Publications

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

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.

Novel composite 3d scaffold for bone tissue engineering Novel composite 3d scaffold for bone tissue engineering
Date:2009
Journal:22nd European Conference on Biomaterials ESB 2009 - 07-11th September, Lausanne (Switzerland)
Authors:

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

Abstract

INTRODUCTION
Scaffolds for bone tissue engineering (t.e.) should ensure both mechanical stability and adequate strength and show a completely interconnected porous network for cell migration and proliferation, while also providing specific signals for bone regeneration. These issues are very well know ever since early maxillo-facial surgery in the 80’s. Moreover, connective tissue adhesion should be promoted. Biopolymers, bioglass and bioceramics are often considered to satisfy these requirements at least in part. Here, Industrie Biomediche Insubri S/A developed and produced a new composite 3D scaffold thought for bone t.e., particularly for maxillo-facial surgery, using a novel concept based on biomaterial assembly, thus avoiding drawbacks of interfacial bonding.

MATERIALS AND METHODS
This novel matrix has a composite structure based on a bone graft specifically reinforced with biodegradable polymers and bioactive agents. The bone grafts allow to maintain the adequate 3D-structure and porosity, the biopolymers permit to achieve good mechanical properties while bioactive agents promote cell adhesion and proliferation. All used components are approved for human use and scaffolds are produced according to GMP standards at the Micro-Sphere S/A facility. Both process and product are proprietary.

Microstructure was evaluated by SEM imaging (Evo 50EP, Zeiss-Cambridge Instruments, Germany). Handling tests were performed by surgeons to assess applicability in oral surgery. Preliminary in vitro tests with bovine chondrocytes were performed to evaluate the ability to support and promote cells proliferation within the matrix.

RESULTS
This novel composite 3D scaffold resulted feasible for oral surgery, being both easy to shape and resistant to screws and fixation manoeuvres. Moreover, SEM imaging confirmed that its microscopic structure resembles that of human cortical bone. Cell proliferation, assessed by Alamar Blue™ test, and viability resulted both positive and fully comparable in terms of values referred to controls. Further confirmations came from morphological analysis performed via SEM imaging.

CONCLUSIONS
Data collected represent a positive proof of concept for the developed process and the application of this new type of matrix as scaffold for bone tissue regeneration. Morphological analysis of structure confirmed the presence of a well diffused cortical bone human-like porosity. Preliminary mechanical investigation showed easy shaping by common surgical instruments in order to replicate and thus replace bone defects. Furthermore, preliminary biological investigations showed scaffolds to be promising substrates for cell adhesion and growth.

Bioresorbable bioactive bone matrix: a new 3d scaffold for tissue engineering in reconstructive maxillo-facial surgery Bioresorbable bioactive bone matrix: a new 3d scaffold for tissue engineering in reconstructive maxillo-facial surgery
Date:2009
Journal:The 7th International Stem Cell School in Regenerative Medicine, 2-4 Nov., Prague (Czech Republic)
Authors:

G. Pertici, M. Müller, G. Perale

Abstract

Scaffolds for bone tissue engineering (t.e.) 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 for bone regeneration. These specifications have been identified as stringent needs ever since early maxillo-facial surgery in the 80’s. Furthermore, connective tissue adhesion should be promoted too. In this framework, biopolymers, bioglass and bioceramics are often considered to satisfy these requirements, at least in part. Our approach was focused in finding a composite solution, bearing cues from both mineral components and polymeric ones. Indeed, here we present the first results of a new composite 3D scaffold thought for bone t.e., particularly for maxillo-facial surgery, using a novel concept based on biomaterial assembly , thus avoiding drawbacks of interfacial bonding.

This novel scaffold has a composite structure based on a bovine derived bone matrix specifically reinforced with biodegradable polymers and bioactive agents. The bovine derived matrix allows to maintain an adequate 3D-structure and porosity, the biopolymers permit to achieve good mechanical properties while bioactive agents promote cell adhesion and proliferation. Scaffolds are produced according to GMP standards  applying components which are all approved for human use. Both process and product are proprietary.

Microstructure was evaluated by E/SEM imaging (Evo 50EP, Zeiss-Cambridge Instruments). Biomechanical behaviour was assessed by monoaxial compression tests (MTS 858 MiniBionix), performed at constant compression speed of 1mm/60sec, comparing maximum linear stress and Young’s module of the new scaffold with those of the pure bovine derived matrix. Handling tests were performed by surgeons to assess applicability in oral surgery. Citocompatibility and cell viability were assessed by means of in vitro tests, performed with bovine chondrocytes and MG63 line cells (human osteosarcoma), aiming at evaluating the ability to support and to promote cells proliferation within the matrix.

This novel composite 3D scaffold resulted not only feasible for oral surgery, being both easy to shape and resistant to screws and fixation manoeuvres, but also better performing then nowadays available pure bovine derived matrix. Mechanical data indeed show that the polymeric reinforcement process improves by a factor 3 the maximum stress and the Young’s module, both being evaluated along the linear field. Specifically, the scaffold compression behaviour is that typical of an open cellular structure where a first pseudo-linear and pseudo-elastic behaviour, due to structural resistance, is then followed by oscillating behaviour due to progressive breakage of structure and consequent compacting of matrix. Stress, thus, appears to remain high but this effect is just due to pure compacting resistance, as structural integrity is definitely lost after the linear tract. Moreover, SEM imaging confirmed that its microscopic structure resembles that of human cortical bone: i.e. an open porous cellular matrix. Cell proliferation, assessed by Alamar Blue™ test, and viability resulted both positive and fully comparable in terms of values referred to controls. Further confirmations came from morphological analysis performed via SEM imaging.

Data collected represent a positive proof of concept for the developed process and the application of this new type of matrix as scaffold for bone tissue regeneration. Morphological analysis of structure confirmed the presence of a well diffused cortical bone human-like porosity. Preliminary mechanical investigation showed easy shaping by common surgical instruments in order to replicate and thus replace bone defects and a relevant improved resistance to compression with respect to nowadays available solutions. Furthermore, biological investigations showed scaffolds to be promising substrates for cell adhesion and growth, being strongly biocompatible and enhancing cell viability.

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