Infraspinatus shift for massive, posterosuperior tears yields good clinical outcome.

AIM: To evaluate the functional outcome of partial reconstruction margin convergence in the treatment of massive, irreparable posterosuperior rotator cuff tear (RCT). METHODS: This retrospective, single-center study included all patients that were operated by means of a partial repair and infraspinatus shift for a massive, posterosuperior cuff tear between 2009 and 2016, either in arthroscopic or mini-open technique. Outcome measures included sex- and age-adapted Constant Score (saCS), Western Ontario Rotator Cuff (WORC) Index, Disabilities of Arm, Shoulder and Hand Scores (DASH), and relative effect per patient (REPP). RESULTS: Fifty-six shoulders in 54 patients (mean age: 66 ± 7 years) were evaluated at a mean follow-up of 40 ± 9 months. The mean tear size was Bateman 3.1 ± 0.7 and Patte 2.3 ± 0.4. All clinical scores showed improvement. The saCS improved from 64.1 ± 13.4 to 90.4 ± 13.7 (p < 0.0001), the DASH score from 51.8 ± 9.4 to 10.2 ± 13.4 (p < 0.0001) and the WORC index from 47.1% ± 8.6 to 87.9% ± 13.7 (p < 0.0001). The abduction strength of the affected side (1.7 ± 1.6 kg) was not restored to the same level as the contralateral side (5.4 ± 2.7 kg, p < 0.0001). CONCLUSION: Partial cuff repair for posterosuperior, massive cuff tears yields good clinical outcome with a low rate of complications and high proportion of good and excellent responders. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Practical Relevance of Institutional Guidelines in Translational Large Animal Studies of Cartilage Repair-A Multidisciplinary Survey.

Background and Objective: Translational large animal models are inevitable to transfer cartilage repair methods into clinical practice. Guidelines for these trials have been published by guiding agencies (FDA, ASTM, EMEA) including recommendations for study descriptors and study outcomes. However, practical adherence to these recommendations is not achieved in all aspects. This study includes an assessment of the recommended aspects regarding practical relevance in large animal models for cartilage repair by professionals in the field. Materials and Methods: In an online based survey, 11 aspects regarding study design and 13 aspects regarding study outcome from previously published guidelines were evaluated (0-10 points, with 10 being most important) by study participants. Additionally, the survey contained questions related to professional experience (years), professional focus (preclinical, clinical, veterinarian, industry) and the preferred translational large animal model for cartilage repair. Results: The total number of survey participants was 37. Rated as most important for study design parameters was lesion size (9.54 pts., SD 0.80) followed by study duration (9.43 pts., SD 1.21); and method of scaffold fixation (9.08 pts., SD 1.30) as well as depth of the lesion (9.03 pts., SD 1.77). The most important aspects of study outcome were considered histology (9.41 pts., SD 0.86) and defect filling (8.97 pts., SD 1.21), while gene expression was judged as the least important (6.11 pts., SD 2.46) outcome. A total of 62.2% of all participants were researchers, 18.9% clinicians, 13.5% veterinarians and 5.4% industry employees. Conclusions: In translational research, recommendations published by guiding agencies receive broad theoretical consensus within the community, including both clinically and preclinically orientated scientists. However, implementation into practical research lacks in major aspects. Ongoing re-evaluation of the guidelines under involvement of all stakeholders and approaches to overcome financial and infrastructural limitations could support the acceptance of the guidance documents and contribute to standardization in the field.

Tenomodulin knockout mice exhibit worse late healing outcomes with augmented trauma-induced heterotopic ossification of Achilles tendon.

Heterotopic ossification (HO) represents a common problem after tendon injury with no effective treatment yet being developed. Tenomodulin (Tnmd), the best-known mature marker for tendon lineage cells, has important effects in tendon tissue aging and function. We have reported that loss of Tnmd leads to inferior early tendon repair characterized by fibrovascular scaring and therefore hypothesized that its lack will persistently cause deficient repair during later stages. Tnmd knockout (Tnmd-/-) and wild-type (WT) animals were subjected to complete Achilles tendon surgical transection followed by end-to-end suture. Lineage tracing revealed a reduction in tendon-lineage cells marked by ScleraxisGFP, but an increase in alpha smooth muscle actin myofibroblasts in Tnmd-/- tendon scars. At the proliferative stage, more pro-inflammatory M1 macrophages and larger collagen II cartilaginous template were detected in this group. At the remodeling stage, histological scoring revealed lower repair quality in the injured Tnmd-/- tendons, which was coupled with higher HO quantified by micro-CT. Tendon biomechanical properties were compromised in both groups upon injury, however we identified an abnormal stiffening of non-injured Tnmd-/- tendons, which possessed higher static and dynamic E-moduli. Pathologically thicker and abnormally shaped collagen fibrils were observed by TEM in Tnmd-/- tendons and this, together with augmented HO, resulted in diminished running capacity of Tnmd-/- mice. These novel findings demonstrate that Tnmd plays a protecting role against trauma-induced endochondral HO and can inspire the generation of novel therapeutics to accelerate repair.

Post-operative septic arthritis after arthroscopy: modern diagnostic and therapeutic concepts.

PURPOSE: Septic arthritis is a significant complication following arthroscopic surgery, with an estimated overall incidence of less than 1%. Despite the low incidence, an appropriate diagnostic and therapeutic pathway is required to avoid serious long-term consequences, eradicate the infection, and ensure good treatment outcomes. The aim of this current review article is to summarize evidence-based literature regarding diagnostic and therapeutic options of post-operative septic arthritis after arthroscopy. METHODS: Through a literature review, up-to-date treatment algorithms and therapies have been identified. Additionally, a supportive new algorithm is proposed for diagnosis and treatment of suspected septic arthritis following arthroscopic intervention. RESULTS: A major challenge in diagnostics is the differentiation of the post-operative status between a non-infected hyperinflammatory joint versus septic arthritis, due to clinical symptoms, (e.g., rubor, calor, or tumor) can appear identical. Therefore, joint puncture for microbiological evaluation, especially for fast leukocyte cell-count diagnostics, is advocated. A cell count of more than 20.000 leukocyte/µl with more than 70% of polymorphonuclear cells is the generally accepted threshold for septic arthritis. CONCLUSION: The therapy is based on arthroscopic or open surgical debridement for synovectomy and irrigation of the joint, in combination with an adequate antibiotic therapy for 6-12 weeks. Removal of indwelling hardware, such as interference screws for ACL repair or anchors for rotator cuff repair, is recommended in chronic cases. LEVEL OF EVIDENCE: IV.

Reversed shoulder arthroplasty leads to significant histological changes of the deltoid muscle: a prospective intervention trial.

INTRODUCTION: Reverse shoulder arthroplasty (RSA) shows promising short- and mid-term results in cuff tear arthropathy. However, functional impairments are described in long-term findings. Micromorphological changes in the periarticular musculature could be in part responsible for this, but have not yet been analysed. Thus, histological changes of the deltoid muscle and their association to the functional outcome were evaluated in this study. MATERIAL AND METHODS: A total of 15 patients treated with RSA were included in this prospective study. Functional outcome was assessed using the Constant Score (CS) and the DASH (disabilities of the arm, shoulder and hand) Score before RSA and after a mean follow-up of 12 months. Deltoid muscle biopsies were harvested intraoperatively and 12 months postoperatively. Mean deltoid muscle fibre area (MMFA) was calculated histologically after haematoxylin-eosin staining. RESULTS: Postoperative shoulder function significantly improved within 12 months (CS: Δ 37.4 ± 22.6, p = 0.001; DASH: Δ 27.1 ± 29.1, p = 0.006). The MMFA significantly decreased (p = 0.02), comparing the results from the intraoperative biopsy (MMFA: 8435.8 µm2, SD ± 5995.9 µm2) to the 12 months biopsy (MMFA: 5792. µm2, SD ± 3223.6 µm2). No correlation could be found between the functional score results and MMFA. CONCLUSION: Signs of deltoid muscle changes in terms of a reduced MMFA can be detected 1 year after RSA and thus already a long time before long-term functional impairments become apparent. Further studies with larger patient series and longer follow-up periods as well as extended histological assessments and simultaneous radiological examinations are required.

Rebuilding Tendons: A Concise Review on the Potential of Dermal Fibroblasts.

Tendons are vital to joint movement by connecting muscles to bones. Along with an increasing incidence of tendon injuries, tendon disorders can burden the quality of life of patients or the career of athletes. Current treatments involve surgical reconstruction and conservative therapy. Especially in the elderly population, tendon recovery requires lengthy periods and it may result in unsatisfactory outcome. Cell-mediated tendon engineering is a rapidly progressing experimental and pre-clinical field, which holds great potential for an alternative approach to established medical treatments. The selection of an appropriate cell source is critical and remains under investigation. Dermal fibroblasts exhibit multiple similarities to tendon cells, suggesting they may be a promising cell source for tendon engineering. Hence, the purpose of this review article was in brief, to compare tendon to dermis tissues, and summarize in vitro studies on tenogenic differentiation of dermal fibroblasts. Furthermore, analysis of an open source Gene Expression Omnibus (GEO) data repository was carried out, revealing great overlap in the molecular profiles of both cell types. Lastly, a summary of in vivo studies employing dermal fibroblasts in tendon repair as well as pilot clinical studies in this area is included. Altogether, dermal fibroblasts hold therapeutic potential and are attractive cells for rebuilding injured tendons.

Physioxia Expanded Bone Marrow Derived Mesenchymal Stem Cells Have Improved Cartilage Repair in an Early Osteoarthritic Focal Defect Model.

Focal early osteoarthritis (OA) or degenerative lesions account for 60% of treated cartilage defects each year. The current cell-based regenerative treatments have an increased failure rate for treating degenerative lesions compared to traumatic defects. Mesenchymal stem cells (MSCs) are an alternative cell source for treating early OA defects, due to their greater chondrogenic potential, compared to early OA chondrocytes. Low oxygen tension or physioxia has been shown to enhance MSC chondrogenic matrix content and could improve functional outcomes of regenerative therapies. The present investigation sought to develop a focal early OA animal model to evaluate cartilage regeneration and hypothesized that physioxic MSCs improve in vivo cartilage repair in both, post-trauma and focal early OA defects. Using a rabbit model, a focal defect was created, that developed signs of focal early OA after six weeks. MSCs cultured under physioxia had significantly enhanced in vitro MSC chondrogenic GAG content under hyperoxia with or without the presence of interleukin-1ß (IL-1ß). In both post-traumatic and focal early OA defect models, physioxic MSC treatment demonstrated a significant improvement in cartilage repair score, compared to hyperoxic MSCs and respective control defects. Future investigations will seek to understand whether these results are replicated in large animal models and the underlying mechanisms involved in in vivo cartilage regeneration.

Aged Tendon Stem/Progenitor Cells Are Less Competent to Form 3D Tendon Organoids Due to Cell Autonomous and Matrix Production Deficits.

Tendons are dense connective tissues, which are critical for the integrity and function of our musculoskeletal system. During tendon aging and degeneration, tendon stem/progenitor cells (TSPCs) experience profound phenotypic changes with declined cellular functions that can be linked to the known increase in complications during tendon healing process in elderly patients. Tissue engineering is a promising approach for achieving a complete recovery of injured tendons. However, use of autologous cells from aged individuals would require restoring the cellular fitness prior to implantation. In this study, we applied an established cell sheet model for in vitro tenogenesis and compared the sheet formation of TSPC derived from young/healthy (Y-TSPCs) versus aged/degenerative (A-TSPCs) human Achilles tendon biopsies with the purpose to unravel differences in their potential to form self-assembled three-dimensional (3D) tendon organoids. Using our three-step protocol, 4 donors of Y-TSPCs and 9 donors of A-TSPCs were subjected to cell sheet formation and maturation in a period of 5 weeks. The sheets were then cross evaluated by weight and diameter measurements; quantification of cell density, proliferation, senescence and apoptosis; histomorphometry; gene expression of 48 target genes; and collagen type I protein production. The results revealed very obvious and significant phenotype in A-TSPC sheets characterized by being fragile and thin with poor tissue morphology, and significantly lower cell density and proliferation, but significantly higher levels of the senescence-related gene markers and apoptotic cells. Quantitative gene expression analyses at the mRNA and protein levels, also demonstrated abnormal molecular circuits in the A-TSPC sheets. Taken together, we report for the first time that A-TSPCs exhibit profound deficits in forming 3D tendon tissue organoids, thus making the cell sheet model suitable to investigate the molecular mechanisms involved in tendon aging and degeneration, as well as examining novel pharmacologic strategies for rejuvenation of aged cells.

Changes of Material Elastic Properties during Healing of Ruptured Achilles Tendons Measured with Shear Wave Elastography: A Pilot Study.

Therapy options for ruptured Achilles tendons need to take into account the right balance of timing, amount and intensity of loading to ensure a sufficient biomechanical resilience of the healing tendon on the one hand, and to enable an adequate tensile stimulus on the other hand. However, biomechanical data of human Achilles tendons after rupture during the separate healing stages are unknown. Shear wave elastography is an ultrasound technique that measures material elastic properties non-invasively, and was proven to have a very good correlation to biomechanical studies. Taking advantage of this technology, 12 patients who suffered from an acute Achilles tendon rupture were acquired and monitored through the course of one year after rupture. Nine of these patients were treated non-operatively and were included for the analysis of biomechanical behaviour. A significant increase of material elastic properties was observed within the first six weeks after trauma (up to 80% of baseline value), where it reached a plateau phase. A second significant increase occurred three to six months after injury. This pilot study suggests a time correlation of biomechanical properties with the biological healing phases of tendon tissue. In the reparative phase, a substantial amount of biomechanical resilience is restored already, but the final stage of biomechanical stability is reached in the maturation phase. These findings can potentially be implemented into treatment and aftercare protocols.

Early Functional Rehabilitation after Meniscus Surgery: Are Currently Used Orthopedic Rehabilitation Standards Up to Date?

Meniscus therapy is a challenging process. Besides the respective surgical procedure such as partial meniscectomy, meniscus repair, or meniscus replacement, early postoperative rehabilitation is important for meniscus regeneration and return to sport and work as well as long-term outcome. Various recommendations are available. However, the current literature lacks information concerning the actual early rehabilitation in daily routine recommended by orthopedic surgeons. Thus, the purpose of this study was to investigate currently used standard early rehabilitation protocols in the daily routine of orthopedic surgeons. This study investigated the recommendations and concepts for early rehabilitation after meniscus therapy given by German, Austrian, and Swiss orthopedic institutions. Standardized criteria such as weight bearing, range of motion, use of an orthosis, and rehabilitation training were analyzed according to the conducted surgical procedure: partial meniscectomy, meniscus repair, or meniscus replacement. The analysis of standard rehabilitation concepts for partial meniscectomy (n = 15), meniscus repair (n = 54), and meniscus replacement (n = 7) showed significantly earlier functional rehabilitation in all criteria after partial meniscectomy in contrast to meniscus repair techniques (p < 0.001). In addition, significant restrictions were found in full weight bearing, full range of motion, and the use of braces. In summary, a wide range of recommendations for weight bearing, ROM, brace therapy, and mobilization is available, particularly after meniscus repair and meniscus replacement. Most concepts are in accordance with those described in the current literature. Further research is necessary to enhance the scientific evidence on currently used early rehabilitation concepts after meniscus therapy.

Spectrum of Tendon Pathologies: Triggers, Trails and End-State.

The biggest compartment of the musculoskeletal system is the tendons and ligaments. In particular, tendons are dense tissues connecting muscle to bone that are critical for the integrity, function and locomotion of this system. Due to the increasing age of our society and the overall rise in engagement in extreme and overuse sports, there is a growing prevalence of tendinopathies. Despite the recent advances in tendon research and due to difficult early diagnosis, a multitude of risk factors and vague understanding of the underlying biological mechanisms involved in the progression of tendon injuries, the toolbox of treatment strategies remains limited and non-satisfactory. This review is designed to summarize the current knowledge of triggers, trails and end state of tendinopathies.

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.

Bone Marrow Aspirate Concentrate for the Treatment of Avascular Meniscus Tears in a One-Step Procedure-Evaluation of an In Vivo Model.

Avascular meniscus tears show poor intrinsic regenerative potential. Thus, lesions within this area predispose the patient to developing knee osteoarthritis. Current research focuses on regenerative approaches using growth factors or mesenchymal stem cells (MSCs) to enhance healing capacity within the avascular meniscus zone. The use of MSCs especially as progenitor cells and a source of growth factors has shown promising results. However, present studies use bone-marrow-derived BMSCs in a two-step procedure, which is limiting the transfer in clinical praxis. So, the aim of this study was to evaluate a one-step procedure using bone marrow aspirate concentrate (BMAC), containing BMSCs, for inducing the regeneration of avascular meniscus lesions. Longitudinal meniscus tears of 4 mm in size of the lateral New Zealand White rabbit meniscus were treated with clotted autologous PRP (platelet-rich plasma) or BMAC and a meniscus suture or a meniscus suture alone. Menisci were harvested at 6 and 12 weeks after initial surgery. Macroscopical and histological evaluation was performed according to an established Meniscus Scoring System. BMAC significantly enhanced regeneration of the meniscus lesions in a time-dependent manner and in comparison to the PRP and control groups, where no healing could be observed. Treatment of avascular meniscus lesions with BMAC and meniscus suturing seems to be a promising approach to promote meniscus regeneration in the avascular zone using a one-step procedure.

Partial Anterior Cruciate Ligament Ruptures: Advantages by Intraligament Autologous Conditioned Plasma Injection and Healing Response Technique-Midterm Outcome Evaluation.

The historical treatment options for partial anterior cruciate ligament (ACL) ruptures were conservative therapy or ACL reconstruction by injured bundle or entire ACL replacement. In awareness of the regenerative potential of biologic agents such as mesenchymal stem cells or platelet rich plasma (PRP), the healing response technique was developed to preserve the injured ACL with better outcomes than the conservative therapy. Further improvement of this technique seems to be obtained by the additional application of PRP products. Thus, the aim of this study was to evaluate the midterm outcome after intraligament autologous conditioned plasma (ACP) by a clinical, scoring, and functional performance assessment. 42 patients were evaluated in this study. The failure rate was 9.5%. Outcome evaluation showed good to excellent results. The scores were IKDC subjective 83.2 (SD 14.5), Lysholm 85.5 (SD 15.5), Tegner 4.7 (SD 1.7), and Cincinnati 85.4 (SD 15.5) after a mean follow-up of 33 months. Clinical examination showed stable Lachman test, negative pivot shift phenomenon, and a significant reduction in AP-laxity compared to preoperative status (rolimeter preoperative: 1.9 (SD1.4); postoperative 0.6 (SD1.8), p=0.001) in all patients. Functional performance testing showed no significant differences between the injured and healthy side. Return to sport was achieved after a mean of 5.8 months (SD 3.6) in 71.1% of the included patients. In summary, this new treatment option revealed in midterm follow-up promising results to treat partial ACL lesions with a reduced need for conversion to ACL reconstruction and with a high percentage of return to preinjury sport activity.

In Vitro Comparison of 2D-Cell Culture and 3D-Cell Sheets of Scleraxis-Programmed Bone Marrow Derived Mesenchymal Stem Cells to Primary Tendon Stem/Progenitor Cells for Tendon Repair.

The poor and slow healing capacity of tendons requires novel strategies to speed up the tendon repair process. Hence, new and promising developments in tendon tissue engineering have become increasingly relevant. Previously, we have established a tendon progenitor cell line via ectopic expression of the tendon-related basic helix-loop-helix (bHLH) transcription factor Scleraxis (Scx) in human bone marrow mesenchymal stem cells (hMSC-Scx). The aim of this study was to directly compare the characteristics of hMSC-Scx cells to that of primary human tendon stem/progenitors cells (hTSPCs) via assessment of self-renewal and multipotency, gene marker expression profiling, in vitro wound healing assay and three-dimensional cell sheet formation. As expected, hTSPCs were more naive than hMSC-Scx cells because of higher clonogenicity, trilineage differentiation potential, and expression of stem cell markers, as well as higher mRNA levels of several gene factors associated with early tendon development. Interestingly, with regards to wound healing, both cell types demonstrate a comparable speed of scratch closure, as well as migratory velocity and distance in various migration experiments. In the three-dimensional cell sheet model, hMSC-Scx cells and hTSPCs form compact tendinous sheets as histological staining, and transmission electron microscopy shows spindle-shaped cells and collagen type I fibrils with similar average diameter size and distribution. Taken together, hTSPCs exceed hMSC-Scx cells in several characteristics, namely clonogenicity, multipotentiality, gene expression profile and rates of tendon-like sheet formation, whilst in three-dimensional cell sheets, both cell types have comparable in vitro healing potential and collagenous composition of their three-dimensional cell sheets, making both cell types a suitable cell source for tendon tissue engineering and healing.

Understanding Tendons: Lessons from Transgenic Mouse Models.

Tendons and ligaments are connective tissues that have been comparatively less studied than muscle and cartilage/bone, even though they are crucial for proper function of the musculoskeletal system. In tendon biology, considerable progress has been made in identifying tendon-specific genes (Scleraxis, Mohawk, and Tenomodulin) in the past decade. However, besides tendon function and the knowledge of a small number of important players in tendon biology, neither the ontogeny of the tenogenic lineage nor signaling cascades have been fully understood. This results in major drawbacks in treatment and repair options following tendon degeneration. In this review, we have systematically evaluated publications describing tendon-related genes, which were studied in depth and characterized by using knockout technologies and the subsequently generated transgenic mouse models (Tg) (knockout mice, KO). We report in a tabular manner, that from a total of 24 tendon-related genes, in 22 of the respective knockout mouse models, phenotypic changes were detected. Additionally, in some of the models it was described at which developmental stages these changes appeared and progressed. To summarize, only loss of Scleraxis and TGFß signaling led to severe tendon developmental phenotypes, while mice deficient for various proteoglycans, Mohawk, EGR1 and 2, and Tenomodulin presented mild phenotypes. These data suggest that the tendon developmental system is well organized, orchestrated, and backed up; this is even more evident among the members of the proteoglycan family, where the compensatory effects are much clearer. In future, it will be of great importance to discover additional master tendon transcription factors and the genes that play crucial roles in tendon development. This would improve our understanding of the genetic makeup of tendons, and will increase the chances of generating tendon-specific drugs to advance overall treatment strategies.

Tissue Engineering of Large Full-Size Meniscus Defects by a Polyurethane Scaffold: Accelerated Regeneration by Mesenchymal Stromal Cells.

The endogenous healing potential of avascular meniscal lesions is poor. Up to now, partial meniscectomy is still the treatment of choice for meniscal lesions within the avascular area. However, the large loss of meniscus substance predisposes the knee for osteoarthritic changes. Tissue engineering techniques for the replacement of such lesions could be a promising alternative treatment option. Thus, a polyurethane scaffold, which is already in clinical use, loaded with mesenchymal stromal cells, was analyzed for the repair of critical meniscus defects in the avascular zone. Large, approximately 7 mm broad meniscus lesions affecting both the avascular and vascular area of the lateral rabbit meniscus were treated with polyurethane scaffolds either loaded or unloaded with mesenchymal stromal cells. Menisci were harvested at 6 and 12 weeks after initial surgery. Both cell-free and cell-loaded approaches led to well-integrated and stable meniscus-like repair tissue. However, an accelerated healing was achieved by the application of mesenchymal stromal cells. Dense vascularization was detected throughout the repair tissue of both treatment groups. Overall, the polyurethane scaffold seems to promote the vessel ingrowth. The application of mesenchymal stromal cells has the potential to speed up the healing process.

Boosting tendon repair: interplay of cells, growth factors and scaffold-free and gel-based carriers.

BACKGROUND: Tendons are dense connective tissues and critical components for the integrity and function of the musculoskeletal system. Tendons connect bone to muscle and transmit forces on which locomotion entirely depends. Due to trauma, overuse and age-related degeneration, many people suffer from acute or chronic tendon injuries. Owing to their hypovascularity and hypocellularity, tendinopathies remain a substantial challenge for both clinicians and researchers. Surgical treatment includes suture or transplantation of autograft, allograft or xenograft, and these serve as the most common technique for rescuing tendon injuries. However, the therapeutic efficacies are limited by drawbacks including inevitable donor site morbidity, poor graft integration, adhesion formations and high rates of recurrent tearing. This review summarizes the literature of the past 10 y concerning scaffold-free and gel-based approaches for treating tendon injuries, with emphasis on specific advantages of such modes of application, as well as the obtained results regarding in vitro and in vivo tenogenesis. RESULTS: The search was focused on publications released after 2006 and 83 articles have been analysed. The main results are summarizing and discussing the clear advantages of scaffold-free and hydrogels carriers that can be functionalized with cells alone or in combination with growth factors. CONCLUSION: The improved understanding of tissue resident adult stem cells has made a significant progress in recent years as well as strategies to steer their fate toward tendon lineage, with the help of growth factors, have been identified. The field of tendon tissue engineering is exploring diverse models spanning from hard scaffolds to gel-based and scaffold-free approaches seeking easier cell delivery and integration in the site of injury. Still, the field needs to consider a multifactorial approach that is based on the combination and fine-tuning of chemical and biomechanical stimuli. Taken together, tendon tissue engineering has now excellent foundations and enters the period of precision and translation to models with clinical relevance on which better treatment options of tendon injuries can be shaped up.

Anatomical and radiological evaluation of less invasive stabilisation system (LISS) in correlation with knee lateral collateral ligament insertion.

INTRODUCTION: The Less Invasive Stabilisation System (LISS) is an angle-stable plate that enables treatment of distal femoral comminuted and periprosthetic fracture. As it is placed through a minimally-invasive lateral approach, lateral knee pain is a commonly described symptom after its application. This study investigates knee lateral collateral ligament (LCL) iatrogenic injury during LISS plate fixation. A cadaver study was performed and a retrospective radiological investigation with the analysis of its clinical application was conducted to evaluate possible knee LCL damage. METHODS: The cadaver study included 13 human lower extremities, treated with LISS. After application, lateral knee side was dissected, implants were removed and distances between the drill holes and LCL origin were measured. In the retrospective radiological evaluation, postoperative X-rays for patients treated with distal femoral LISS plate in the University Hospital Regensburg, Germany from January 2010 to December 2015 were examined. Following a protocol described by Pietrini et al., the LCL origin on postoperative X-rays was calculated, both in lateral and anterior-posterior (AP) view, and distances between the plate and its closest locking screw to the LCL origin were measured. RESULTS: In the cadaver study, the mean distance between the closest drilling hole and the ligament origin was 14.0mm (range 9-21mm; SD 3.8mm). Twenty-two patients matched the inclusion criteria for the retrospective radiological study. In lateral view, the mean distance between the origin and the closest locking screw was 6.3mm (range 0-16.4mm; SD 4.7mm); the mean distance between the origin and the plate was 3.1mm (range 0-13.9mm; SD 4.1mm). In AP view, the mean distance between LCL origin and the nearest screw was 2.4mm (range 0-7.6mm; SD 2.4mm). The mean distance between the origin and the most distal locking screw was 9.2mm (range 0-17.5mm; SD 4.0mm). DISCUSSION: The LISS is a safe option to treat distal femoral fractures in respect to the LCL. Due to close proximity, the LCL might be harmed; therefore, lateral knee pain or lateral instability after implantation should be assessed in further treatment.

Autologous mesenchymal stem cells or meniscal cells: what is the best cell source for regenerative meniscus treatment in an early osteoarthritis situation?

BACKGROUND: Treatment of meniscus tears within the avascular region represents a significant challenge, particularly in a situation of early osteoarthritis. Cell-based tissue engineering approaches have shown promising results. However, studies have not found a consensus on the appropriate autologous cell source in a clinical situation, specifically in a challenging degenerative environment. The present study sought to evaluate the appropriate cell source for autologous meniscal repair in a demanding setting of early osteoarthritis. METHODS: A rabbit model was used to test autologous meniscal repair. Bone marrow and medial menisci were harvested 4 weeks prior to surgery. Bone marrow-derived mesenchymal stem cells (MSCs) and meniscal cells were isolated, expanded, and seeded onto collagen-hyaluronan scaffolds before implantation. A punch defect model was performed on the lateral meniscus and then a cell-seeded scaffold was press-fit into the defect. Following 6 or 12 weeks, gross joint morphology and OARSI grade were assessed, and menisci were harvested for macroscopic, histological, and immunohistochemical evaluation using a validated meniscus scoring system. In conjunction, human meniscal cells isolated from non-repairable bucket handle tears and human MSCs were expanded and, using the pellet culture model, assessed for their meniscus-like potential in a translational setting through collagen type I and II immunostaining, collagen type II enzyme-linked immunosorbent assay (ELISA), and gene expression analysis. RESULTS: After resections of the medial menisci, all knees showed early osteoarthritic changes (average OARSI grade 3.1). However, successful repair of meniscus punch defects was performed using either meniscal cells or MSCs. Gross joint assessment demonstrated donor site morbidity for meniscal cell treatment. Furthermore, human MSCs had significantly increased collagen type II gene expression and production compared to meniscal cells (p < 0.05). CONCLUSIONS: The regenerative potential of the meniscus by an autologous cell-based tissue engineering approach was shown even in a challenging setting of early osteoarthritis. Autologous MSCs and meniscal cells were found to have improved meniscal healing in an animal model, thus demonstrating their feasibility in a clinical setting. However, donor site morbidity, reduced availability, and reduced chondrogenic differentiation of human meniscal cells from debris of meniscal tears favors autologous MSCs for clinical use for cell-based meniscus regeneration.