Traumatic acute or chronic tendon injuries are a wide clinical problem in modern society, resulting in important economic burden to the health system and poor quality of life in patients. Due to the low cellularity and vascularity of tendon tissue the repair process is slow and inefficient, resulting in mechanically, structurally, and functionally inferior tissue. Tissue engineering and regenerative medicine are promising alternatives to the natural healing process for tendon repair, especially in the reconstruction of large damaged tissues. The aim of TRITONE project is to develop a smart, bioactive implantable 3D printed scaffold, able to reproduce the structural and functional properties of human tendon, using FDA approved materials and starting from MSC and their precursor, MPC cell mixtures from human donors. Total cohort selected in the last 12 months was divided in group 1 (N=20) of subjects with tendon injury and group 2 (N=20) of healthy subject. Groups were profiled and age and gender matched. Inclusion criteria were age>18 years and presence of informed consent. Ongoing pregnancy, antihypertensive treatment, cardiovascular diseases, ongoing treatment with anti-aggregants, acetylsalicylic-acid or lithium and age<18 years were exclusion criteria. Firstly, we defined clinical, biological, nutritional life style and genetic profile of the cohort. The deficiency of certain nutrients and sex hormonal differences were correlated with tendon-injured patients. It was established the optimal amount of MPC/MSC human cell (collected from different patients during femoral neck osteotomy). Finally, most suitable biomaterials for tendon regeneration and polymer tendon-like structure were identified. Hyaluronic acid, chemical surface and soft-molecular imprinting (SOFT-MI) was used to functionalize the scaffold. These preliminary results are promising. It will be necessary to enroll many more patients to identify genetic status connected with the onset of tendinopathy. The functional and structural characterization of smart bioactive tendon in dynamic environment will represent the next project step

Introduction. Congenital scoliosis is a prevalent congenital spinal deformity, more frequently encountered than congenital lordosis or kyphosis. The prevailing belief is that most instances of congenital scoliosis are not hereditary but rather stem from issues in fetal spine development occurring between the 5th and 8th weeks of pregnancy. However, it has been linked to several genes in current literature. Our goal was to explore potential pathways through an exhaustive bioinformatics analysis of genes related to congenital scoliosis. Method. The literature from the 1970s to February 2024 was surveyed for genes associated with CS, and 63 genes were found to be associated with AIS out of 1743 results. These genes were analyzed using DAVID Bioinformatics. Result. Our pathway analysis has unveiled several significant associations with congenital scoliosis. Notably, “Glycosaminoglycan biosynthesis - chondroitin sulfate / dermatan sulfate” (P-Value:8.8E-3, Fold Enrichment: 20.6), “Central carbon metabolism in cancer” (P-Value:1.3E-3, Fold Enrichment: 10.3), and “Lysine degradation” (P-Value: 9.0E-3, Fold Enrichment: 9.1) emerge as statistically significant pathways. Additionally, “Endocrine resistance” (P-Value:4.4E-3, Fold Enrichment:7.4) and”EGFR tyrosine kinase inhibitor resistance” (P-Value: 1.7E-2, Fold Enrichment:7.3) pathways are noteworthy. These findings suggest a potential involvement of these pathways in the biological processes underlying congenital scoliosis. Furthermore, “Signaling pathways regulating pluripotency of stem cells” (P-Value:4.0E-4, Fold Enrichment:7.1), “Notch signaling pathway” (P-Value:6.7E-2, Fold Enrichment: 7.0), and “TGF-beta signaling pathway” (P-Value:6.2E-3, Fold Enrichment: 6.7) exhibit a less pronounced yet intriguing association that may warrant further investigation. Conclusion. In conclusion, our comprehensive analysis of the genetic etiology of congenital scoliosis has revealed significant associations with various pathways, shedding light on potential underlying biological mechanisms. While further research is needed to fully understand these associations and their implications, our findings provide a valuable starting point for future investigations into the management and treatment of congenital scoliosis

Purpose. Ultrasound of the neonatal and infantile hip is a useful tool in diagnosis and treatment of the developmental dysplasia of the hip (DDH), especially given the fact that numerous cases of DDH do not present any findings in the clinical examination. Methods. Between January 2014 and May 2020, 10536 (5273 neonates and infants, 53% girls, 47% boys) consecutive neonatal and infantile hip joints were studied using the Graf Hip Ultrasound method. Results. 607 hips were diagnosed as abnormal. 523 (5%) hip joints were type IIA, 18 (0.17%) were type ΙΙΒ, 19 (0.18%) were type ΙΙC, 33 (0.31%) were type ΙΙΙ and 14 (0.13%) were type IV. 72% of patients were girls, 55% of patients were firstborns, 35,7% presented breech, 8,2% had a positive family history of DDH, 6% were part of a multiple pregnancy, while 27,2% had no predisposing factor for the disease. Type ΙΙΑ hips were treated with follow- up only and had all matured (turned to normal- type I hips) within a trimester. Type ΙΙΒ και ΙΙC hips were treated using an abductor harness and were normal (type I) within three months. 35.7% of type ΙΙΙ were treated with an abductor harness and 64.3% with hip spica. All type IV hips were treated with hip spica. The duration of therapy for type III and type IV hips was 3 months. Conclusion. The early use of a hip ultrasound provides us with the ability to diagnose and treat DDH efficiently, resulting in a normal hip joint within the first months of life

Summary Statement. Mesenchymal stem cells from minced umbilical cord fragments may represent a valuable cell population for cartilage and bone tissue engineering. Introduction. A promising approach for cartilage and bone repair is the use of umbilical cord mesenchymal stem cell (UC-MSC)-based tissue engineering. Through a simple and efficient protocol based on mincing the umbilical cord, a consistent number of multipotent UC-MSCs can be obtained. The aim of this in-vitro study is to investigate the pluripotency of UC-MSCs and, in particular, the chondrogenic and osteogenic potential of UC-MSCs grown in tridimensional scaffold, in order to identify a potential clinical relevance for patients who might benefit from MSCs-therapy. Materials/Methods. Fresh UC samples from women with healthy pregnancies were retrieved at the end of caesarean deliveries. The UC samples were manually minced without any enzymatic digestion into very small fragments (less than 4 mm length) and cultivated in an MSC expansion medium. At day 14, the UC tissue was removed and adherent cells were allowed to expand for 2 additional weeks. At day 28, the adherent cells were collected and replated until confluence was reached (Passage 1 or P1). Immunophenotypic characterization, Fluorescence In Situ Hybridization (FISH), telomere length analysis, Immunosuppression of T lymphocyte cultures, and multilineage differentiation was performed in UC-MSCs at P1 or P2. For chondrogenic differentiation on scaffold, UC-MSCs at P2 were loaded either on a hyaluronic-acid (HA)-felt(Hyaff-11) or on a collagen-I/III membrane(Chondro-gide), with a coating of fibrin glue(Tisseel), and grown in chondrogenic medium both in normoxic and hypoxic(10%O. 2. ) conditions. After 1 month, sections were stained with haematoxylin/eosin and Safranin-O. Expression of chondrocyte markers(sox-9, type II collagen) and hypoxic markers(HIFs) was assessed using immunofluorescence(IF). For osteogenic differentiation on scaffold, UC-MSCs at P2 were loaded into a bone-graft-substitute(Orthoss) and grown in osteogenic medium. After 10, 20,30 days, sections were stained with haematoxylin/eosin and expression of osteocalcin and RunX2 was assessed using immunofluorescence. Results. At P1, we obtained a mean value of 22.8 × 10. 6. cells(SD 1.7) from each UC, corresponding to 0.66 (SD 0.14) × 10. 6. cells/gram of UC. Cells were positive for CD73, CD90, CD105, CD44, CD29 and HLA-I, and negative for CD34 and HLA-class II, with a subpopulation that was negative for both HLA-I and HLA-II. Results from FISH demonstrated that 95–100% of UC-MSCs were of fetal origin. Telomere length of UC-MSCs was similar to that of Bone Marrow (BM) MSC from young donors (aged 20–30 years). At 5 days, the supernatant of UC-MSC cultures had immunosuppressive activity upon T-Lymphocyte cultures. The mixed UC-MSC population was able to differentiate towards osteogenic (monolayer), adipogenic, miogenic and chondrogenic (pellet culture). Chondrogenic differentiation on scaffolds was also confirmed; hypoxic condition improved the expression of chondrogenic markers. Osteogenic differentiation on scaffold was also confirmed after 20 days of culture. Discussion/Conclusions. These results suggest that the straightforward procedure of collecting UC-MCS at P1 from minced umbilical cord fragments can achieve a valuable cell population that seems to have a potential for orthopaedics tissue engineering such as the on-demand cell delivery using chondrogenic or osteogenic scaffold. The concept of this study may have a clinical relevance as a future hypothetical option for single-stage cartilage repair and bone regeneration

Objectives

Ligaments which heal spontaneously have a healing process that is similar to skin wound healing. Menopause impairs skin wound healing and may likewise impair ligament healing. Our purpose in this study was to investigate the effect of surgical menopause on ligament healing in a rabbit medial collateral ligament model.

We have undertaken a prospective study in patients with a fracture of the femoral shaft requiring intramedullary nailing to test the hypothesis that the femoral canal could be a potential source of the second hit phenomenon. We determined the local femoral intramedullary and peripheral release of interleukin-6 (IL-6) after fracture and subsequent intramedullary reaming.

In all patients, the fracture caused a significant increase in the local femoral concentrations of IL-6 compared to a femoral control group. The concentration of IL-6 in the local femoral environment was significantly higher than in the patients own matched blood samples from their peripheral circulation. The magnitude of the local femoral release of IL-6 after femoral fracture was independent of the injury severity score and whether the fracture was closed or open.

In patients who underwent intramedullary reaming of the femoral canal a further significant local release of IL-6 was demonstrated, providing evidence that intramedullary reaming can cause a significant local inflammatory reaction.

Our aim was to investigate the relationship between urinary excretion of deoxypyridinoline (DPD) as a marker of bone resorption, and Perthes’ disease. There were 39 children with Perthes’ disease in the florid stage who collected first-morning urine samples at regular intervals of at least three months. The level of urinary DPD was analysed by chemiluminescence immunoassay and was correlated with the radiological stage of the disease as classified by Waldenström, and the severity of epiphyseal involvement according to the classification systems of Catterall and Herring. The urinary DPD levels of a group of 44 healthy children were used as a control.

The median urinary DPD/creatinine (CREA) ratio was significantly reduced (p < 0.0001) in the condensation stage and increased to slightly elevated values at the final stage (p = 0.05) when compared with that of the control group. Herring-C patients showed significantly lower median DPD/CREA ratios than Herring-B patients (p = 0.03). The significantly decreased median DPD/CREA ratio in early Perthes’ disease indicated a reduced bone turnover and supports the theory of a systemic aetiology. Urinary levels of DPD may therefore be used to monitor the course of Perthes’ disease.