Osteoarthritis (OA) is a common cause of chronic pain and disability. Regenerative therapies using mesenchymal stem cells (MSCs) provide an option for OA treatment as it could potentially regenerate the damaged cartilage. Bone marrow, adipose tissue and synovium are common MSC sources. The aim is to compare the therapeutic effect of MSCs from bone marrow, adipose tissue and synovium; combining its differentiation potential and accessibility, to decide the optimal source of MSCs for the treatment of knee OA. A comparison of preclinical and clinical studies using MSCs has been made with regard to treatment outcomes, isolation procedure and differentiation potential. All types of MSCs are effective at improving the clinical and structural condition of OA patients, but the longevity of the treatment, i.e. an effect that is maintained for at least 2 years, cannot be guaranteed. This review highlighted great variations in selection criteria and culture expansion conditions of MSCs between the literature and clinical trials. It also emphasised a substantial diversity and lack of consistency in the assessment mythology of clinical outcome after completion of MSC therapies procedures. A more cohesive methodology is required to evaluate the outcome of MSC treatments using quantitative and standardised frameworks in order to be able to directly compare results. Larger population of patients are recommended to assess the quality of MSC when designing studies and clinical trials to reaffirm the efficacy of MSC treatment prior to and within the clinical trials and follow up studies.

This work presents a combined experimental–numerical framework for the biomechanical characterization of highly hydrated collagen hydrogels, namely with 0.20, 0.30 and 0.40 % (by weight) of collagen concentration. Collagen is the most abundant protein in the extracellular matrix of animals and humans. Its intrinsic biocompatibility makes collagen a promising substrate for embedding cells within a highly hydrated environment mimicking natural soft tissues. Cell behaviour is greatly influenced by the mechanical properties of the surrounding matrix, but the biomechanical characterization of collagen hydrogels has been challenging up to now, since they present non-linear poro-viscoelastic properties. Combining the stiffness outcomes from rheological experiments with relevant literature data on collagen permeability, poroelastic finite element (FE) models were developed. Comparison between experimental confined compression tests available in the literature and analogous FE stress relaxation curves showed a close agreement throughout the tests. This framework allowed establishing that the dynamic shear modulus of the collagen hydrogels is between 0.0097 ± 0.018 kPa for the 0.20 % concentration and 0.0601 ± 0.044 kPa for the 0.40 % concentration. The Poisson’s ratio values for such conditions lie within the range of 0.495–0.485 for 0.20 % and 0.480–0.470 for 0.40 %, respectively, showing that rheology is sensitive enough to detect these small changes in collagen concentration and thus allowing to link rheology results with the confined compression tests. In conclusion, this integrated approach allows for accurate constitutive modelling of collagen hydrogels. This framework sets the grounds for the characterization of related hydrogels and to the use of this collagen parameterization in more complex multiscale models.

Purpose of Review The treatment of non-union fractures represents a significant challenge for orthopaedic surgeons. In recent years, biologic agents have been investigated and utilised to support and improve bone healing. Among these agents, platelet-rich plasma (PRP) is an emerging strategy that is gaining popularity. The aim of this review is to evaluate the current literature regarding the application and clinical effectiveness of PRP injections, specifically for the treatment of non-union fractures. Recent Findings The majority of published studies reported that PRP accelerated fracture healing; however, this evidence was predominantly level IV. The lack of randomised, clinical trials (level I–II evidence) is currently hampering the successful clinical translation of PRP as a therapy for non-union fractures. This is despite the positive reports regarding its potential to heal non-union fractures, when used in isolation or in combination with other forms of treatment. Summary Future recommendations to facilitate clinical translation and acceptance of PRP as a therapy include the need to investigate the effects of administering higher volumes of PRP (i.e. 5–20 mL) along with the requirement for more prolonged (> 11 months) randomised clinical trials.

Establishing how to effectively manufacture cell therapies is an industry-level problem. Decentralised manufacturing is of increasing importance, and its challenges are recognised by healthcare regulators with deviations and comparability issues receiving specific attention from them. This paper is the first to report the deviations and other risks encountered when implementing the expansion of human pluripotent stem cells (hPSCs) in an automated three international site-decentralised manufacturing setting. An experimental demonstrator project expanded a human embryonal carcinoma cell line (2102Ep) at three development sites in France, Germany and the UK using the CompacT SelecT (Sartorius Stedim, Royston, UK) automated cell culture platform. Anticipated variations between sites spanned material input, features of the process itself and production system details including different quality management systems and personnel. Where possible, these were pre-addressed by implementing strategies including standardisation, cell bank mycoplasma testing and specific engineering and process improvements. However, despite such measures, unexpected deviations occurred between sites including software incompatibility and machine/process errors together with uncharacteristic contaminations. Many only became apparent during process proving or during the process run. Further, parameters including growth rate and viability discrepancies could only be determined post-run, preventing 'live' corrective measures. The work confirms the critical nature of approaches usually taken in Good Manufacturing Practice (GMP) manufacturing settings and especially emphasises the requirement for monitoring steps to be included within the production system. Real-time process monitoring coupled with carefully structured quality systems is essential for multiple site working including clarity of decision-making roles. Additionally, an over-reliance upon post-process visual microscopic comparisons has major limitations; it is difficult for non-experts to detect deleterious culture changes and such detection is slow.

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