Physical activity and osseointegration: "step forward" to improve the quality of life of a trans-femoral amputee person

Lower limb amputation is an event that inevitably changes the lifestyle of the person with a significant impact on quality of life. The socket-type prosthesis entails that the residual limb is in direct contact with the socket which often implies numerous disadvantages. Osseointegrated prosthesis is a solution that avoids skin problems because not include the presence of the socket. In this type of prosthesis, a stem is surgically inserted inside the medullary canal and connected with the external prosthetic limb. Therefore, this thesis aims to highlight and explore the main strengths and problems of osseointegrated prostheses and to examine the role of physical activity, with attention to functional capacity and bone quality. The objectives of the thesis will be developed through 5 studies: (I) A gait analysis of a 44 years-old male patient who underwent surgery for the implantation of an osseointegrated prosthesis; (II) A systematic review to investigate the state of stump bone quality in patients with limb amputations; (III) A systematic review of the technologies involved in such devices has been carried out to identify the most fruitful ones in improving bone quality; (IV) A systematic review investigating the topic of physical activity and bone turnover biomarkers; (V) A systematic review to investigate the effects of physical activity interventions combined with drug treatments on bone biomarkers in people with osteopenia and osteoporosis. The integrated prosthesis is a good solution for people with lower limb amputation who cannot use their traditional socket-type prosthesis. Although many objectives have already been achieved, there are still many aspects that we can improve. These include the creation of a multidisciplinary path that support patients along their path, with particular attention to the pre-surgery and the post-rehabilitation phase that is still lacking even if of fundamental impact in determining the quality of life.

Development of newly conceived biomimetic nano-structured biomaterials as scaffolds for bone and osteochondral regeneration

The present research thesis was focused on the development of new biomaterials and devices for application in regenerative medicine, particularly in the repair/regeneration of bone and osteochondral regions affected by degenerative diseases such as Osteoarthritis and Osteoporosis or serious traumas. More specifically, the work was focused on the synthesis and physico-chemical-morphological characterization of: i) a new superparamagnetic apatite phase; ii) new biomimetic superparamagnetic bone and osteochondral scaffolds; iii) new bioactive bone cements for regenerative vertebroplasty. The new bio-devices were designed to exhibit high biomimicry with hard human tissues and with functionality promoting faster tissue repair and improved texturing. In particular, recent trends in tissue regeneration indicate magnetism as a new tool to stimulate cells towards tissue formation and organization; in this perspective a new superparamagnetic apatite was synthesized by doping apatite lattice with di-and trivalent iron ions during synthesis. This finding was the pin to synthesize newly conceived superparamagnetic bone and osteochondral scaffolds by reproducing in laboratory the biological processes yielding the formation of new bone, i.e. the self-assembly/organization of collagen fibrils and heterogeneous nucleation of nanosized, ionically substituted apatite mimicking the mineral part of bone. The new scaffolds can be magnetically switched on/off and function as workstations guiding fast tissue regeneration by minimally invasive and more efficient approaches. Moreover, in the view of specific treatments for patients affected by osteoporosis or traumas involving vertebrae weakening or fracture, the present work was also dedicated to the development of new self-setting injectable pastes based on strontium-substituted calcium phosphates, able to harden in vivo and transform into strontium-substituted hydroxyapatite. The addition of strontium may provide an anti-osteoporotic effect, aiding to restore the physiologic bone turnover. The ceramic-based paste was also added with bio-polymers, able to be progressively resorbed thus creating additional porosity in the cement body that favour cell colonization and osseointegration.

Studio della superficie degli impianti dentali in titanio: La nanotecnologia nella valutazione delle nuove superfici implantari in rapporto all'osteointegrazione dei mascellari

Il presente lavoro parte dalla descrizione dei processi di rimodellamento osseo mascellare a seguito della perdita di elementi dentari e la successiva riabilitazione mediante impianto dentale osteointegrato. Approfondiremo proprio i complessi aspetti dell’osteointegrazione su superfici implantari in titanio sia a livello micro che macroscopico. Nel campo dell’implantologia, infatti, il titanio risulta essere il materiale maggiormente impiegato in virtù della sua eccellente biocompatibilità e resistenza. Successivamente prenderemo in analisi i trattamenti di superficie implantare ad oggi più diffusi, lavorati prevalentemente a livello microscopico e infine confronteremo una sistematica trattata tradizionalmente con una innovativa trattata superficialmente a livello nanometrico. Il confronto avverrà in vivo, paragonando i risultati ottenuti clinicamente e radiograficamente tra le 2 sistematiche implantari, utilizzate per ripristinare la funzione masticatoria nei pazienti arruolati.

Studio e ottimizzazione del processo di fabbricazione additiva (SLM) per applicazioni in ambito biomedicale: produzione di protesi e strutture reticolari

Il progetto di dottorato che verrà presentato in questa tesi è focalizzato sullo sviluppo di un metodo sperimentale per la produzione di protesi personalizzate utilizzando il processo di fabbricazione additiva di Selective Laser Melting (SLM). L’obiettivo è quello di definire una condizione di processo ottimizzata per applicazioni in ambito chirurgico che possa essere generalizzabile, ovvero che ne garantisca la riproducibilità al variare dell’anatomia del paziente e che rappresenti la base per estendere il metodo ad altre componenti protesiche. Il lavoro si è sviluppato lungo due linee principali, la cui convergenza ha permesso di realizzare prototipi di protesi complete utilizzando un solo processo: da una parte la produzione di componenti a massima densità per il raggiungimento di elevate resistenze meccaniche, buona resistenza ad usura e corrosione e controllo di tensioni residue e deformazione delle parti stampate. Dall’altra si sono studiate strutture reticolari a geometria e porosità controllata per favorire l’osteointegrazione della componente protesica post impianto. In questo studio sono stati messe a confronto le possibili combinazioni tra parametri di processo e sono state individuate le correlazioni con le proprietà finali dei componenti stampati. Partendo da queste relazioni si sono sviluppate le strategie tecnologiche per la progettazione e la produzione dei componenti. I test sperimentali svolti e i risultati ottenuti hanno dimostrato la fattibilità dell’utilizzo del processo SLM per la produzione di protesi personalizzate e sono stati fabbricati i primi prototipi funzionali. La fabbricazione di protesi personalizzate richiede, però, anche la progettazione e la produzione di strumentario chirurgico ad hoc. Per questo motivo, parallelamente allo studio della lega di Cromo Cobalto, sono stati eseguiti i test anche su campioni in INOX 316L. Anche in questo caso è stato possibile individuare una finestra operativa di processo che garantisse proprietà meccaniche comparabili, e in alcuni casi superiori, a quelle ottenute con processi convenzionali.

Evaluation of deambulation in a protected environment and in the public green in limb amputated subjects treated through a new osteointegration method

The limb amputation is one of the oldest surgical procedures performed and it still represents an event that drastically changes the life of an individual. Despite the technological progress, the difficulties related to the realization and daily use of the socket remain very common. Among the different technologies adopted in the prosthetic field, this project focused on the osseointegration technique. This technique consists in implanting a stem within the medullary canal of the amputated skeletal segment that extends outside the amputation stump with a prosthesis, later connected to the metal extension. The objective of this PhD project is to treat and to evaluate selected patients with osseointegrated prosthetic implants for the treatment of lower limb amputations. Patients are recruited at the Rizzoli Orthopaedic Institute and at the Prosthesis - INAIL center of Vigorso (Budrio) during outpatient visits, while the surgical procedure is performed by the same expert surgeon in the II Orthopaedic and Traumatology Clinic of the Rizzoli Orthopaedic Institute. The project is still ongoing, to date three patients had completed both procedures, but due to various personal problems, just one of them is included in the analysis. This patient increased his percentage of prosthesis use and the level of mobility with an overall improvement of quality of live after the procedure. The osseointegration technique represents a promising alternative method of treatment for amputees who are not satisfied with their socket prosthesis. In the coming years it will continue the collection of clinical, radiographic and kinematic data of subjects undergoing this procedure in order to perform a long-term monitoring of both clinical outcomes and quality of life.