IBI is the result of the professional history and personal attitudes of each of its Founders and Board Members. This following is a selection of the top papers, published by Giuseppe Perale, Gianni Pertici, Michele Müller and Lorenzo Leoni in their careers, ranging from regenerative medicine to physical chemistry, from material science to biomaterials processing and from biology to biochemistry.
Dr. Maurizio Martini, Dr. Anna Zazzetta (Macerata, Italy – Dubai, UAE)
Bone grafting has always been considered a challenge for dentists. Initially the diffusion of this procedure was conditioned by the need of invasive surgery, bone harvesting and the morbidity of the patient. Now its diffusion will be ever more necessary due to the spread of implantology. SmartBone allows dentists to reduce the patient’s morbidity, have an optimal osteointegration in order to achieve the best outcomes in implant surgery. In particular, the service “SmartBone on Demand” allows to obtain a custom-made graft to provide the exact required quantity of bone for the specific needs of the patient.
Delfo D’Alessandro, Giuseppe Perale, Mario Milazzo, Stefania Moscato, Cesare Stefanini, Gianni Pertici, Serena Danti
The ideal scaffold for bone regeneration is required to be highly porous, non-immunogenic, biostable until the new tissue formation, bioresorbable and osteoconductive. This study aimed at investigating the process of new bone formation in patients treated with granular SmartBone for sinus augmentation, providing an extensive histologic analysis. Five biopsies were collected at 4–9 months post SmartBone implantation and processed for histochemistry and immunohistochemistry. Histomorphometric analysis was performed. Bone-particle conductivity index (BPCi) was used to assess SmartBone osteoconductivity. At 4 months, SmartBone (12%) and new bone (43.9%) were both present and surrounded by vascularized connective tissue (37.2%). New bone was grown on SmartBone1 (BPCi = 0.22). At 6 months, SmartBone was almost completely resorbed (0.5%) and new bone was massively present (80.8%). At 7 and 9 months, new bone accounted for a large volume fraction (79.3% and 67.4%, respectively) and SmartBone1 was resorbed (0.5% and 0%, respectively). Well-oriented lamellae and bone scars, typical of mature bone, were observed. In all the biopsies, bone matrix biomolecules and active osteoblasts were visible. The absence of inflammatory cells confirmed SmartBone1 biocompatibility and nonimmunogenicity. These data indicate that SmartBone1 is osteoconductive, promotes fast bone regeneration, leading to mature bone formation in about 7 months.
E.C. Ekwueme, J.M. Patel, J.W. Freeman, S. Danti
The skeletal system provides structure, protection, and movement to the body through bones, cartilages, tendons, and ligaments. Many congenital, traumatic, and degenerative diseases may affect the function of skeletal tissues during the life span, leading to the necessity of very specific replacements and treatments. In the widespread and mechanically constraining scenario of skeletal pathologies, biodegradable polymers can play unique roles that should not only be confined to adjuvant bulk devices. Tissue engineering has recently renewed the attention towards this class of biomaterials, enchantingly exploiting their outstanding versatility to accomplish smart and biomimetic solutions to surgical and therapeutic needs. This chapter describes the most recent achievements in this field, focusing on tissue type- and subtype-specific replacements, while taking into account clinical applications and future trends.
Ilaria Zollino, Giorgio Carusi, Francesco Carinci, Giuseppe Perale
The present case reports the success rate after 8 months of follow-up in a sinus pneumatization case with maxillary sinus floor cortical bone loss due to 2.5 dental agenesis. Rehabilitation including the opportunity to insert a contextual implant during maxillary sinus lift surgery was planned, using SmartBone® Microchips heterologous bone inserted into the maxillary sinus. The newly developed bone substitute was designed starting from bovine bone derived mineral matrix, reinforced with bioresorbable aliphatic polymers and cell nutrients. SmartBone® Microchips showed a tight contact with the new bone and neither gaps nor fibrous tissues at the interface. No inflammation or foreign body reaction were observed, and these findings support the good biocompatibility of SmartBone® Microchips composite material. Moreover, new bone, thanks to its mechanical properties, consented to fix screw in combination with maxillary sinus floor elevation for a dental implant.
The newly developed bone substitute SmartBone® Microchips showed in a patient with jaw cortical pavement defect a tight contact with the new bone and neither gaps nor fibrous tissues at the interface. No inflammation or foreign body reaction were observed, and these findings support the good biocompatibility of SmartBone® Microchips composite material. Moreover, new bone, thanks to its mechanical properties, consented to fix one screw in combination with maxillary sinus floor elevation for the dental implant. All these statements showed the good suitability of SmartBone® Microchips for alveolar defect repair in sinus lift procedure
Grecchi F, Perale G, Candotto V, Busato A, Pascali M, Carinci F
The repair of complex craniofacial bone defects is challenging and a successful result depends on the defect size, the quality of the soft tissue covering the defect and the choice of reconstructive method. Autologous bone grafts are the gold standard for bone replacement. Tissue engineered constructs are temporary substitutes developed to treat damaged or lost tissue. Recent advances in materials science have provided an abundance of innovations, underlining the increasing importance of polymer in this field. The Galeazzi Orthopedical institute of Milan received a Serbian soldier who reported a deep wound, due to the explosion of a grenade, during former-Yugoslavia’s war. His left cheekbone was completely lost, together with the floor of the left eye. SmartBone® technology allowed the realization of custom-made grafts which perfectly fitted the bone defect thanks to mechanical strength, also at small thicknesses, and the ability to be shaped without powder formation or unpredicted fractures. Tissue engineering approaches to regeneration utilize 3-dimensional (3D) biomaterial matrices that interact favorably with cells. The potential benefits of using a tissue engineering approach include reduced donor site morbidity, shortened operative time, decreased technical difficulty of the repair, ability to closely mimic the in vivo microenvironment in an attempt to recapitulate normal craniofacial development: this 36-month case study allowed to prove that SmartBone® custom-made bone grafts are an effective solution, gathering such benefits and being available now for daily routine.
Pertici G , Carinci F , Carusi G , Epistatus D , Villa T , Crivelli F , Rossi F , Perale G
Bovine bone xenografts, made of hydroxyapatite (HA), were coated with poly(L-lactide-co-ε-caprolactone) (PLCL) and RGD-containing collagen fragments in order to increase mechanical properties, hydrophilicity, cell adhesion and osteogenicity. In vitro the scaffold microstructure was investigated with Environmental Scanning Electronic Microscopy (ESEM) analysis and micro tomography, while mechanical properties were investigated by means compression tests. In addition, cell attachment and growth within the three-dimensional scaffold inner structure were validated using human osteosarcoma cell lines (SAOS-2 and MG-63). Standard ISO in vivo biocompatibility studies were carried out on model animals, while bone regenerations in humans were performed to assess the efficacy of the product. All results from in vitro to in vivo investigations are here reported, underlining that this scaffold promotes bone regeneration and has good clinical outcome.
G Pertici, F Rossi, T Casalini, G Perale
This study discusses composite polymer-coated mineral grafts for bone regeneration.
Bone xenografts are coated with degradable synthetic [poly(L-lactide-co-e-caprolactone)] and natural (polysaccharides) polymers in order to increase their mechanical properties, on one side, and to improve cell adhesion, on the other, with the purpose of developing a novel composite material for bone tissue engineering. In vitro assays help examine the microstructure of the scaffold by Fourier transform infrared and environmental scanning electron microscopy analyses and the porosity of the material by micro-computed tomography. The good adhesion property of polymer coated on to the mineral scaffold is deeply analysed and proved. The in vitro polymer degradation, in terms of time evolution of polymer-coating thickness, was rationalised with a mathematical model. The purpose of such modelling activity is to provide a simple but powerful tool to understand the influence of design parameters on coating behaviour.
The fabricated bone graft exhibited regular microstructure similar to healthy iliac bones with an average of 27% open porosity and an adequately rigid structure, which ensures a better osteointegration once implanted.
This approach avoids the use of trialand-error methods and consents a better a priori material design.
Filippo Rossi, Marco Santoro, Giuseppe Perale
Although bone has a high potential to regenerate itself after damage and injury, the efficacious repair
of large bone defects resulting from resection, trauma or non-union fractures still requires the
implantation of bone grafts. Materials science, in conjunction with biotechnology, can satisfy these
needs by developing artificial bones, synthetic substitutes and organ implants. In particular, recent
advances in polymer science have provided several innovations, underlying the increasing importance
of macromolecules in this field. To address the increasing need for improved bone substitutes,
tissue engineering seeks to create synthetic, three-dimensional scaffolds made from polymeric materials,
incorporating stem cells and growth factors, to induce new bone tissue formation. Polymeric
materials have shown a great affinity for cell transplantation and differentiation and, moreover, their
structure can be tuned in order to maintain an adequate mechanical resistance and contemporarily
be fully bioresorbable. This review emphasizes recent progress in polymer science that allows relaible
polymeric scaffolds to be synthesized for stem cell growth in bone regeneration. Copyright © 2013
John Wiley & Sons, Ltd.
S. Bardelli, G. Minonzio, G. Aita, G. Pertici, V. Albertini, D. Vigetti, M. Gola, T. Moccetti, T. Tallone, G. Soldati
Skeletal tissue loss due to congenital defects, disease and injury is normally treated by autologous tissue grafting. However, this method is limited by the availability of the host tissue, harvesting difficulties, donar site morbidity and che clinician’s ability to manipulate delicate 3D shapes. Therefore, the generation of autologous bone grafts in vitro avoiding the harvesting of autologous tissue at a second anatomie location is che ultimate goal in bone tissue engineering.