Patient-oriented and performance-based outcomes after knee autologous chondrocyte implantation: a timeline for the first year of recovery

It is well established that autologous chondrocyte implantation (ACI) can require extended recovery postoperatively; however, little information exists to provide clinicians and patients with a timeline for anticipated function during the first year after ACI. Objective: To document the recovery of functional performance of activities of daily living after ACI. Patients: ACI patients (n = 48, 29 male 35.1 ± 8.0 y). Intervention: All patients completed functional tests (weight-bearing squat, walk-across, sit-to-stand, step-up/over, and forward lunge) using the NeuroCom long force plate (Clackamas, OR) and completed patient-reported outcome measures (International Knee Documentation Committee Subjective Knee Evaluation Form, Lysholm, Western Ontario and McMaster Osteoarthritis Index WOMAC, and 36-Item Short-Form Health Survey) preoperatively and 3, 6, and 12 mo postoperatively. Main Outcome Measures: A covariance pattern model was used to compare performance and self-reported outcome across time and provide a timeline for functional recovery after ACI. Results: Participants demonstrated significant improvement in walk-across stride length from baseline (42.0% ± 8.9% height) at 6 (46.8% ± 8.1%) and 12 mo (46.6% ± 7.6%). Weight bearing on the involved limb during squatting at 30°, 60°, and 90° was significantly less at 3 mo than presurgery. Step-up/over time was significantly slower at 3 mo (1.67 ± 0.69 s) than at baseline (1.49 ± 0.33 s), 6 mo (1.51 ± 0.36 s), and 12 mo (1.40 ± 0.26 s). Step-up/over lift-up index was increased from baseline (41.0% ± 11.3% body weight BW) at 3 (45.0% ± 11.7% BW), 6 (47.0% ± 11.3% BW), and 12 mo (47.3% ± 11.6% BW). Forward-lunge time was decreased at 3 mo (1.51 ± 0.44 s) compared with baseline (1.39 ± 0.43 s), 6 mo (1.32 ± 0.05 s), and 12 mo (1.27 ± 0.06). Similarly, forward-lunge impact force was decreased at 3 mo (22.2% ± 1.4% BW) compared with baseline (25.4% ± 1.5% BW). The WOMAC demonstrated significant improvements at 3 mo. All patient-reported outcomes were improved from baseline at 6 and 12 mo postsurgery. Conclusions: Patients' perceptions of improvements may outpace physical changes in function. Decreased function for at least the first 3 mo after ACI should be anticipated, and improvement in performance of tasks requiring weight-bearing knee flexion, such as squatting, going down stairs, or lunging, may not occur for a year or more after surgery

Innovative Techniques to Enhance Musculoskeletal Surgery Outcomes

n.a. - Editoria

Polymer-based controlled-release fed-batch microtiter plate - diminishing the gap between early process development and production conditions

Background: Fed-batch conditions are advantageous for industrial cultivations as they avoid unfavorable phenomena appearing in batch cultivations. Those are for example the formation of overflow metabolites, catabolite repression, oxygen limitation or inhibition due to elevated osmotic concentrations. For both, the early bioprocess development and the optimization of existing bioprocesses, small-scale reaction vessels are applied to ensure high throughput, low costs and prompt results. However, most conventional small-scale procedures work in batch operation mode, which stands in contrast to fed-batch conditions in large-scale bioprocesses. Extensive expenditure for installations and operation accompany almost all cultivation systems in the market allowing fed-batch conditions in small-scale. An alternative, more cost efficient enzymatic glucose release system is strongly influenced by environmental conditions. To overcome these issues, this study investigates a polymer-based fed-batch system for controlled substrate release in microtiter plates. Results: Immobilizing a solid silicone matrix with embedded glucose crystals at the bottom of each well of a microtiter plate is a suitable technique for implementing fed-batch conditions in microtiter plates. The results showed that the glucose release rate depends on the osmotic concentration, the pH and the temperature of the medium. Moreover, the applied nitrogen source proved to influence the glucose release rate. A new developed mathematical tool predicts the glucose release for various media conditions. The two model organisms E. coli and H. polymorpha were cultivated in the fed-batch microtiter plate to investigate the general applicability for microbial systems. Online monitoring of the oxygen transfer rate and offline analysis of substrate, product, biomass and pH confirmed that fed-batch conditions are comparable to large-scale cultivations. Furthermore, due to fed-batch conditions in microtiter plates, product formation could be enhanced by the factor 245 compared to batch cultivations. Conclusions: The polymer-based fed-batch microtiter plate represents a sophisticated and cost efficient system to mimic typical industrial fed-batch conditions in small-scale. Thus, a more reliable strain screening and early process development can be performed. A systematical scale-down with low expenditure of work, time and money is possible. © 2019 The Author(s)

Polymer-based controlled-release fed-batch microtiter plate - diminishing the gap between early process development and production conditions

Background: Fed-batch conditions are advantageous for industrial cultivations as they avoid unfavorable phenomena appearing in batch cultivations. Those are for example the formation of overflow metabolites, catabolite repression, oxygen limitation or inhibition due to elevated osmotic concentrations. For both, the early bioprocess development and the optimization of existing bioprocesses, small-scale reaction vessels are applied to ensure high throughput, low costs and prompt results. However, most conventional small-scale procedures work in batch operation mode, which stands in contrast to fed-batch conditions in large-scale bioprocesses. Extensive expenditure for installations and operation accompany almost all cultivation systems in the market allowing fed-batch conditions in small-scale. An alternative, more cost efficient enzymatic glucose release system is strongly influenced by environmental conditions. To overcome these issues, this study investigates a polymer-based fed-batch system for controlled substrate release in microtiter plates. Results: Immobilizing a solid silicone matrix with embedded glucose crystals at the bottom of each well of a microtiter plate is a suitable technique for implementing fed-batch conditions in microtiter plates. The results showed that the glucose release rate depends on the osmotic concentration, the pH and the temperature of the medium. Moreover, the applied nitrogen source proved to influence the glucose release rate. A new developed mathematical tool predicts the glucose release for various media conditions. The two model organisms E. coli and H. polymorpha were cultivated in the fed-batch microtiter plate to investigate the general applicability for microbial systems. Online monitoring of the oxygen transfer rate and offline analysis of substrate, product, biomass and pH confirmed that fed-batch conditions are comparable to large-scale cultivations. Furthermore, due to fed-batch conditions in microtiter plates, product formation could be enhanced by the factor 245 compared to batch cultivations. Conclusions: The polymer-based fed-batch microtiter plate represents a sophisticated and cost efficient system to mimic typical industrial fed-batch conditions in small-scale. Thus, a more reliable strain screening and early process development can be performed. A systematical scale-down with low expenditure of work, time and money is possible. © 2019 The Author(s)

The role of Wnt pathway in the pathogenesis of OA and its potential therapeutic implications in the field of regenerative medicine

Introduction. Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation, subchondral damage, and bone remodelling, affecting most commonly weight-bearing joints, such as the knee and hip. The loss of cartilage leads to joint space narrowing, pain, and loss of function which could ultimately require total joint replacement. The Wnt/beta catenin pathway is involved in the pathophysiology of OA and has been proposed as a therapeutic target. Endogenous and pharmacological inhibitors of this pathway were recently investigatedwithin innovative therapies including the use of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs). Methods. A review of the literature was performed on the PubMed database based on the following inclusion criteria: article written in English language in the last 20 years and dealing with (1) the role of Wnt-beta catenin pathway in the pathogenesis of osteoarthritis and (2) pharmacologic or biologic strategies modulating the Wnt-beta catenin pathway in the OA setting. Results. Evidences support that Wnt signalling pathway is likely linked to OA progression and severity. Its inhibition through natural antagonists and new synthetic or biological drugs shares the potential to improve the clinical condition of the patients by affecting the pathological activity of Wnt/beta-catenin signalling. Conclusions. While further research is needed to better understand the mechanisms regulating the molecular interaction between OA regenerative therapies and Wnt, it seems that biologic therapies for OA exert modulation on Wnt/beta catenin pathway that might be relevant in achieving the beneficial clinical effect of those therapeutic strategies

Multimodal nonlinear imaging of atherosclerotic plaques differentiation of triglyceride and cholesterol deposits

Cardiovascular diseases in general and atherothrombosis as the most common of its individual disease entities is the leading cause of death in the developed countries. Therefore, visualization and characterization of inner arterial plaque composition is of vital diagnostic interest, especially for the early recognition of vulnerable plaques. Established clinical techniques provide valuable morphological information but cannot deliver information about the chemical composition of individual plaques. Therefore, spectroscopic imaging techniques have recently drawn considerable attention. Based on the spectroscopic properties of the individual plaque components, as for instance different types of lipids, the composition of atherosclerotic plaques can be analyzed qualitatively as well as quantitatively. Here, we compare the feasibility of multimodal nonlinear imaging combining two-photon fluorescence (TPF), coherent anti-Stokes Raman scattering (CARS) and second-harmonic generation (SHG) microscopy to contrast composition and morphology of lipid deposits against the surrounding matrix of connective tissue with diffraction limited spatial resolution. In this contribution, the spatial distribution of major constituents of the arterial wall and atherosclerotic plaques like elastin, collagen, triglycerides and cholesterol can be simultaneously visualized by a combination of nonlinear imaging methods, providing a powerful label-free complement to standard histopathological methods with great potential for in vivo application

Differential analysis of the impact of lesions’ location on clinical and radiological outcomes after the implantation of a novel aragonite-based scaffold to treat knee cartilage defects

Purpose: There is limited comparative evidence on patient outcomes following cartilage repair in various knee compartments. The aim of this study was to compare clinical and imaging outcomes after treating cartilage defects in femoral condyles and trochlea with either an aragonite-based scaffold or surgical standard of care (SSoC, i.e., debridement/microfractures) in a large multicentre randomized controlled trial. Methods: 247 patients with up to three knee joint surface lesions (ICRS grade IIIa or above) in the femoral condyles, trochlea or both (“mixed”), were enrolled and randomized to surgery with either a cell-free aragonite scaffold or SSoC. Patients were followed for up to 48 months by analysing subjective scores (KOOS and IKDC), radiological outcomes (defect filling on MRI), as well as treatment failure rates and adverse events. A differential analysis of outcomes for condylar, trochlear and mixed lesions was performed. Results: The scaffold group significantly outperformed the SSoC group regardless of lesion location with statistically significantly better KOOS Overall scores at 24 months (all p ≤ 0.0009) and 48 months (all p ≤ 0.02). Similar results were observed for KOOS subscales and IKDC scores. For KOOS responder rates, superiority of the implant group was demonstrated at 24, 36, and 48 months (all p ≤ 0.004). Higher defect filling on MRI for implants was observed for all locations. Lower treatment failure rates for the implant were observed in condylar and mixed lesions. Conclusion: The aragonite-based scaffold was safe and effective regardless of the defect location, providing superior clinical and radiological outcomes compared to SSoC up to four years follow-up. Level of evidence: I – Randomized controlled trial

Seaweed polysaccharide-based hydrogels used for the regeneration of articular cartilage

This manuscript provides an overview of the in vitro and in vivo studies reported in the literature focusing on seaweed polysaccharides based hydrogels that have been proposed for applications in regenerative medicine, particularly, in the field of cartilage tissue engineering. For a better understanding of the main requisites for these specific applications, the main aspects of the native cartilage structure, as well as recognized diseases that affect this tissue are briefly described. Current available treatments are also presented to emphasize the need for alternative techniques. The following part of this review is centered on the description of the general characteristics of algae polysaccharides, as well as relevant properties required for designing hydrogels for cartilage tissue engineering purposes. An in-depth overview of the most well known seaweed polysaccharide, namely agarose, alginate, carrageenan and ulvan biopolymeric gels, that have been proposed for engineering cartilage is also provided. Finally, this review describes and summarizes the translational aspect for the clinical application of alternative systems emphasizing the importance of cryopreservation and the commercial products currently available for cartilage treatment.Authors report no declarations of interest. Authors thank the Portuguese Foundation for Science and Technology (FCT) for the PhD fellowship of Elena G. Popa (SFRH/BD/64070/2009) and research project (MIT/ECE/0047/2009). The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no REGPOT-CT2012-316331-POLARIS

Osteointegration of soft tissue grafts within the bone tunnels in anterior cruciate ligament reconstruction can be enhanced

Anterior cruciate ligament reconstruction with a soft tissue autograft (hamstring autograft) has grown in popularity in the last 10 years. However, the issues of a relatively long healing time and an inferior histological healing result in terms of Sharpey-like fibers connection in soft tissue grafts are still unsolved. To obtain a promising outcome in the long run, prompt osteointegration of the tendon graft within the bone tunnel is essential. In recent decades, numerous methods have been reported to enhance osteointegration of soft tissue graft in the bone tunnel. In this article, we review the current literature in this research area, mainly focusing on strategies applied to the local bone tunnel environment. Biological strategies such as stem cell and gene transfer technology, as well as the local application of specific growth factors have been reported to yield exciting results. The use of biological bone substitute and physical stimulation also obtained promising results. Artificially engineered tissue has promise as a solution to the problem of donor site morbidity. Despite these encouraging results, the current available evidence is still experimental. Further clinical studies in terms of randomized control trial in the future should be conducted to extrapolate these basic science study findings into clinical practice. © 2009 Springer-Verlag.postprin