The reliable production of _in vitro_ chondrocytes that faithfully recapitulate _in vivo_ development would be of great benefit for orthopaedic disease modelling and regenerative therapy(1,2). Current efforts are limited by off-target differentiation, resulting in a heterogeneous product, and by the lack of comparison to human tissue, which precludes detailed evaluation of _in vitro_ cells(3,4). We performed single-cell RNA-sequencing of long bones dissected from first-trimester fetal limbs to form a detailed ‘atlas’ of endochondral ossification. Through 100-gene in-situ sequencing, we placed each sequenced cell type into its anatomical context to spatially resolve the process of endochondral ossification. We then used this atlas to perform deconvolution on a series of previously published bulk transcriptomes generated from _in vitro_ chondrogenesis protocols to evaluate their ability to accurately produce chondrocytes. We then applied single-nuclear RNA-sequencing to cells from the best performing protocol collected at multiple time points to allow direct comparison between the differentiation of _in vitro_ and _in vivo_ cells. We captured 275,000 single fetal cells, profiling the development of chondrocytes from multipotent mesenchymal progenitors to hypertrophic cells at full transcriptomic breadth. Using this atlas as the ground truth for evaluating _in vitro_ cells, we found substantial variability in cell states produced by each protocol, with many showing little similarity to _in vivo_ cells, and all exhibiting off-target differentiation. Trajectory alignment between _in vivo_ and _in vitro_ single-cell data revealed key differences in gene expression dynamics between _in vitro_ and _in vivo cells,_ with several osteoblastic transcription factors erroneously unregulated _in vitro,_ including _FOXO1._. Using this information, we inhibited _FOXO1_ in culture to successfully increase chondrocyte yield _in vitro._. This study presents a new framework for evaluating tissue engineering protocols, using single-cell data to drive improvement and bring the prospect of true engineered cartilage closer to reality

The purpose of this study was to investigate the development of the osseous acetabular index (OAI) and cartilaginous acetabular index (CAI) using MRI. The OAI and CAI were measured on the coronal MR images of the hip in 81 children with developmental dysplasia of the hip (DDH), with a mean age of 19.6 months (3 to 70), and 241 normal control children with a mean age of 5.1 years (1 month to 12.5 years). Additionally the developmental patterns of the OAI and CAI in normal children were determined by age-based cross-sectional analysis.

Unlike the OAI, the normal CAI decreased rapidly from a mean of 10.17° (sd 1.60) to a mean of 8.25° (sd 1.90) within the first two years of life, and then remained constant at a mean of 8.04° (sd 1.65) until adolescence. Although no difference in OAI was found between the uninvolved hips in children with unilateral DDH and normal hips (p = 0.639), the CAI was significantly different between them both (p < 0.001). The normal CAI has fully formed at birth, and is maintained constantly throughout childhood. The CAI in the unaffected hips in children with unilateral DDH is also mildly dysplastic.

Objectives

The purpose of this study was to investigate whether the femoral head–neck contour, characterised by the alpha angle, varies with the stage of physeal maturation using MRI evaluation of an asymptomatic paediatric population.