Bone defects and fractures, caused by injury, trauma or tumour resection require hospital treatment and temporary loss of mobility, representing an important burden for societies and health systems worldwide. Autografts are the gold standard for promoting new bone formation, but these may provide insufficient material and lead to donor site morbidity and pain. We previously showed that Fibrinogen (Fg) scaffolds promote bone regeneration in vivo (1), and that modifying them with 10mM of Magnesium (Mg) ions modulates macrophage response Herein, we aim to functionalize FgMg scaffolds with DC-EV, to promote recruitment and osteogenic differentiation of MSC. Scaffolds were produced by freeze-drying (2). Ethical permission was sought for all studies. Primary human peripheral blood monocyte-derived DC were cultured, their secreted EV were isolated by differential (ultra)-centrifugation and characterised by transmission electron microscopy and nanoparticle tracking analysis (3). Bone marrow MSC were used to determine the impact of EV-functionalized scaffolds through migration assays and their osteogenic differentiation was assessed by Alizarin Red staining. Fg and FgMg scaffolds functionalized with EV were characterized. Fg and FgMg scaffolds functionalized with DC-secreted EV were more efficient at recruiting MSC than scaffolds alone. MSC cultured on FgMg scaffolds showed significantly increased calcium deposits, in comparison with those cultured on Fg scaffolds. Fg scaffold modification by Mg promotes MSC osteogenic differentiation, while their functionalization with DC-secreted EV acts to promote MSC recruitment. This renders the FgMg-EV functionalized scaffolds an attractive material to promote new bone formation.
We report the clinical features and treatment on a rare case of Candida albicans lumbar spondylodiscitis in a non-immunocompromised patient. Its indolent course leads to delayed suspicion and diagnosis. As soon as fungal infection is suspected investigations with MRI and biopsy should be performed followed by medical therapy. Retrospective data analysis. A 58-year-old male underwent surgery for adenocarcinoma of the ampula of Vater treatment. Subsequently, the patient had a prolonged intensive care unit stay due to major complications, during his stay he developed a septicemia with Candida albicans isolated in the blood work. He received antifungal therapy anidulofungin, later changed to fluconazole during 2 weeks. Repeated blood work were negative and no vegetations on echocardiogram were seen. He was discharged from the ICU to a surgery floor. During the surgical unit stay he presented with lower back pain radiating to the lower limbs. Findings on neurological examination were normal, radiographs of the lumbar spine revealed L5-S1 antero listhesis. He was treated with oral non-steroidal anti-inflammatory drugs and an lumbar MRI and orthopaedic consultation was agended. One month later, after minor trauma he developed myelopathic symptoms with weakness of both lower limbs and severe back pain. Plain radiograph showed anterolistesis worsening. Magnetic resonance imaging showed endplate erosion at L5/S1. There also was evidence of paraspinal collection with epidural compression of the dural sac. The patient was treated surgicaly with debridement and posterior instrumented fusion from L4 to S1. Disk and end-plate material collected confirmed Candidal infection. The patient recovered most of his neurological deficit immediately after surgery. He was subsequently treated during 2 weeks with liposomal amphotericin B, later changed to fluconazole 400mg per os per day. He maintained antifungal therapy during 15 months. He remains asymptomatic with no recurrence of infection clinically or radiologically after surgery. Fungal spondylodiscitis is rare. Sub-acute or chronic low back pain in either immunocompromised or non-immunocompromised patients cronically ill and malnourished (parental nutrition) there must be high index of suspicion for fungal infections. Therefore we recommend screening for Candida osteomyelistis in these cases. Without treatment, involvement of vertebral bodies can lead to compression fractures, deformity of the spine and neurological impairment.
