Regeneration of the elbow joint in the developing chick embryo recapitulates development.

Synovial joints are among the most important structures that give us complex motor abilities as humans. Degenerative joint diseases, such as arthritis, cause loss of normal joint functioning and affect over 40 million people in the USA and approximately 350 million people worldwide. Therapies based on regenerative medicine hold the promise of effectively repairing or replacing damaged joints permanently. Here, for the first time, we introduce a model for synovial joint regeneration utilizing the chick embryo. In this model, a block of tissue that contains the prospective elbow is excised, leaving a window with strips of anterior and posterior tissue intact (window excision, WE). In contrast, we also slice out the same area containing the elbow and the distal piece of the limb is pinned back onto the stump (slice excision, SE). Interestingly, when the elbow is removed via WE, regeneration of the joint takes place, whereas the elbow joint does not regenerate following SE. In order to investigate whether the regeneration response recapitulates the developmental program of forming joints, we used GDF-5 and Autotaxin (Atx) as joint tissue specific markers, and Sox-9 and Col-9 as cartilage markers for in situ hybridization on sections at different time points after WE and SE surgeries. Re-expression of GDF-5 and Atx is observed in the WE samples by 60h after surgery. In contrast, the majority of the samples that underwent SE surgery did not express GDF-5 and Atx. Also, in SE fusion of cartilage elements takes place and the joint interzone does not form. This is indicated by continuous Col-9 expression in SE limbs, whereas Col-9 is downregulated at the joint interzone in the regenerating WE samples. This order and pattern of gene expression observed in regenerates is similar to the development of a joint suggesting that regeneration recapitulates development at the molecular level. This model defines some of the conditions required for inducing joint regeneration in an otherwise nonregenerating environment. This knowledge can be useful for designing new therapeutic approaches for joint loss or for conditions affecting joint integrity in humans.

Three-Dimensional Printed Patient Models for Complex Pediatric Spinal Surgery.

Background: Pediatric spinal deformity surgeries are challenging operations that require considerable expertise and resources. The unique anatomy and rarity of these cases present challenges in surgical training and preparation. We present a case series illustrating how 3-dimensional (3-D) printed models were used in preoperative planning for 3 cases of pediatric spinal deformity surgery. Case Series: Patient 1 was a 6-year-old male with scoliosis secondary to an L3 hemivertebra and severe congenital heart disease who underwent excision of the L3 hemivertebra and L2-L4 spinal fusion. Patient 2 was an 11-year-old male with an L2 hemivertebra and lumbar kyphosis who underwent excision of the L2 hemivertebra and T12-L4 spinal fusion. Patient 3 was a 6-year-old female with Down syndrome who presented with atlantoaxial instability and acute lymphoblastic leukemia. She underwent occipital-cervical spinal fusion and decompression. Prior to surgery, 3-D printed models of the patients' spines were created based on computed tomography (CT) imaging. Conclusion: The anatomic complexity and risk of devastating neurologic consequences in spine surgery call for careful preparations. 3-D models enable more efficient and precise surgical planning compared to the use of 2-dimensional CT/magnetic resonance images. The 3-D models also make it easier to visualize patient anatomy, allowing patients and their families who lack medical training to interpret and understand cross-sectional anatomy, which in our experience, enhanced the consultations.