Patient-derived mesenchymal stromal cells (MSCs) play a key role in bone tissue engineering. Various donor-specific factors were identified causing significant variability in the biological properties of MSCs impairing quality of data and inter-study comparability. These limitations might be overcome by pooling cells of different donors. However, the effects of pooling on osteogenic differentiation, proliferation and vitality remain unknown and have, therefore, been evaluated in this study. MSCs of 10 donors were cultivated and differentiated into osteogenic lineage individually and in a pooled setting, containing MSCs of each donor in equal parts. Proliferation was evaluated in expansion (assessment of generation time) and differentiation (quantification of dsDNA content) conditions. Vitality was visualized by a fluorescence-microscopy-based live/dead assay. Osteogenic differentiation was assessed by quantification of alkaline phosphatase (ALP) activity and extracellular calcium deposition. Compared to the individual setting, generation time of pooled MSCs was shorter and proliferation was increased during differentiation with significantly lower variances. Calcium deposition was comparable, while variances were significantly higher in the individual setting. ALP activity showed high variance in both groups, but increased comparably during the incubation period. In conclusion, MSC pooling helps to compensate donor-dependent variability and does not negatively influence MSC vitality, proliferation and osteogenic differentiation.

Standard treatment for bone defects is the biological reconstruction using autologous bone—a therapeutical approach that suffers from limitations such as the restricted amount of bone available for harvesting and the necessity for an additional intervention that is potentially followed by donor-site complications. Therefore, synthetic bone substitutes have been developed in order to reduce or even replace the usage of autologous bone as grafting material. This structured review focuses on the question whether calcium phosphates (CaPs) and bioactive glasses (BGs), both established bone substitute materials, show improved properties when combined in CaP/BG composites. It therefore summarizes the most recent experimental data in order to provide a better understanding of the biological properties in general and the osteogenic properties in particular of CaP/BG composite bone substitute materials. As a result, BGs seem to be beneficial for the osteogenic differentiation of precursor cell populations in-vitro when added to CaPs. Furthermore, the presence of BG supports integration of CaP/BG composites into bone in-vivo and enhances bone formation under certain circumstances.

As unilateral cerebral palsy represents a complex disorder, gait classification is difficult. Knowledge of the most frequent gait patterns and functional impairment is crucial for proper decision-making. This study analyzes the prevalence of gait patterns as well as the relation of different gait patterns and the Gross Motor Function Classification System (GMFCS). Eighty-nine patients were classified retrospectively using the GMFCS, the classification of Winters, Gage, and Hicks (WGH), and Sutherland et al. The distribution of GMFCS levels among the different gait patterns was analyzed using Chi-squared test. The most common subtypes were GMFCS level I, WGH type I, and recurvatum knee. Seventeen percent (WGH) and 59% (Sutherland) of the patients did not match any criteria. Applying both classifications complementarily reduced the number of unclassified patients significantly. There was no significant difference concerning the distribution of GMFCS levels or age among the different gait patterns. A combined use of various classification systems is beneficial for proper decision-making. Unclassified patients seem to be a heterogeneous subgroup concerning functional impairment. There is a need of further characterization of the unclassifiable gait patterns and the caused functional impairment. Instrumented gait analysis remains the gold standard and should be broadly used for future studies and in clinical practice.

A variety of gait pathologies is seen in cerebral palsy. Movement patterns between different levels of functional impairment may differ. The objective of this work was the evaluation of Gross Motor Function Classification System (GMFCS) level-specific movement disorders. A total of 89 individuals with unilateral cerebral palsy and no history of prior treatment were included and classified according to their functional impairment. GMFCS level-specific differences, kinematics and joint moments, exclusively of the involved side, were analyzed for all planes for all lower limb joints, including pelvic and trunk movements. GMFCS level I and level II individuals most relevantly showed equinus/reduced dorsiflexion moments, knee flexion/reduced knee extension moments, reduced hip extension moments with pronounced flexion, internal hip rotation and reduced hip abduction. Anterior pelvic tilt, obliquity and retraction were found. Individuals with GMFCS level II were characterized by an additional pronounced reduction in all extensor moments, pronounced rotational malalignment and reduced hip abduction. The most striking characteristics of GMFCS level II were excessive anterior pelvic/trunk tilt and excessive trunk obliquity. Pronounced reduction in extensor moments and excessive trunk lean are distinguishing features of GMFCS level II. These patients would benefit particularly from surgical treatment restoring pelvic symmetry and improving hip abductor leverage. Future studies exploring GMFCS level-specific compensation of the sound limb and GMFCS level-specific malalignment are of interest.

Purpose: To determine the Patient Acceptable Symptomatic State (PASS) thresholds for the Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), Lysholm and EuroQol 5 Dimensions (EQ‐5D) scores and to identify predictors of PASS at 10 years after matrix‐associated autologous chondrocyte implantation (M‐ACI). Methods: Patients who underwent M‐ACI for chondral defects of the knee between 2011 and 2015 were prospectively evaluated. KOOS, IKDC, Lysholm and EQ‐5D scores and anchor‐based questions were assessed at baseline and at least 10 years post‐operatively. PASS thresholds were determined using receiver operating characteristic (ROC) curve analyses. Multivariable binomial regression analysis was performed to determine the effect of sex, body mass index (BMI), articular cartilage maturation status and the presence of more than one previous knee surgery on the likelihood of achieving PASS. Results: A total of 112 patients who met the inclusion criteria were evaluated at a mean of 11.3 ± 1.2 years post‐operatively, with a mean age of 29.2 ± 11.0 years. The PASS thresholds for the aforementioned PROMs at 10 years were 61.9 for KOOS (Symptoms 51.8, Pain 79.2, Activities of Daily Living 87.5, Sport 57.5 and Quality of Life 59.4), 59.7 for IKDC, 61.5 for Lysholm and 82.5 for EQ‐5D. The ROC curve showed good to excellent predictive value with an area under the curve (AUC) of 0.76–0.84. Male gender (odds ratio [OR] = 3.1; p = 0.016) and BMI between 20 and 29 (OR = 3.9; p = 0.004) had a positive predictive value for achieving PASS at long‐term follow‐up. Conclusions: The present study determined long‐term PASS thresholds for KOOS, IKDC, Lysholm and EQ‐5D scores in patients undergoing M‐ACI for cartilage repair at the knee. Male gender and a BMI of 20–29 were positive predictors of the likelihood of achieving PASS at 10 years. The identified PASS thresholds are critical for assessing clinical outcomes, evaluating procedural efficacy for regulatory considerations, and planning sample sizes for prospective, controlled studies. Level of Evidence: Level IV.