF=39.06%+/−1.26; AF++=33.09%+/−2.14) and 12 weeks (AF=36.05% +/−3.55; AF++=30.60%+/−2.29) but this was not significant. Histology revealed bone formation within BGS strut pores measuring < 50um. Endochondral and intramembranous ossification were also observed in both groups. DISCUSSION. The results indicate that higher strut porosity promotes greater osteoinduction in SiCaP materials. This could be attributed to the micropores providing a greater surface area for the action of growth factors and osteoblasts leading to the formation of bone at an earlier time point. Endochondral ossification was an unusual finding as this is usually associated with bone formation secondary to Bone Morphogenetic proteins (BMPs). This suggests that the osteoinductive mechanisms by SiCaP may involve cytokines such as BMPs