Treatment of knee articular cartilage defects: surgical strategies, results and analysis of factors determining the clinical outcome

Articular cartilage lesions, with their inherent limited healing potential, are hard to treat and remain a challenging problem for orthopedic surgeons. Despite the development of several treatment strategies, the real potential of each procedure in terms of clinical benefit and effects on the joint degeneration processes is not clear. Aim of this PhD project was to evaluate the results, both in terms of clinical and imaging improvement, of new promising procedures developed to address the challenging cartilage pathology. Several studies have been followed in parallel and completed over the 3-year PhD, and are reported in detail in the following pages. In particular, the studies have been focused on the evaluation of the treatment indications of a scaffold based autologous chondrocyte implantation procedure, documenting its results for the classic indication of focal traumatic lesions, as well as its use for the treatment of more challenging patients, older, with degenerative lesions, or even as salvage procedure for more advanced stages of articular degeneration. The second field of study involved the analysis of the results obtained treating lesions of the articular surface with a new biomimetic osteochondral scaffold, which showed promise for the treatment of defects where the entire osteochondral unit is involved. Finally, a new minimally invasive procedure based on the use of growth factors derived from autologous platelets has been explored, showing results and underlining indicatios for the treatment of cartilage lesions and different stages of joint degeneration. These studies shed some light on the potential of the evaluated procedures, underlining good results as well as limits, they give some indications on the most appropriate candidates for their application, and document the current knowledge on cartilage treatment procedures suggesting the limitations that need to be addressed by future studies to improve the management of cartilage lesions.

Nanoscale surface properties and interaction with fundamental biomolecules of chlorite and phlogopite

The surface properties of minerals have important implications in geology, environment, industry and biotechnology and for certain aspects in the research on the origin of life. This research project aims to widen the knowledge on the nanoscale surface properties of chlorite and phlogopite by means of advanced methodologies, and also to investigate the interaction of fundamental biomolecules, such as nucleotides, RNA, DNA and amino acid glycine with the surface of the selected phyllosilicates. Multiple advanced and complex experimental approaches based on scanning probe microscopy and spatially resolved spectroscopy were used and in some cases specifically developed. The results demonstrate that chlorite exposes at the surface atomically flat terraces with 0.5 nm steps typically generated by the fragmentation of the octahedral sheet of the interlayer (brucitic-type). This fragmentation at the nanoscale generates a high anisotropy and inhomogeneity with surface type and isomorphous cationic substitutions determining variations of the effective surface potential difference, ranging between 50-100 mV and 400-500 mV, when measured in air, between the TOT surface and the interlayer brucitic sheet. The surface potential was ascribed to be the driving force of the observed high affinity of the surface with the fundamental biomolecules, like single molecules of nucleotides, DNA, RNA and amino acids. Phlogopite was also observed to present an extended atomically flat surface, featuring negative surface potential values of some hundreds of millivolts and no significant local variations. Phlogopite surface was sometimes observed to present curvature features that may be ascribed to local substitutions of the interlayer cations or the presence of a crystal lattice mismatch or structural defects, such as stacking faults or dislocation loops. Surface chemistry was found similar to the bulk. The study of the interaction with nucleotides and glycine revealed a lower affinity with respect to the brucite-like surface of chlorite.