Publications

Follow the technical history of IBI products and keep yourself updated on new results.

Custom-made bone grafts for reconstructive maxillo-facial surgery: a case study Custom-made bone grafts for reconstructive maxillo-facial surgery: a case study
Date:2013
Journal:European Cells and Materials Vol. 26. Suppl. 2, 2013; Scandinavian society for biomaterials annual meeting Upsala
Authors:

G. Pertici, F. Grecchi, G. Perale

Abstract

Scaffolds for bone regeneration should ensure both mechanical stability and strength. Moreover, their intimate structure should have an adequate interconnected porous network for cell migration and proliferation, while also providing specific signals for bone regeneration. SmartBone® composite solution, based on a novel concept of biomaterial assembly, bearing cues from both mineral components and polymeric ones [1-3], was chosen to develop new patient-specific three-dimensional bone grafts. Indeed, thanks to mechanical performances and to full control over production, custom-made bone grafts can be produced according to the specific need of each single patient, via digital surgical planning, starting from CT scans.

http://www.ecmjournal.org

 

Polymeric scaffolds as stem cell carriers in bone repair Polymeric scaffolds as stem cell carriers in bone repair
Date:2013
Journal:Journal of Tissue Engineering and Regenerative Medicine (J Tissue Eng Regen Med)
Authors:

Filippo Rossi, Marco Santoro, Giuseppe Perale

Abstract

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.

SmartBone®: a new scaffold for regenerative medicine SmartBone®: a new scaffold for regenerative medicine
Date:2012
Journal:1st International Conference on Design and PROcesses for MEdical Devices - PROMED 2012 - 2-4 May, Padenghe sul Garda – Brescia (Italy)
Authors:

G. Pertici, M. Müller, F. Rossi, T. Villa, G. Carusi, S. Maccagnan, F. Carù, F. Crivelli, G. Perale

Abstract

Scaffolds for bone tissue engineering should ensure both mechanical stability and strength. Moreover, their intimate structure should have an adequate interconnected porous network for cell migration and proliferation, while also providing specific signals for bone regeneration.

A composite solution, based on a novel concept of biomaterial assembly, bearing cues from both mineral components and polymeric ones, was here followed to develop a new three-dimensional bone scaffold. A bovine derived mineral matrix was used to provide adequate 3D structure and porosity, while a resorbable biopolymer was used to reinforce it. Bioactive agents were added to promote cell adhesion and proliferation.

Microstructure was evaluated by E/SEM and micro-CT, confirming a strong resemblance with human cortical bone in terms of open mid-sized porosity. Compression tests evidenced a maximum stress capability (20MPa av.) three times higher than best available bovine derived bone, with a four-fold improved Young’s modulus (0.2GPa av.).

Overall mechanical behaviour was typical of open cellular structures: a first pseudo-linear and pseudo-elastic behaviour, due to structural resistance, was followed by oscillating behaviour due to progressive breakage of structure and consequent matrix compacting. Moreover, it resulted feasible for reconstructive surgery, being both easy to shape and resistant to screws and fixation manoeuvres.

Citocompatibility and cell viability were positively assessed in vitro with standard SAOS-2 and MG-63 line cells. Human adipose tissue derived mesenchymal stem cells were also tested and data showed in vitro capability to properly colonize the scaffold and, once induced, to differentiate.

Tibial grafts on adult white New Zealand rabbits were performed to assess in vivo osteointegration during 4 months observations. Histological analysis proved confirmation of matrix integration with natural bone and showed cells and vessels colonizing pores within it during time.

Data collected represent a complete proof of concept for this new scaffold and its application for bone tissue regeneration.

Microextrusion as a way for combining performance, functions and quality Microextrusion as a way for combining performance, functions and quality
Date:2012
Journal:1st International Conference on Design and PROcesses for MEdical Devices - PROMED 2012 - 2-4 May, Padenghe sul Garda – Brescia (Italy)
Authors:

S. Maccagnan, G. Perale, T. Cappelletti, G. Pertici

Abstract

Polymer processing is at the days of the more challenging evolutions of the medical device industry. The reason of that is strongly related to the molecular characteristics of the polymer, which are able to induce unique properties in the device and in each of its components. It is obvious that if the raw material gets spoiled during the process it will differ from the expected properties in a way that will be proportional to the level of complexity of the macromolecules.
Microexrtusion is a kind of process which allows not simply to preserve such properties, but also to combine several polymers with different properties in the same volume inducing different features on the base of the relative position within the device.

SmartBone® On Demand™: an innovative custom-made bone graft for reconstructive surgery SmartBone® On Demand™: an innovative custom-made bone graft for reconstructive surgery
Date:2012
Journal:1st International Conference on Design and PROcesses for MEdical Devices - PROMED 2012 - 2-4 May, Padenghe sul Garda – Brescia (Italy)
Authors:

G. Perale, G. Pertici, A. Motroni, L. Livi, A. Busato, F. Grecchi

Abstract

Industrie Biomediche Insubri SA (IBI) developed new technologies to improve the properties of natural materials for biomedical applications: indeed, IBI produces Smartbone®, a bone substitute specifically developed for orthopaedic reconstructive surgery. This innovative scaffold has a composite structure based on a bovine derived bone matrix reinforced with biodegradable polymers and bioactive agents.

The bovine derived matrix allows maintaining an adequate 3D-structure, with an open-porosity and a biomimetic chemistry (Ca and P based), biopolymers permit to achieve good mechanical properties (in the range of healthy human cortical bone), while bioactive agents promote cell adhesion, proliferation and high hydrophilicity (essential also for blood absorption and thus sparkling chemical signals cascade for regeneration). Smartbone® is produced according to GMP (Good Manufacturing Practice) standards, applying only human-use approved components and CE mark is under obtainment for both conventional and unconventional shapes.

Thanks to the very high performances of Smartbone®, particularly its impressively higher mechanical properties with respect to other bone substitutes, IBI developed and launched custom-made products, “SmartBone® on demand™”, solving single specific cases of bone reconstruction: starting from a common CT scan, IBI can provide the adequate substitute for every kind of defect.

This technology was successfully applied to a custom reconstruction of the left cheekbone portion of a young man who was hit by a grenade during former-Yugoslavian war. Patient CT scan was acquired, a 3D real model was built by stereolithography, grafts were manually shaped on the real model while planning surgery. Mathematical files of the so obtained grafts shapes were used to pilto a CAM 5-axis machine to cut the final shape of raw materials that were then reinforced with IBI’s proprietary process. Once in operatory room, present residuals, applied aside the battlefield, were removed, leaving space for the custom made graft. Surgery was fast and very precise allowing to obtain a very satisfactory result both in terms of anatomical reconstruction and also functional.

SMARTBONE: a new composite bone substitute for reconstructive surgery SMARTBONE: a new composite bone substitute for reconstructive surgery
Date:2012
Journal:Second 30 Bologna lnternational Symposium and Workshop
Authors:

G. Pertici, G. Carusi, G. Perale

Abstract

Nowadays the loss of bone due to congenital defects, diseases, injuries and trauma, is the most common cause of reconstructive orthopedic surgery; it accounts, just in the maxillo-facial district, hundreds of thousand cases each year worldwide. Furthermore, bone cancers and sarcomas (for example Ewing’s disease), even if very often prematurely diagnosed and treated, request relevant bone tissue excise and this kind of operations are criticai not only for aesthetical issues but especially for the residuai anatomica) functionality for the patients
Very often there is a need to fill/rebuild the defect or the eliminated district and, for self-evident reasons, the use of autologous bone is strongly not recommended; moreover if the site involved is quite large, it is very difficult to get the right amount of bone from the patient. Nevertheless, autologous bone graft still plays the role of gold standard in criticai sized and non-union bone defects, the main reason being the Jack of adequate industriai substitutes (synthetic and xenograft materials). Hence, today’s most commonly used solution today stil! remains the cadaveric bone graft, which is sometimes the only one available. Beside all known criticai issues of these grafts (e.g. ethical, availability and costs), the deep washing, deantigenation and sterilization processes make allograft materials very fragile bone substitutes, unable to withstand typical heavy surgical manoeuvres.
Industrie Biomediche Insubri SA (IBI) developed a new technology to improve the properties of natural materials. Indeed, IBI produces Smartbone®, a bone substitute specifically developed for orthopaedic reconstructive surgery. This innovative scaffold has a composite structure based on a bovine derived bone matrix reinforced with biodegradable polymers and bioactive agents. The bovine derived matrix allows maintaining an adequate 3D-structure, with an open-porosity and a biomimetic chemistry (Ca and P based), biopolymers pennit to achieve good mechanical properties (in the range of healthy human cortical bone), while bioactive agents promote cell adhesion, proliferation and high hydrophilicity ( essenti al also for blood absorption and thus sparkling chemical signals cascade for regeneration). Smartbonéì is produced according to GMP (Good Manufacturing Practice) standards, applying only human-use approved components and CE mark is under obtainment for both conventional and unconventional shapes.
Thanks to the very high performances of Smartbone”, particularly its irnpressively higher mechanical prope1ties with respect to other bone substitutes, !BI developed and launched custom­rnade products, ‘·SmartBone”‘ on demandTM”, solving single specific cases of bone reconstruction: stmting from a comrnon CT scan, !BI can provi de the adequate substitute for every kind of defect.

New regeneration technologies for bone and cartilage New regeneration technologies for bone and cartilage
Date:2011
Journal:ISPE
Authors:

G. Perale

Abstract

Autograft is still playing the role of gold standard in critical sized and non-union bone defects in oral, maxillofacial and orthopaedic surgeries: adequate bone substitutes for remodelling of native bone tissue are a goal yet to achieve. Such bone scaffolds should ensure mechanical stability and strength while their intimate structure should have an adequate interconnected porous network for cells and vessels proliferation. In this framework IBI S/A applied a typical engineering method, developing a bottom-up solution, based on a multi-scale approach: healthy human bone microstructure was understood and mimicked in order to obtain the same macroscopic properties. IBI technology, born from research, was then scaled-up to industrial production. Indeed, a composite solution, bearing cues from both mineral components and polymeric ones, was followed to develop a new three-dimensional bone scaffold, briefly: a bovine derived mineral matrix is reinforced with biodegradable polymers and bioactive agents through a specific nano-emulsion proprietary bath. The bovine derived matrix allows maintaining an adequate 3D-structure and porosity; biopolymers permit to achieve good mechanical properties while bioactive agents promote cell adhesion and proliferation. 

Microstructure, evaluated by E/SEM and micro-CT scans, confirmed a strong resemblance with human cortical bone in terms of open mid-sized porosity. Compression tests evidenced a maximum stress capability (20MPa av.) and a Young’s modulus (0.2GPa av.) comparable with human ones. Further mechanical investigations showed easy shaping by common surgical instruments and high resistance to screws and fixation manoeuvres, thus being feasible to replicate and replace various bone defects. Biological and histological investigations showed scaffolds to be promising substrates for cell adhesion and growth: biocompatibility and cell viability were positively assessed in vitro with standard line cells and on reference animal models. Human adipose tissue derived mesenchymal stem cells were also tested and data showed capability to properly colonize the scaffold and, once induced, to differentiate. Clinical studies are presently undergoing. Collected data confirm the applicability of this novel composite bone substitute. 

Caring at safety as much as at innovation, bone scaffolds were designed according to most strict and severe quality standards and nowadays they’re produced according to GMP standards, applying only human-use approved components. CE marking is under request as a Class III Medical Device. 

IBI S/A is now following the same research & development approach to address the growing need of cartilage substitutes. Micro porous fibres are now under investigation for being used to build flat elastic meshes resembling natural cartilage extracellular structure. 

Bioresorbable Bioactive Matrix For Bone Reconstruction Bioresorbable Bioactive Matrix For Bone Reconstruction
Date:2011
Journal:
Authors:

 G. Pertici, M. Müller, S. Maccagnan and G. Perale 

Abstract

Autograft is still playing the role of gold standard in critical sized and non-union bone defects. Hence, adequate bone substitutes for remodelling of native bone tissue are a goal to achieve: biopolymers, bioglasses and bioceramics are often considered to satisfy, at least in part, requirements for bone regeneration, but composite solutions are believed to represent the future, bearing cues from both mineral components and polymeric ones. 

Innovative Bone Scaffold For Reconstructive Oral Surgery Innovative Bone Scaffold For Reconstructive Oral Surgery
Date:2011
Journal:
Authors:

 G. Pertici, M. Müller, S. Maccagnan, F. Rossi & G. Perale 

Abstract

Autograft is still playing the role of gold standard in critical sized and non-union bone defects in oral and maxillofacial surgeries 1. Hence, adequate bone substitutes for remodelling of native bone tissue are a goal yet to achieve. Indeed, such bone scaffolds should ensure both mechanical stability and strength. Moreover, their intimate structure should have an adequate interconnected porous network for cell and proliferation, while also providing specific signals for bone regeneration.

Bioresorbable bioactive bone scaffold: A new scaffold for regenerative medicine Bioresorbable bioactive bone scaffold: A new scaffold for regenerative medicine
Date:2011
Journal:European Symposium on Biomaterials and Related Areas EuroBioMat 2011
Authors:

G. Pertici, M. Müller, F. Rossi, T. Villa, G. Carusi, S. Maccagnan, F. Carù, F. Crivelli, G. Perale

Abstract

Scaffolds for bone tissue engineering should ensure both mechanical stability and strength. Moreover, their intimate structure should have an adeguate interconnected porous network for cell migration and proliferation, while also providing specific signals for bone regeneration.
A composite solution, based on a nove) concept of biomaterial assembly, bearing cues from both minerai components and polymeric ones, was here followed to develop a new three-dimensional bone scaffold. A bovine derived mineral matrix was used to provide adeguate 3D structure and porosity, while a resorbable biopolymer was used to reinforce it. Bioactive agents were added to promote cell adhesion and proliferation. Microstructure was evaluated by E/SEM and micro-CT, confirming a strong resemblance with human cortical bone in terms of open mid-sized porosity. Compression tests evidenced a maximum stress capability (20MPa av.) three times higher than best available bovine derived bone, with a four-fold improved Young’s modulus (0.2GPa av.). Overall mechanical behaviour was typical of open cellular structures: a first pseudo-linear and pseudo-elastic behaviour, due to structural resistance, was followed by oscillating behaviour due to progressive breakage of structure and conseguent matrix compacting. Moreover, it resulted feasible for reconstructive surgery, being both easy to shape and resistant to screws and fixation manoeuvres. Citocompatibility and cell viability were positively assessed in vitro with standard SAOS-2 and MG-63 line cells. Human adipose tissue derived mesenchymal stem cells were also tested and data showed in vitro capability to properly colonize the scaffold and, once induced, to differentiate. Tibia! grafts on adult white New Zealand rabbits were performed to assess in vivo osteointegration during 4 months observations. Histological analysis proved confirmation of matrix integration with natural bone and showed cells and vessels colonizing pores within it during time. Data collected represent a complete proof of concept for this new scaffold and its application for bone tissue regeneration.

Bone regeneration technology
Date:2010
Journal:OrthoTec Europe
Authors:

Industrie Biomediche Insubri SA

Bioresorbable bioactive matrix for bone regeneration Bioresorbable bioactive matrix for bone regeneration
Date:2009
Journal:Tissue Engineering Part A, Vol. 16(8): A-10 & International Tissue Engineering Congress BONE-TEC 2009 8-10 October - Hannover (Germany)
Authors:

G. Pertici, M. Müller, G. Perale

Abstract

OBJECTIVE
Even if since early ‘900 researchers have been focusing their efforts on bone replacement, autograft is still playing the role of gold standard in critical sized and non-union bone defects in oral and orthopaedic surgery. Hence, adequate bone substitutes for remodelling of native bone tissue are a goal to achieve: biopolymers, bioglasses and bioceramics are often considered to satisfy, at least in part, requirements for bone regeneration, but composite solutions are believed to represent the future, bearing cues from both mineral components and polymeric ones.

MATERIALS AND METHODS
The new proprietary scaffold developed by Industrie Biomediche Insubri SA has a composite structure based on a bovine derived bone matrix reinforced with biodegradable polymers and bioactive agents. Bovine derived matrix allows to maintain an adequate 3D-structure and porosity, biopolymers permit to achieve good mechanical properties while bioactive agents promote cell adhesion and proliferation. Scaffolds are produced according to GMP standards applying only human-use approved components.

RESULTS AND CONCLUSIONS
Experimental data collected gave a positive confirmation of the applicability of this novel composite matrix as scaffold for bone tissue regeneration and of its production process developed therewith. Indeed, morphological microstructure analysis confirmed a well diffused cortical bone human-like porosity. Mechanical investigation showed easy shaping by common surgical instruments, in order to replicate and thus replace bone defects, and a relevantly improved resistance to compression with respect to available solutions. Biological and histological investigations showed scaffolds to be promising substrates for cell adhesion and growth, being strongly biocompatible and enhancing cell viability.

Stem cells, biomaterials and nanotechnologies in regenerative medicine Stem cells, biomaterials and nanotechnologies in regenerative medicine
Date:2009
Journal:JOINT CONFERENCE OF THE CZECH AND SLOVAK NEUROSCIENCE SOCIETIES
Authors:

G. Pertici, M. Muller, F. Crivelli, G. Perale.

Abstract

Scaffolds for bone tissue engineering should ensure both mechanical stability and adequate strength. Moreover, their intimate structure should have an interconnected porous network for cell migration and proliferation, while also providing specific signals tor bone regeneration and induction. A composite solution, based on a novel concept of biomaterial assembly and bearing cues from both minerai components and polymeric ones, was here followed to develop a new 3D bone scaffold. Bovine derived minerai matrix was used to previde adequate 3D-structure and porosity while resorbable biopolymer permit to achieve good mechanical properties and bioactive agents promote cell adhesion and proliferation. Microstructure was evaluated by E/SEM imaging confirming a very strong resemblance with human cortical bone. Monoaxial compression test evidenced a 28MPa (averaged) maximum stress capability, 3 times higher then best available pure bovine derived bone, and an overall behaviour typical of open cellular structures, where a first pseudo-linear and pseudo­elastic behaviour, due to structural resistance, is followed by oscillating behaviour due to progressive breakage of structure and consequent compacting of matrix. Moreover, this new scaffold resulted feasible tor reconstructive arai and maxillo-facial surgery, being both easy to shape and resistant to screws and fixation manoeuvres. From a biologica! point of view, citocompatibility and cell viability were very positively assessed in vitro with standard SAOS-2 line cells, bovine derived chondrocytes and finally human line MG63 cells, resulting in all cases fully comparable to controls. Histological analysis proved further confirmation of matrix structure resembling human bone and sections performed on matrixes seeded with the aforementioned cells showed cells colonizing pores within the inner volume of the matrix. Data collected represent a positive proof of concept tor the developed process and the application of this new type of matrix as scaffold tor bone tissue regeneration and reconstructive surgery.

Clinically optimized cell culture conditions in combination with a new 3D scaffold for human mesenchymal stem cell bone tissue engineering Clinically optimized cell culture conditions in combination with a new 3D scaffold for human mesenchymal stem cell bone tissue engineering
Date:2009
Journal:Regenerative medicine, 2009, vol. 4(6):70-71; World Conference on Regenerative Medicine, Leipzig (Germany)
Authors:

S. Bardelli, G. Minonzio, G. Aita, G. Pertici, V. Albertini, D. Vigetti, M. Gola, T. Moccetti, T. Tallone, G. Soldati

Abstract

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.

New defined cell culture conditions in combination with a new 3d-scaffold for mscs bone tissue engineering New defined cell culture conditions in combination with a new 3d-scaffold for mscs bone tissue engineering
Date:2009
Journal:22nd European Conference on Biomaterials ESB 2009 - 07-11th September, Lausanne (Switzerland)
Authors:

T. Tallone, G. Minonzio, G. Pertici, G. Aita, S. Bardelli, M. Gola, V. Albertini and G. Soldati.

Abstract

INTRODUCTION
Skeletal tissue loss due to congenital defects, disease, and injury is normally treated by autologous tissue grafting, a method limited by the availability of the host tissue, harvesting difficulties, donor site morbidity, and clinician’s ability to manipulate delicate 3D shapes.

The generation of autologous bone grafts in vitro, avoiding the harvesting of autologous tissue at a second anatomic location is the ultimate goal in bone tissue engineering. To achieve this, three major components have to be developed and optimized: I) Cell culturing in a defined medium, II) The osteoinductive cocktail, III) The scaffold.

We have developed a protocol for the extraction and culturing of adipose tissue-derived mesenchymal stem cells (AT-MSCs) which fulfils the strict European regulations concerning the Advanced Therapy Medicinal Products. AT-MSCs were grown inside a new 3D-scaffold developed by Industrie Biomediche Insubri (Switzerland). This matrix is a composite material based on bovine bone grafts, biodegradable polymers and bioactive agents. The bone grafts allow to maintain the adequate 3D-structure, the biopolymers permit to achieve good mechanical characteristics and bioactive agents promote cell adhesion and proliferation. The differentiation of the AT-MSCs into osteogenic cells was triggered by a serum-free induction medium without the use of growth factors.

MATERIALS AND METHODS
AT-MSCs were obtained from liposuction aspirates, cultured and expanded using protocols developed in our laboratory. After seeding the AT-MSCs into the scaffold, the cells were cultured for two weeks in presence of a defined osteogenic induction medium which was optimized in our laboratory. After fixation of the cells with standard techniques, the scaffolds were cut into slices and examined by ESEM imaging in order to evaluate the morphology, the spreading, and adhesion properties of the cells. The ability of the cells to properly differentiate was explored using standard immuno-histochemical techniques.

RESULTS
We show that our composite scaffold, in combination with our defined culture conditions, is very suitable for the growth and differentiation of AT-MSCs into osteogenic cells.

CONCLUSIONS
The bone tissue engineering strategy described here appears to be very promising for the development of protocols suitable for the treatment of bone loss or injury. Thus, it would be very interesting to test the performance of our in vitro generated autologous bone graft in a clinical human study.

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