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.

Percezione della direzione del proprio movimento: dalla registrazione dell'attività corticale al modello computazionale.

The main aim of this thesis is strongly interdisciplinary: it involves and presumes a knowledge on Neurophysiology, to understand the mechanisms that undergo the studied phenomena, a knowledge and experience on Electronics, necessary during the hardware experimental set-up to acquire neuronal data, on Informatics and programming to write the code necessary to control the behaviours of the subjects during experiments and the visual presentation of stimuli. At last, neuronal and statistical models should be well known to help in interpreting data. The project started with an accurate bibliographic research: until now the mechanism of perception of heading (or direction of motion) are still poorly known. The main interest is to understand how the integration of visual information relative to our motion with eye position information happens. To investigate the cortical response to visual stimuli in motion and the integration with eye position, we decided to study an animal model, using Optic Flow expansion and contraction as visual stimuli. In the first chapter of the thesis, the basic aims of the research project are presented, together with the reasons why it’s interesting and important to study perception of motion. Moreover, this chapter describes the methods my research group thought to be more adequate to contribute to scientific community and underlines my personal contribute to the project. The second chapter presents an overview on useful knowledge to follow the main part of the thesis: it starts with a brief introduction on central nervous system, on cortical functions, then it presents more deeply associations areas, which are the main target of our study. Furthermore, it tries to explain why studies on animal models are necessary to understand mechanism at a cellular level, that could not be addressed on any other way. In the second part of the chapter, basics on electrophysiology and cellular communication are presented, together with traditional neuronal data analysis methods. The third chapter is intended to be a helpful resource for future works in the laboratory: it presents the hardware used for experimental sessions, how to control animal behaviour during the experiments by means of C routines and a software, and how to present visual stimuli on a screen. The forth chapter is the main core of the research project and the thesis. In the methods, experimental paradigms, visual stimuli and data analysis are presented. In the results, cellular response of area PEc to visual stimuli in motion combined with different eye positions are shown. In brief, this study led to the identification of different cellular behaviour in relation to focus of expansion (the direction of motion given by the optic flow pattern) and eye position. The originality and importance of the results are pointed out in the conclusions: this is the first study aimed to investigate perception of motion in this particular cortical area. In the last paragraph, a neuronal network model is presented: the aim is simulating cellular pre-saccadic and post-saccadic response of neuron in area PEc, during eye movement tasks. The same data presented in chapter four, are further analysed in chapter fifth. The analysis started from the observation of the neuronal responses during 1s time period in which the visual stimulation was the same. It was clear that cells activities showed oscillations in time, that had been neglected by the previous analysis based on mean firing frequency. Results distinguished two cellular behaviour by their response characteristics: some neurons showed oscillations that changed depending on eye and optic flow position, while others kept the same oscillations characteristics independent of the stimulus. The last chapter discusses the results of the research project, comments the originality and interdisciplinary of the study and proposes some future developments.

La Pace Calda. La nascita del movimento antinucleare negli Stati Uniti e in Gran Bretagna, 1957-1963

The aim of this proposal is to offer an alternative perspective on the study of Cold War, since insufficient attention is usually paid to those organizations that mobilized against the development and proliferation of nuclear weapons. The antinuclear movement began to mobilize between the 1950s and the 1960s, when it finally gained the attention of public opinion, and helped to build a sort of global conscience about nuclear bombs. This was due to the activism of a significant part of the international scientific community, which offered powerful intellectual and political legitimization to the struggle, and to the combined actions of the scientific and organized protests. This antinuclear conscience is something we usually tend to consider as a fait accompli in contemporary world, but the question is to show its roots, and the way it influenced statesmen and political choices during the period of nuclear confrontation of the early Cold War. To understand what this conscience could be and how it should be defined, we have to look at the very meaning of the nuclear weapons that has deeply modified the sense of war. Nuclear weapons seemed to be able to destroy human beings everywhere with no realistic forms of control of the damages they could set off, and they represented the last resource in the wide range of means of mass destruction. Even if we tend to consider this idea fully rational and incontrovertible, it was not immediately born with the birth of nuclear weapons themselves. Or, better, not everyone in the world did immediately share it. Due to the particular climate of Cold War confrontation, deeply influenced by the persistence of realistic paradigms in international relations, British and U.S. governments looked at nuclear weapons simply as «a bullet». From the Trinity Test to the signature of the Limited Test Ban Treaty in 1963, many things happened that helped to shift this view upon nuclear weapons. First of all, more than ten years of scientific protests provided a more concerned knowledge about consequences of nuclear tests and about the use of nuclear weapons. Many scientists devoted their social activities to inform public opinion and policy-makers about the real significance of the power of the atom and the related danger for human beings. Secondly, some public figures, as physicists, philosophers, biologists, chemists, and so on, appealed directly to the human community to «leave the folly and face reality», publicly sponsoring the antinuclear conscience. Then, several organizations leaded by political, religious or radical individuals gave to this protests a formal structure. The Campaign for Nuclear Disarmament in Great Britain, as well as the National Committee for a Sane Nuclear Policy in the U.S., represented the voice of the masses against the attempts of governments to present nuclear arsenals as a fundamental part of the international equilibrium. Therefore, the antinuclear conscience could be defined as an opposite feeling to the development and the use of nuclear weapons, able to create a political issue oriented to the influence of military and foreign policies. Only taking into consideration the strength of this pressure, it seems possible to understand not only the beginning of nuclear negotiations, but also the reasons that permitted Cold War to remain cold.

Per un'indagine comparata della relazione voce-movimento nel performer

The present study investigates the principles that effect the relationship between voice and movement in performance. The topic stresses a contemporary tendency, which emerges from the work of numerous artits and looks into a research field that has not yet been well explored. The research arises from what I observed and experienced during my performance practical work and what I deepened after theorical studies: expression through movement and voice reflects constant principles. The first two chapters of the former study analyze the compared lines of the inquiry, from a theoretical point of view (interior and exterior voice-movement spatial patterns, and temporal patterns) and a practical point of view referring to body, action and relation. The third one is a survey on 'vocal gesture' as devised by Francesca della Monica, a topic that finds here the first academic investigation, built after nine years sudies with the artist on the oral sources of her teaching. The research is based on practical and theorical sources (especially philosophical studies of Giovanni Piana, Carlo Serra, Merleau-Ponty; performing studies of Grotowski, Laban, Dalcroze, Tomatis; ancient greek philosophy and literature; bodywork tecqniques as Kineseology, Body-mind centering, Alexander, Feldenkrais). The purpose of the study is to theorize, sistematyze and expose clear lines of compared investigation awakening the performer's interest on a central issue of his work and drawing the researcher's attention to make further focusing on the matter. Abstract (Italian) La ricerca va incontro a una tendenza che la contemporaneità pone in risalto con l'opera di numerosi artisti, investigando un campo ancora poco visitato a livello critico. Essa teorizza, sistematizza ed espone le costanti riscontrate nella relazione tra voce e movimento. L'indagine deriva dal presupposto, a me suggerito dalla pratica e dallo scambio con maestri e performer, e qui approfondito e restituito a livello teorico, che nella danza e nel canto, nell'espressione attraverso il movimento o attraverso la voce, si riflettono gli stessi principi. La tesi è articolata in tre capitoli: i primi due sviluppano le linee di indagine comparata, prima da un punto di vista filosofico e poi da un punto di vista pratico, il terzo porta alla luce il concetto di gesto-vocale come inteso da Francesca della Monica, di cui questo studio rappresenta il primo contributo scientifico, aprendo una ricerca nuova agli studi di settore. Il primo capitolo, 'Risonanze', sviluppa le premesse filosofiche della questione, introduce il corpo come veicolo di voce e movimento, affronta il tema del movimento della voce nello spazio interno del corpo e nello spazio di relazione. Legge poi il movimento in termini temporali, secondo i concetti di istante, ritmo, forma e flusso. Il secondo capitolo, 'Costanti', espone le costanti concrete della relazione voce-movimento in riferimento allo spazio interno del corpo, all'azione, allo spazio esterno di relazione. Il terzo capitolo, 'Confini', analizza il gesto vocale, come inteso da Francesca della Monica, concetto sintesi dell'intera ricerca poiché integra, nella sua essenza, il movimento fisico e vocale, restituendo e approfondendo lo spettro di riflessioni emerse nei primi due capitoli. Il gesto vocale, nella sua accezione espressiva, così come il lavoro di Francesca della Monica, è ancora estraneo agli studi di settore e trova in questo studio un primo contributo accademico. Le fonti sono quelle dell'insegnamento orale di Francesca della Monica, che ho seguito per nove anni, fino a desumerne una mia personale sistematizzazione, integrata con altri punti di vista critici. Analizzo i diversi livelli di profondità del gesto vocale scandendo il tema secondo la categoria della relazione: relazioni motorie, relazioni materiche, relazioni spaziali, temporali, compositive e sinestesiche. Le fonti della ricerca sono scaturite da due sorgenti, quella sul campo, e quella della teoria, confluite qui in un unico flusso. Le fonti 'in presa diretta' sono state avvalorate e confrontate con le fonti relative agli studi di settore (in particolare per la filosofia Giovanni Piana, Carlo Serra, Merleau-Ponty, per il teatro, il canto e la danza Grotowski, Laban, Dalcroze, Tomatis) e le bodywork techniques (Kinesiologia, Body-mind centering, metodo Alexander, metodo Feldenkrais). Ampio spazio viene dato alla grecità antica, che propone sull'espressione di voce e movimento un pensiero integrato carico di speculazioni che racchiudono in nuce i principi sviluppati. Lo studio tenta di offrire un livello di lettura idoneo a suscitare l'interesse del performer, e a valere come momento di indagine per lo studioso, che possa da queste basi operare approfondimenti sulle connessioni proposte. L'obiettivo è restituire la conoscenza, intuita in virtù della pratica, elaborata ed arricchita grazie alla teoria, su un nodo fondamentale per gli studi teatrali e recente oggetto di attenzione da parte di critici e artisti.

Trattamento delle lesioni osteocondrali di grado I e II mediante infiltrazione intra-articolare di fattori di crescita autologhi (plasma rich in platelets)

The use of Platelet-rich plasma (PRP), a platelet concentrate made of autogenous blood, is becoming use in the treatment of some orthopaedic diseases. The aim of this study is to assess the effect of PRP on articular cartilage defects in a rabbit model (10 subjects). Twenty osteochondral defects created in the femoropatellar groove, were in ten cases left untreated and in ten cases treated with autogenous PRP. PRP was obtained using a double centrifugation of the rabbit’s blood harvested before the operation. 30 days after the lesion was made in both knee, the left one in each rabbit was treated by a PRP injection, followed by other two injection at 45 and 60 days. Tissue specimens were assessed by macroscopic examination and histological evaluation, that showed a better healing of the lesions in the knee treated with PRP injections.

Valutazione sperimentale della rigenerazione cartilaginea articolare dopo stimolazione biofisica con campi elettromagnetici pulsati in associazione a trattamenti chirurgici

Diverse tecniche di ingegneria tessutale sono state sviluppate per promuovere la riparazione delle lesioni della cartilagine articolare. Nonostante i buoni risultati clinici a breve termine, il tessuto rigenerato fallisce nel tempo poiché non possiede le caratteristiche meccaniche e funzionali della cartilagine articolare nativa. La stimolazione con campi elettromagnetici pulsati (CEMP) rappresenta un approccio terapeutico innovativo. I CEMP aumentano l’attività anabolica dei condrociti con conseguente incremento della sintesi della matrice, e limitano l’effetto catabolico delle citochine pro-infiammatorie riducendo la degradazione della cartilagine nel microambiente articolare. I CEMP agiscono mediante l’up-regolazione dei recettori adenosinici A2A potenziando il loro affetto anti-infiammatorio. Lo scopo di questo studio è stato quello di valutare l’effetto della stimolazione con CEMP sulla guarigione di difetti osteocondrali in un modello sperimentale nel coniglio. Un difetto osteocondrale del diametro di 4mm è stato eseguito nel condilo femorale mediale di entrambe le ginocchia di 20 conigli. A destra la lesione è stata lasciata a guarigione spontanea mentre a sinistra e stata trattata mediante inserimento di scaffold collagenico o trapianto di cellule mesenchimali midollari sul medesimo scaffold precedentemente prelevate dalla cresta iliaca. In base al trattamento eseguito 10 animali sono stati stimolati con CEMP 4 ore/die per 40 giorni mentre altri 10 hanno ricevuto stimolatori placebo. Dopo il sacrificio a 40 giorni, sono state eseguite analisi istologiche mediante un punteggio di O’Driscoll modificato. Confrontando le lesioni lasciate a guarigione spontanea, la stimolazione con CEMP ha migliorato significativamente il punteggio (p=0.021). Lo stesso risultato si è osservato nel confronto tra lesioni trattate mediante trapianto di cellule mesenchimali midollari (p=0.032). Nessuna differenza è stata osservata tra animali stimolati e placebo quando la lesione è stata trattata con il solo scaffold (p=0.413). La stimolazione con CEMP è risultata efficace nel promuovere la guarigione di difetti osteocartilaginei in associazione a tecniche chirurgiche di ingegneria tessutale.