Predictors of Mortality in Head-Preserving Treatment for Dislocated Proximal Humerus Fractures: A Retrospective Analysis of 522 Cases with a Minimum Follow-Up of 5 Years.

PURPOSE: Proximal humerus fractures (PHFs) are among the most common fractures in elderly patients, but there is still inadequate knowledge about mortality risk factors after such injuries. In order to provide the best possible therapy, individual risk factors have to be considered and evaluated thoroughly. There is still controversy regarding treatment decisions for proximal humerus fractures, particularly for the elderly. METHODS: In this study, patient data from 522 patients with proximal humerus fractures were obtained from 2004 to 2014 at a Level 1 trauma centre. After a minimum follow-up of 5 years, the mortality rate was assessed, and independent risk factors were evaluated. RESULTS: A total of 383 patients (out of 522) were included in this study. For our patient collective, the mean follow-up was at 10.5 ± 3.2 years. The overall mortality rate was 43.8% in our respondent group and was not significantly impacted by concomitant injuries. The binary logistic regression model showed an increased risk for mortality by 10% per life year, a 3.9 times higher mortality risk for men and a 3.4 times higher risk for conservative treatment. The most powerful predictor was a Charlson Comorbidity Index of more than 2, with a 20 times higher mortality risk. CONCLUSIONS: Outstanding independent predictors of death in our patient collective were serious comorbidities, male patients, and conservative treatment. This patient-related information should influence the process of decision making for the individual treatment of patients with PHFs.

[Humeral bone defects in revision shoulder arthroplasty]. / Humerale Knochendefekte in der Revisionsendoprothetik.

BACKGROUND: Revision shoulder arthroplasty is mainly performed with reverse TSA and should consider proper adjustment of the length and the amount of bone loss in humeral reconstruction. Whilst epi-/metaphyseal bone loss can mostly be compensated easily by stemmed standard implants, advanced bone loss exceeding 2° requires the support of longer revision stems. EXTENSIVE HUMERAL BONE LOSS: Cementless fixation in the intact diaphyseal humerus is recommended in bone loss exceeding 2°, preferably with modular revision systems, because cemented reverse revision stems have higher loosening rates in the mid to long-term follow-up. In cases of advanced bone loss 3°-4° (more than 6-7 cm), structural humeral allografts should be considered to prevent instability and early loosening. Unfortunately, the access to fresh frozen allografts is very limited due to regulation of the German government in contrast to the situation in the US or Switzerland. Reverse tumor arthroplasty is an option with a higher complication rate and inferior function even when polyester mesh is used for ingrowth of soft tissues. DISTINCT DIAPHYSEAL DEFECTS: In bone loss 4°-5° the minimal anchorage length is mostly critical due to the curvature of the medullary canal. The fixation of a revision stem is only possible when at least 2-3 widths of the diaphyseal diameter are available. Custom-made implants with flanges or distal locking screws, or bipolar tumor arthroplasty may be required. Additionally, strut allografts can be useful to achieve stable fixation. Two-stage biological reconstruction in impaction-bone-graft or the Masquelet technique are rarely used as a salvage procedure.

Scaffold-guided bone regeneration in large volume tibial segmental defects.

Large volume losses in weight bearing long bones are a major challenge in clinical practice. Despite multiple innovations over the last decades, significant limitations subsist in current clinical treatment options which is driving a strong clinical demand for clinically translatable treatment alternatives, including bone tissue engineering applications. Despite these shortcomings, preclinical large animal models of large volume segmental bone defects to investigate the regenerative capacity of bone tissue engineering strategies under clinically relevant conditions are rarely described in literature. We herein present a newly established preclinical ovine animal model for the treatment of XL volume (19 cm3) segmental tibial defects. In eight aged male Merino sheep (age > 6 years) a mid-diaphyseal tibial segmental defect was created and stabilized with a 5.6 mm Dynamic Compression Plate (DCP). We present short-term (3 months) and long-term (12-15 months) results of a pilot study using medical grade Polycaprolactone-Tricalciumphosphate (mPCL-TCP) scaffolds combined with a dose of 2 mg rhBMP-7 delivered in Platelet-Rich- Plasma (PRP). Furthermore, detailed analyses of the mechanical properties of the scaffolds as well as interfragmentary movement (IFM) and DCP-surface strain in vitro and a comprehensive description of the surgical and post-surgery protocol and post-mortem analysis is given.

A preclinical large-animal model for the assessment of critical-size load-bearing bone defect reconstruction.

Critical-size bone defects, which require large-volume tissue reconstruction, remain a clinical challenge. Bone engineering has the potential to provide new treatment concepts, yet clinical translation requires anatomically and physiologically relevant preclinical models. The ovine critical-size long-bone defect model has been validated in numerous studies as a preclinical tool for evaluating both conventional and novel bone-engineering concepts. With sufficient training and experience in large-animal studies, it is a technically feasible procedure with a high level of reproducibility when appropriate preoperative and postoperative management protocols are followed. The model can be established by following a procedure that includes the following stages: (i) preoperative planning and preparation, (ii) the surgical approach, (iii) postoperative management, and (iv) postmortem analysis. Using this model, full results for peer-reviewed publication can be attained within 2 years. In this protocol, we comprehensively describe how to establish proficiency using the preclinical model for the evaluation of a range of bone defect reconstruction options.

TGF-ß Signalling is Suppressed under Pro-Hypertrophic Conditions in MSC Chondrogenesis Due to TGF-ß Receptor Downregulation.

BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) become hypertrophic in long term despite chondrogenic differentiation following the pathway of growth plate chondrocytes. This terminal differentiation leads to phenotypically unstable cartilage and was mirrored in vitro by addition of hypertrophy inducing medium. We investigated how intrinsic TGF-ß signaling is altered in pro-hypertrophic conditions. METHODS AND RESULTS: Human bone marrow derived MSC were chondrogenically differentiated in 3D culture. At day 14 medium conditions were changed to 1. pro-hypertrophic by addition of T3 and withdrawal of TGF-ß and dexamethasone 2. pro-hypertrophic by addition of BMP 4 and withdrawal of TGF-ß and dexamethasone and 3. kept in prochondrogenic medium conditions. All groups were treated with and without TGFß-type-1-receptor inhibitor SB431542 from day 14 on. Aggregates were harvested for histo- and immunohistological analysis at d14 and d28, for gene expression analysis (rt-PCR) on d1, d3, d7, d14, d17, d21 and d28 and for Western blot analysis on d21 and d28. Induction of hypertrophy was achieved in the pro-hypertrophic groups while expression of TGFß-type-1- and 2-receptor and Sox 9 were significantly downregulated compared to pro-chondrogenic conditions. Western blotting showed reduced phosphorylation of Smad 2 and 3 in hypertrophic samples, reduced TGF-ß-1 receptor proteins and reduced SOX 9. Addition of SB431542 did not initiate hypertrophy under pro-chondrogenic conditions, but was capable of enhancing hypertrophy when applied simultaneously with BMP-4. CONCLUSIONS: Our results suggest that the enhancement of hypertrophy in this model is a result of both activation of pro-hypertrophic BMP signaling and reduction of anti-hypertrophic TGFß signaling.

Expression of BMP and Actin Membrane Bound Inhibitor Is Increased during Terminal Differentiation of MSCs.

Chondrogenic differentiating mesenchymal stem cells (MSCs) are mimicking embryonal endochondral ossification and become hypertrophic. BMP (bone morphogenetic protein) and Activin Membrane Bound Inhibitor (BAMBI) is a pseudoreceptor that regulates the activity of transforming growth factor-ß (TGF-ß) and BMP signalling during chondrogenesis. Both TGF-ß and BMP signalling are regulators of chondrogenic cell differentiation. Human bone marrow derived MSCs were chondrogenically predifferentiated in aggregate culture for 14 days. Thereafter, one group was subjected to hypertrophy enhancing media conditions while controls were kept in chondrogenic medium until day 28. Histological evaluation, gene expression by PCR, and Western blot analysis were carried out at days 1, 3, 7, 14, 17, 21, and 28. A subset of cultures was treated with the BMP inhibitor Noggin to test for BMP dependent expression of BAMBI. Hypertrophic differentiated pellets showed larger cells with increased collagen 10 and alkaline phosphatase staining. There was significantly increased expression of BAMBI on gene expression and protein level in hypertrophic cultures compared to the chondrogenic control and increased BMP4 gene expression. Immunohistochemistry showed intense staining of BAMBI in hypertrophic cells. BAMBI expression was dose-dependently downregulated by Noggin. The pseudoreceptor BAMBI is upregulated upon enhancement of hypertrophy in MSC chondrogenic differentiation by a BMP dependent mechanism.

Poly(ε-caprolactone) Scaffolds Fabricated by Melt Electrospinning for Bone Tissue Engineering.

Melt electrospinning is a promising approach to manufacture biocompatible scaffolds for tissue engineering. In this study, melt electrospinning of poly(ε-caprolactone) onto structured, metallic collectors resulted in scaffolds with an average pore size of 250-300 µm and an average fibre diameter of 15 µm. Scaffolds were seeded with ovine osteoblasts in vitro. Cell proliferation and deposition of mineralised extracellular matrix was assessed using PicoGreen® (Thermo Fisher Scientific, Scoresby, Australia) and WAKO® HR II (WAKO, Osaka, Japan) calcium assays. Biocompatibility, cell infiltration and the growth pattern of osteoblasts on scaffolds was investigated using confocal microscopy and scanning electron microscopy. Osteoblasts proliferated on the scaffolds over an entire 40-day culture period, with excellent survival rates and deposited mineralized extracellular matrix. In general, the 3D environment of the structured melt electrospun scaffold was favourable for osteoblast cultures.

Microparticles for Sustained Growth Factor Delivery in the Regeneration of Critically-Sized Segmental Tibial Bone Defects.

This study trialled the controlled delivery of growth factors within a biodegradable scaffold in a large segmental bone defect model. We hypothesised that co-delivery of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) followed by bone morphogenetic protein-2 (BMP-2) could be more effective in stimulating bone repair than the delivery of BMP-2 alone. Poly(lactic-co-glycolic acid) (PLGA ) based microparticles were used as a delivery system to achieve a controlled release of growth factors within a medical-grade Polycaprolactone (PCL) scaffold. The scaffolds were assessed in a well-established preclinical ovine tibial segmental defect measuring 3 cm. After six months, mechanical properties and bone tissue regeneration were assessed. Mineralised bone bridging of the defect was enhanced in growth factor treated groups. The inclusion of VEGF and PDGF (with BMP-2) had no significant effect on the amount of bone regeneration at the six-month time point in comparison to BMP-2 alone. However, regions treated with VEGF and PDGF showed increased vascularity. This study demonstrates an effective method for the controlled delivery of therapeutic growth factors in vivo, using microparticles.

Higher Ratios of Hyaluronic Acid Enhance Chondrogenic Differentiation of Human MSCs in a Hyaluronic Acid-Gelatin Composite Scaffold.

Mesenchymal stem cells (MSCs) seeded on specific carrier materials are a promising source for the repair of traumatic cartilage injuries. The best supportive carrier material has not yet been determined. As natural components of cartilage's extracellular matrix, hyaluronic acid and collagen are the focus of biomaterial research. In order to optimize chondrogenic support, we investigated three different scaffold compositions of a hyaluronic acid (HA)-gelatin based biomaterial. METHODS: Human MSCs (hMSCs) were seeded under vacuum on composite scaffolds of three different HA-gelatin ratios and cultured in chondrogenic medium for 21 days. Cell-scaffold constructs were assessed at different time points for cell viability, gene expression patterns, production of cartilage-specific extracellular matrix (ECM) and for (immuno-)histological appearance. The intrinsic transforming growth factor beta (TGF-beta) uptake of empty scaffolds was evaluated by determination of the TGF-beta concentrations in the medium over time. RESULTS: No significant differences were found for cell seeding densities and cell viability. hMSCs seeded on scaffolds with higher ratios of HA showed better cartilage-like differentiation in all evaluated parameters. TGF-beta uptake did not differ between empty scaffolds. CONCLUSION: Higher ratios of HA support the chondrogenic differentiation of hMSCs seeded on a HA-gelatin composite scaffold.

Influence of preparation and football skill level on injury incidence during an amateur football tournament.

INTRODUCTION: Scientific studies on injury characteristics are rather common in professional football but not in amateur football despite the thousands of amateur football tournaments taking place worldwide each year. The purpose of this study was to evaluate the preparation and injury patterns of players of two different football skill levels who participated in an international amateur football tournament. METHODS: In a prospective cohort study, an international amateur football tournament of medical doctors in 2011 was analysed with regard to training and warm-up preparation, the level of football played before the tournament and injury data during the tournament by means of standardised injury definitions and data samples for football. RESULTS: Amateur players of registered football clubs had higher training exposure before the tournament (p < 0.001) than recreational players and had more frequently performed warm-up programmes (p < 0.001). Recreational football players showed a significantly higher overall injury incidence (p < 0.002), particularly of overuse injuries (p < 0.001), during the tournament than amateur players. In almost 75% of players in both groups, the body region most affected by injuries and complaints was the lower extremities. Orthopaedic and trauma surgeons had the lowest overall injury incidence and anaesthetists the highest (p = 0.049) during the tournament. CONCLUSION: For the first time, this study presents detailed information on the injury incidence and injury patterns of an amateur football tournament. Less-trained recreational players sustained significantly more injuries than better-trained amateur players, probably due to the lack of sufficient preparation before the tournament. Preventive strategies against overuse and traumatic injuries of recreational football players should start with regular training and warm-up programmes in preparation for a tournament.

PMMA-augmented SI screw: a biomechanical analysis of stiffness and pull-out force in a matched paired human cadaveric model.

INTRODUCTION: Current literature data and clinical experience show that the number of pelvic fractures continuously rises due to the increasing elderly population. In the elderly with suspected osteoporosis additional implant augmentation with bone cement seems to be an option to avoid secondary displacement. There are no reported biomechanical data in the literature comparing the fixation strength (and anchorage) of standard and augmented SI screws so far. The purpose of this study was to assess the biomechanical performance of cement-augmented versus non-augmented SI screws in a human cadaveric pelvis model. MATERIAL AND METHODS: Six human cadaveric pelvises preserved with the method of Thiel were used in this study. Each pelvis was split to a pair of 2 hemi-pelvises, assigned to 2 different groups for instrumentation with one non-augmented or one contralateral cement-augmented SI screw, placed in the body of S1 in a randomized fashion. The osteosynthesis followed a standard procedure with 3D controlled percutaneous iliosacral screw positioning. A biomechanical setup for a quasistatic pullout test of each SI screw was used. Construct stiffness and maximum pullout force were calculated from the load-displacement curve of the machine data. Statistical evaluation was performed at a level of significance p = .05 for all statistical tests. RESULTS: Stiffness and pullout force in the augmented group (501.6 N/mm ± 123.7, 1336.8 N ± 221.1) were significantly higher than in the non-augmented one (289.7 N/mm ± 97.1, 597.7 N ± 115.5), p = .04 and p = .014, respectively. BMD influenced significantly the pullout force in all study groups. CONCLUSION: Cement augmentation significantly increased the fixation strength in iliosacral screw osteosynthesis of the sacrum in a biomechanical human cadaveric model.

A novel locking screw hip stem to achieve immediate stability in total hip arthroplasty: A biomechanical study.

INTRODUCTION: As total hip arthroplasty is now applicable for younger, healthier, and more active patients, bone preservation becomes even more essential, and proximal fixation, resulting in less stress shielding, draws special attention with focus on new strategies and implant designs. Recently, a new type of non-cemented fixation of the femoral component, featured with the locking screw hip (LSH) stem, was developed by Scyon Orthopaedics AG (Au-Waedenswil, Switzerland). The idea to rigidly fix the femoral component of a prosthesis for total hip replacement in this fashion evolved from the very good results achieved with the internal point-contact fixator PC-Fix. The purpose of this study was to investigate the unique characteristics of the LSH-stem and to assess its biomechanical performance in comparison to a conventional cemented prosthesis (Mueller straight stem). MATERIAL AND METHODS: Six paired human cadaveric femora were preserved with the method of Thiel, split in two study groups, implanted with either cemented Mueller straight stem or LSH-stem prostheses and biomechanically tested under progressively increasing axial loading until catastrophic failure. Bone mineral density (BMD) of all femora was evaluated in the femoral head prior to implantation. Axial construct stiffness, failure load and cycles to failure were calculated from the machine data and statistically evaluated at a level of significance p = 0.05. RESULTS: No statistically significant difference between the LSH-stem and the Mueller straight stem was found in terms of axial construct stiffness (2031.5 N/mm ± 483.1 N/mm and 2403.6 N/mm ± 705.2 N/mm, p = 0.115), failure load (4958.8 N ± 1094.1 N and 5907.2 N ± 1562.8 N, p = 0.138) and cycles to failure (7917.7 ± 2188.1 and 9814.3 ± 3125.6, p = 0.138). BMD showed no significant difference between the two study groups, p = 0.616. CONCLUSION: The LSH-stem seems to be stable enough to carry loads experienced during the rehabilitation period of a patient after THR. Its stability, which is similar to that of the Mueller straight stem, may justify the clinical application of the LSH-stem under thorough investigation.

Delayed minimally invasive injection of allogenic bone marrow stromal cell sheets regenerates large bone defects in an ovine preclinical animal model.

Cell-based tissue engineering approaches are promising strategies in the field of regenerative medicine. However, the mode of cell delivery is still a concern and needs to be significantly improved. Scaffolds and/or matrices loaded with cells are often transplanted into a bone defect immediately after the defect has been created. At this point, the nutrient and oxygen supply is low and the inflammatory cascade is incited, thus creating a highly unfavorable microenvironment for transplanted cells to survive and participate in the regeneration process. We therefore developed a unique treatment concept using the delayed injection of allogenic bone marrow stromal cell (BMSC) sheets to regenerate a critical-sized tibial defect in sheep to study the effect of the cells' regeneration potential when introduced at a postinflammatory stage. Minimally invasive percutaneous injection of allogenic BMSCs into biodegradable composite scaffolds 4 weeks after the defect surgery led to significantly improved bone regeneration compared with preseeded scaffold/cell constructs and scaffold-only groups. Biomechanical testing and microcomputed tomography showed comparable results to the clinical reference standard (i.e., an autologous bone graft). To our knowledge, we are the first to show in a validated preclinical large animal model that delayed allogenic cell transplantation can provide applicable clinical treatment alternatives for challenging bone defects in the future.

RFE based chondroplasty in wrist arthroscopy indicates high risk for chrondocytes especially for the bipolar application.

BACKGROUND: The application of radiofrequency energy (RFE) has become widespread for surgical performed chondroplasty especially due to the anticipated sealing effect, however the safety of this procedure in the wrist remains unclear. The purpose of this study was to investigate the subchondral temperature during radiofrequency energy (RFE) application simulating chondroplasty in an arthroscopic setting of the wrist. METHODS: A chondroplasty of the lunate fossa was performed during an arthroscopy setting on 14 cadaver arms using monopolar or bipolar RFE. The temperature was recorded simultaneously from 7 predefined anatomical landmarks. RESULTS: The mean temperature for both application modes did not exceed more than 30°C at all measured points, except for the lunate fossa. The highest subchondral measured peak temperature was 49.35°C (monopolar) and 69.21°C (bipolar) in the lunate fossa. In addition, the temperature decreased for both radiofrequency (RF) devices depending on the distance of the sensors to the RF-probe. CONCLUSION: It remains to be questionable how safe RFE can be used for chondroplasty in wrist arthroscopy under continuous irrigation and constant movement to obtain the desired sealing effect. However, the bipolar device should be applied with more caution since peak temperature in the lunate fossa almost reached 70°C even under continuous irrigation.

Are applied growth factors able to mimic the positive effects of mesenchymal stem cells on the regeneration of meniscus in the avascular zone?

Meniscal lesions in the avascular zone are still a problem in traumatology. Tissue Engineering approaches with mesenchymal stem cells (MSCs) showed successful regeneration of meniscal defects in the avascular zone. However, in daily clinical practice, a single stage regenerative treatment would be preferable for meniscus injuries. In particular, clinically applicable bioactive substances or isolated growth factors like platelet-rich plasma (PRP) or bone morphogenic protein 7 (BMP7) are in the focus of interest. In this study, the effects of PRP and BMP7 on the regeneration of avascular meniscal defects were evaluated. In vitro analysis showed that PRP secretes multiple growth factors over a period of 8 days. BMP7 enhances the collagen II deposition in an aggregate culture model of MSCs. However applied to meniscal defects PRP or BMP7 in combination with a hyaluronan collagen composite matrix failed to significantly improve meniscus healing in the avascular zone in a rabbit model after 3 months. Further information of the repair mechanism at the defect site is needed to develop special release systems or carriers for the appropriate application of growth factors to support biological augmentation of meniscus regeneration.

Percutaneous screw placement in acetabular posterior column surgery: gender differences in implant positioning.

Percutaneous reduction and periarticular screw implantation techniques have been successfully introduced in acetabular surgery. Image guided navigation techniques might be beneficial in increasing accuracy. However, a thorough understanding of standard values is needed to oversee pitfalls. This cadaver study was designed to identify reliable angulation values for screw implantation in the posterior acetabular column and to provide knowledge of the bony thickness for the periarticular corridor. Gender differences were specifically addressed. 27 embalmed cadaveric hemipelvic specimens (13 male, 14 female) were used. After soft-tissue removal posterior column acetabular screw placement was conducted by one experienced orthopaedic trauma surgeon under visibility. Radiographic verification of ideal screw placement was followed by radiographic assessment in three standard views and angulation values were assessed. Through bony dissection the maximal periarticular canal width was assessed. Various angulation values with regard to anatomical landmarks could be determined in the anteroposterior radiograph, as well as in the iliac oblique and the obturator oblique view. Gender differences were significant for all reference points with the pubic rami involved. The minimal canal width was 1.1cm in female and 1.6 cm in male specimen. The findings provide standard values for safe passages in percutaneous posterior column acetabular surgery. Gender differences have to be taken in consideration when planning the drill corridor. By adherence to standard values, screw placement can be performed safely.

Thyroid hormone-induced hypertrophy in mesenchymal stem cell chondrogenesis is mediated by bone morphogenetic protein-4.

Chondrogenic differentiating mesenchymal stem cells (MSCs) express markers of hypertrophic growth plate chondrocytes. As hypertrophic cartilage undergoes ossification, this is a concern for the application of MSCs in articular cartilage tissue engineering. To identify mechanisms that elicit this phenomenon, we used an in vitro hypertrophy model of chondrifying MSCs for differential gene expression analysis and functional experiments with the focus on bone morphogenetic protein (BMP) signaling. Hypertrophy was induced in chondrogenic MSC pellet cultures by transforming growth factor ß (TGFß) and dexamethasone withdrawal and addition of triiodothyronine. Differential gene expression analysis of BMPs and their receptors was performed. Based on these results, the in vitro hypertrophy model was used to investigate the effect of recombinant BMP4 and the BMP inhibitor Noggin. The enhancement of hypertrophy could be shown clearly by an increased cell size, alkaline phosphatase activity, and collagen type X deposition. Upon induction of hypertrophy, BMP4 and the BMP receptor 1B were upregulated. Addition of BMP4 further enhanced hypertrophy in the absence, but not in the presence of TGFß and dexamethasone. Thyroid hormone induced hypertrophy by upregulation of BMP4 and this induced enhancement of hypertrophy could be blocked by the BMP antagonist Noggin. BMP signaling is an important modulator of the late differentiation stages in MSC chondrogenesis and the thyroid hormone induces this pathway. As cartilage tissue engineering constructs will be exposed to this factor in vivo, this study provides important insight into the biology of MSC-based cartilage. Furthermore, the possibility to engineer hypertrophic cartilage may be helpful for critical bone defect repair.

Polycaprolactone scaffold and reduced rhBMP-7 dose for the regeneration of critical-sized defects in sheep tibiae.

The transplantation of autologous bone graft as a treatment for large bone defects has the limitation of harvesting co-morbidity and limited availability. This drives the orthopaedic research community to develop bone graft substitutes. Routinely, supra-physiological doses of bone morphogenetic proteins (BMPs) are applied perpetuating concerns over undesired side effects and cost of BMPs. We therefore aimed to design a composite scaffold that allows maintenance of protein bioactivity and enhances growth factor retention at the implantation site. Critical-sized defects in sheep tibiae were treated with the autograft and with two dosages of rhBMP-7, 3.5 mg and 1.75 mg, embedded in a slowly degradable medical grade poly(ε-caprolactone) (PCL) scaffold with ß-tricalcium phosphate microparticles (mPCL-TCP). Specimens were characterised by biomechanical testing, microcomputed tomography and histology. Bridging was observed within 3 months for the autograft and both rhBMP-7 treatments. No significant difference was observed between the low and high rhBMP-7 dosages or between any of the rhBMP-7 groups and autograft implantation. Scaffolds alone did not induce comparable levels of bone formation compared to the autograft and rhBMP-7 groups. In summary, the mPCL-TCP scaffold with the lower rhBMP-7 dose led to equivalent results to autograft transplantation or the high BMP dosage. Our data suggest a promising clinical future for BMP application in scaffold-based bone tissue engineering, lowering and optimising the amount of required BMP.

Stem cell-based tissue-engineering for treatment of meniscal tears in the avascular zone.

Meniscal tears in the avascular zone have a poor self-healing potential, however partial meniscectomy predisposes the knee for early osteoarthritis. Tissue engineering with mesenchymal stem cells and a hyaluronan collagen based scaffold is a promising approach to repair meniscal tears in the avascular zone. 4 mm longitudinal meniscal tears in the avascular zone of lateral menisci of New Zealand White Rabbits were performed. The defect was left empty, sutured with a 5-0 suture or filled with a hyaluronan/collagen composite matrix without cells, with platelet rich plasma or with autologous mesenchymal stem cells. Matrices with stem cells were in part precultured in chondrogenic medium for 14 days prior to the implantation. Menisci were harvested at 6 and 12 weeks. The developed repair tissue was analyzed macroscopically, histologically and biomechanically. Untreated defects, defects treated with suture alone, with cell-free or with platelet rich plasma seeded implants showed a muted fibrous healing response. The implantation of stem cell-matrix constructs initiated fibrocartilage-like repair tissue, with better integration and biomechanical properties in the precultured stem cell-matrix group. A hyaluronan-collagen based composite scaffold seeded with mesenchymal stem cells is more effective in the repair avascular meniscal tear with stable meniscus-like tissue and to restore the native meniscus.