Werner Krutsch

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.

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.

Adipose Tissue-Derived Stem Cell Secreted IGF-1 Protects Myoblasts from the Negative Effect of Myostatin

Myostatin, a TGF-β family member, is associated with inhibition of muscle growth and differentiation and might interact with the IGF-1 signaling pathway. Since IGF-1 is secreted at a bioactive level by adipose tissue-derived mesenchymal stem cells (ASCs), these cells (ASCs) provide a therapeutic option for Duchenne Muscular Dystrophy (DMD). But the protective effect of stem cell secreted IGF-1 on myoblast under high level of myostatin remains unclear. In the present study murine myoblasts were exposed to myostatin under presence of ASCs conditioned medium and investigated for proliferation and apoptosis. The protective effect of IGF-1 was further examined by using IGF-1 neutralizing and receptor antibodies as well as gene silencing RNAi technology. MyoD expression was detected to identify impact of IGF-1 on myoblasts differentiation when exposed to myostatin. IGF-1 was accountable for 43.6% of the antiapoptotic impact and 48.8% for the proliferative effect of ASCs conditioned medium. Furthermore, IGF-1 restored mRNA and protein MyoD expression of myoblasts under risk. Beside fusion and transdifferentiation the beneficial effect of ASCs is mediated by paracrine secreted cytokines, particularly IGF-1. The present study underlines the potential of ASCs as a therapeutic option for Duchenne muscular dystrophy and other dystrophic muscle diseases.

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.

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.

Clinical and Radiological Regeneration of Large and Deep Osteochondral Defects of the Knee by Bone Augmentation Combined With Matrix-Guided Autologous Chondrocyte Transplantation

Background: Large osteochondral defects of the knee are a challenge for regenerative treatment. While matrix-guided autologous chondrocyte transplantation (MACT) represents a successful treatment for chondral defects, the treatment potential in combination with bone grafting by cancellous bone or bone block augmentation for large and deep osteochondral defects has not been evaluated. Purpose: To evaluate 1- to 3-year clinical outcomes and radiological results on magnetic resonance imaging (MRI) after the treatment of large osteochondral defects of the knee with bone augmentation and MACT. Special emphasis is placed on different methods of bone grafting (cancellous bone grafting or bone block augmentation). Study Design: Case series; Level of evidence, 4. Methods: Fifty-one patients were included. Five patients were lost to follow-up. This left 46 patients (mean age, 28.2 years) with a median follow-up time of 2 years. The 46 patients had 47 deep, large osteochondral defects of the knee joint (1 patient with bilateral defects; mean defect size, 6.7 cm2). The origin of the osteochondral defects was osteochondritis dissecans (n = 34), osteonecrosis (n = 8), or subchondral cysts (n = 5). Depending on the depth, all defects were treated by cancellous bone grafting (defect depth ≤10 mm; n = 16) or bone block augmentation (defect depth >10 mm; n = 31) combined with MACT. Clinical outcomes were followed at 3 months, 6 months, 1 year, 2 years, and 3 years and evaluated using the International Knee Documentation Committee (IKDC) score and Cincinnati score. A magnetic resonance imaging (MRI) evaluation was performed at 1 and 2 years, and the magnetic resonance observation of cartilage repair tissue (MOCART) score with additional specific subchondral bone parameters (bone regeneration, bone signal quality, osteophytes, sclerotic areas, and edema) was analyzed. Results: The clinical outcome scores revealed a significant increase at follow-up (6 months to 3 years) compared with the preclinical results. The median IKDC score increased from 42.6 preoperatively to 75.3 at 1 year, 79.7 at 2 years, and 84.3 at 3 years. The median Cincinnati score significantly increased from 39.8 preoperatively to 72.0 at 1 year, 78.0 at 2 years, and 80.3 at 3 years. The MRI evaluation revealed a MOCART score of 82.6 at 1 year without a deterioration at the later follow-up time point. Especially, the subchondral bone analysis showed successful regeneration. All bone blocks and cancellous bone grafts were integrated in the bony defects, and no chondrocyte transplant failure could be detected throughout the follow-up. Conclusion: Large and deep osteochondral defects of the knee joint can be treated successfully with bone augmentation and MACT. The treatment of shallow bony defects with cancellous bone grafting and deep bony defects with bone block augmentation shows promising results.

Analysis of 213 currently used rehabilitation protocols in foot and ankle fractures.

INTRODUCTION Fractures of the ankle, hind- and midfoot are amongst the five most common fractures. Besides initial operative or non-operative treatment, rehabilitation of the patients plays a crucial role for fracture union and long term functional outcome. Limited evidence is available with regard to what a rehabilitation regimen should include and what guidelines should be in place for the initial clinical course of these patients. This study therefore investigated the current rehabilitation concepts after fractures of the ankle, hind- and midfoot. METHODS Written rehabilitation protocols provided by orthopedic and trauma surgery institutions in terms of recommendations for weight bearing, range of motion (ROM), physiotherapy and choice of orthosis were screened and analysed. All protocols for lateral ankle fractures type AO 44A1, AO 44B1 and AO 44C1, for calcaneal fractures and fractures of the metatarsal as well as other not specific were included. Descriptive analysis was carried out and statistical analysis applied where appropriate. RESULTS 209 rehabilitation protocols for ankle fractures type AO 44B1 and AO 44C1, 98 for AO 44A1, 193 for metatarsal fractures, 142 for calcaneal fractures, 107 for 5(th) metatarsal base fractures and 70 for 5(th) metatarsal Jones fractures were evaluated. The mean time recommended for orthosis treatment was 6.04 (SD 0.04) weeks. While the majority of protocols showed a trend towards increased weight bearing and increased ROM over time, the best consensus was noted for weight bearing recommendations. CONCLUSION Our study shows that there exists a huge variability in rehabilitation of fractures of the ankle-, hind- and midfoot. This may be contributed to a lack of consensus (e.g. missing publication of guidelines), individualized patient care (e.g. in fragility fractures) or lack of specialization. This study might serve as basis for prospective randomized controlled trials in order to optimize rehabilitation for these common fractures.

Autologous chondrocyte implantation for cartilage repair: current perspectives

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Orthopedic Research and Reviews 2015:7 149–158 Orthopedic Research and Reviews Dovepress

Arthroscopic three dimensional autologous chondrocyte transplantation with navigation-guided cartilage defect size assessment

IntroductionThe treatment of large full thickness cartilage defects with matrix guided autologous chondrocyte transplantation shows promising results. However, in many cases an arthrotomy is needed to implant the cell seeded scaffolds. Recently techniques have been developed for arthroscopically guided ACT implantation. Correct defect mapping, to assess size and depth of the chondral lesions, and precise scaffold preparation and fixation are crucial for successful chondrocyte transplantation and remain to be not sufficiently optimized.MethodIn the present study, the geometries of two cartilage defects in cadaver knees were three times assessed, measured and transferred to biodegradable scaffolds with a navigation system by three different executors. The scaffolds were arthroscopically implanted into the cartilage defects.ResultsThe cartilage defect assessment was reproducible between all executors for all defect geometries. The implanted scaffolds showed a correct defect filling.ConclusionThe study showed the feasibility of an arthroscopic implantation of scaffolds for autologous chondrocytes transplantation. Navigation was a useful tool to exactly assess the cartilage defect geometry and allowed a precise transfer of navigated cartilage defect geometries for individualized scaffold preparation. Navigation can help to accomplish and optimize arthroscopically guided chondrocyte transplantations.

Injury prevention and return to play strategies in elite football: no consent between players and team coaches

IntroductionInjuries are a common problem in football. To improve prevention strategies, the players’ (p) and coaches’ (c) views need to be disclosed as they have a strong impact on return to play decisions. The aim of this study is to reveal current opinions with regard to injury prevention and return to play strategies to introduce new strategies in elite football.Materials and methodsIn a retrospective data analysis of elite salaried football players (n = 486) and team coaches (n = 88), a detailed investigation by means of a standardized questionnaire was carried out. In a preseason period of the 2015/16 season and as part of a large interventional research project in elite salaried German football, a request about players’ and team coaches’ knowledge and opinions was performed. Topics such as injury prevention, return to play after injuries, the importance of screening tests, general problems of injuries in football, or the decision-making in terms of prevention and return to play in elite football were investigated.ResultsThe study revealed a high interest in injury prevention and screening tests among players and coaches (p 82.5%; c 99.1%). The participants of the study reported warm-up exercises (p 76.4%; c 74.7%), regeneration training (p 54.1%; c 56.3%), and core stability (p 53.8; c 70.1%) as the most important prevention methods, but the additional investigation of the teams’ current daily training routine showed that the transfer is incomplete. Coaches are more familiar with scientific published warm-up programs like FIFA 11 + than players (42.5 vs. 12.6; p < 0.001). Knee injuries (p 90.7%; c 93.1%) and ACL injuries in particular were reported as the most severe and common problem in elite football. Players and coaches expressed different attitudes concerning return to play decisions. While players want to decide themselves (81.4%), team coaches consult medical advice ahead of the decision of return to play after injuries (83.5%; p < 0.001). Decisions against the doctor’s recommendation are often made by both groups (p 64.4% vs. c 87.1%; p < 0.001).ConclusionThe basic knowledge of prevention and injuries is sufficient in elite football, but the transfer from theoretical knowledge to practical routine is suboptimal. The study also shows possibilities to improve the prevention process and communication between players, coaches, doctors, and physiotherapists, while there is no consent between players and coaches regarding return to play decision.