Background

Although described as a commensal bacterium with low pathogenicity, Cutibacterium acnes involvement has been reported in many clinical entities: infections associated with devices, such as shoulder prosthetic joint infections, osteosynthesis, breast implants or cerebrospinal fluid shunts. Various studies show that C. acnes grows as a biofilm, contributing to its persistence by allowing its escape from the action of the immune system and antibiotics.

Extensive annulus fibrosus (AF) radial tears lead to intervertebral disc (IVD) herniation. While unrepaired defects in the AF are associated with postoperative reherniation and high IVD degeneration prevalence, current surgical strategies are limited to symptomatic treatment of pain and disregard the structural integrity of the AF. For all these reasons, this study is focused on i) designing polycaprolactone (PCL) electrospun implants that mimic the multi-lamellar fibrous structure of the native tissue and ii) assessing their ability to properly close and repair an AF defect in a sheep in vivo model. Oriented PCL mats were produced by electrospinning with average fiber diameters of 1.3µm and a tensile modulus (55±1MPa) matching the one of a native human AF lamella (∼47MPa). In vitro experiments demonstrated a spontaneous colonization of PCL mats by human and ovine AF cells. In vivo study was carried out on 6 sheep in which 5 lumbar discs were exposed using a left retroperitoneal approach. Defects (2×5mm, 2mm depth) were created in the outer annulus, with randomized distribution of conditions including 10-layer oriented or non-oriented mats, untreated and healthy groups. X-ray and MRI examinations were performed every month until explantations at 1, 3 and 6 months, followed by immuno-histological analysis. Data showed no dislocation of the implants, cell infiltration between the PCL mats and within the mats, and a continuous type I collagen tissue formation between the implants and the surrounding AF tissue. These results highlight that multi-layer PCL electrospun mat is a promising biomaterial for AF repair.

Skeletal sequels of traumatisms, diseases or surgery often lead to bone defects that fail to self-repair. Although the gold standard for bone reconstruction remains the autologous bone graft (ABG), it however exhibits some drawbacks and bone substitutes developed to replace ABG are still far for having its bone regeneration capacity. Herein, we aim to assess a new injectable allogeneic bone substitute (AlloBS) for bone reconstruction. Decellularized and viro-inactivated human femoral heads were crushed then sifted to obtain cortico-spongious powders (CSP). CSP were then partly demineralized and heated, resulting in AlloBS composed of particles consisting in a mineralized core surrounded by demineralized bone matrix, engulfed in a collagen I gelatin. Calvarial defects (5mm in diameter, n=6/condition) in syngeneic Lewis1A rats were filled with CSP, AlloBS±TBM (total bone marrow), BCP (biphasic calcium phosphate)±TBM or left unfilled (control). After 7 weeks, the mineral volume/total volume (MV/TV) ratios were measured by µCT and Movat's pentachrome staining were performed on undemineralized frontal sections. The MV/TV ratios in defects filled with CSP, AlloBS or BCP were equivalent, whereas the MV/TV ratio was higher in AlloBS+TBM compared to CSP, AlloBS or BCP (p<0.01; Mann-Whitney). Histological analyses exhibited a collagen-rich matrix in all the defects, and osteoid at the surface of all implanted biomaterials. Our data indicates that AlloBS is a promising candidate for bone reconstruction, with ease of manipulation, injectability and substantial osteogenic capacity. Further experiments in larger animal models are under consideration to assess whether AlloBS may be a relevant clinical alternative to ABG.