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R. Ferracini, A. Bistolfi, C. Guidotti, S. Artiaco, A. Battista, B. Battiston and G. Perale
Abstract: (1) Background: Recently, surgical treatment of distal radius fractures has increased
exponentially. Many locking plates’ fixation systems have been developed allowing a more stable
reduction and early mobilization. Sometimes, open reduction and fixation of distal radius fractures
may leave a residual bone loss requiring grafting. This retrospective study reports clinical and
radiologic outcomes of distal radius fractures treated with xenohybrid bone grafting in order to
assess (i) the safety of the investigated bone graft; (ii) its radiological integration and biomechanical
performances, and (iii) clinical outcomes of the patients; (2) Methods: We performed a retrospective
study on a cohort of 19 patients. Preoperative X-ray and CT scan were performed. The mean
clinical and radiographical follow-up was two years. Safety of the xenohybrid bone graft was
constantly evaluated. Clinical results were assessed through the DASH score and Mayo wrist score;
(3) Results: No adverse reactions, infections, and local or general complication were related to the use
of xenohybrid bone graft. The radiolucency of the xenografts suggested progressive osteointegration.
No evidence of bone graft resorption was detected. All the patients reached consolidation with good
to excellent clinical results; and (4) Conclusions: Clinical and radiological data demonstrated that
xenohybrid bone grafting promotes new bone formation and healing in osteopenic areas caused by
R. Ghiretti, C. F. Grottoli, A. Cingolani, G. Perale
Abstract: The case of a 59-year-old woman lacking bone in the lower left side of her mandible,
and treated with two different biomaterials for bone regeneration, is reported here. Specifically,
two different anatomical sites damaged by two different pathologies were studied: a radicular
fracture and peri-implantitis. The sites were treated via xenograft bone substitute and calcium
phosphosilicate, respectively. Follow-up evaluations showed that the two different methodologies
employing different materials in the same organism undergoing the same metabolic processes
achieved the same good results. This represents a significant change in current surgical strategies for
the dental region: instead of focusing on a single gold-standard technique, it is possible to follow a
hybrid approach by adapting the biomaterial and the protocol used to the specificities of the defect.
M. Boffano, N. Ratto, A. Conti , P. Pellegrino, L. Rossi, G. Perale and R. Piana
Several bone grafts are available for clinical use, each with their own peculiar biological
and mechanical properties. A new bone graft was obtained by combining mineral structures from
natural bovine bones with bioresorbable polymers and cellular nutrients. The study aims to evaluate
the clinical, biological and structural properties of this bone graft and its reliability in orthopedic
oncology. 23 adult patients (age range 18–85 years) were treated between October 2016 and December
2018; the oncologicdiagnoses were heterogeneous. After surgical curettage and bone grafting,
a clinical-radiological follow up was conducted. Radiographs were used to evaluate graft integration
according to the usual bone healing and oncologic follow up. Local complications (infection, local
recurrence, wound dehiscence, fracture or early reabsorption) were evaluated. The mean followup
was of 18.34 4.83 months. No fracture or infection occurred. One case of patellar Giant Cell
Tumor (GCT) and one of proximal tibia low-grade chondrosarcoma recurred after about one year.
Two wound dehiscences occurred (one required a local flap). Follow-up X-rays showed good to
excellent graft integration in most patients (20 out of 21). The investigated graft has a mechanical
and structural function that can allow early weight-bearing and avoid a preventive bone fixation
(only needed in four patients in this series). The graft blocks are dierent for shapes and dimensions,
but they can be customized by the producer or sawcut by the surgeon in the operating theatre to fit
the residual bone cavity. The complication rate was low, and a rapid integration was observed with
no inflammatory reaction in the surrounding tissues. Further studies are mandatory to confirm these
M. P. Cristalli, G. La Monaca, N. Pranno , S. Annibali , G. Iezzi, and I. Vozza
The present short communication described a new procedure for the reconstruction of the
horizontal severely resorbed edentulous maxilla with custom-made deproteinized bovine bone block,
fabricated using three-dimensional imaging of the patient and computer-aided design/computer-aided
manufacturing (CAD/CAM) technology. The protocol consisted of three phases. In the diagnosis and
treatment planning, cone-beam computed tomographic scans of the patient were saved in DICOM
(digital imaging and communication in medicine) format, anatomic and prosthetic data were imported
into a dedicated diagnostic and medical imaging software, the prosthetic-driven position of the
implants, and the graft blocks perfectly adapted to the residual bone structure were virtually planned.
In the manufacturing of customized graft blocks, the CAD-CAM technology and the bovine-derived
xenohybrid composite bone (SmartBone® on Demand – IBI SA – Industrie Biomediche Insubri SA
Switzerland) were used to fabricate the grafts in the exact shape of the 3D planning virtual model.
In the surgical and prosthetic procedure, the maxillary ridge augmentation with custom-made
blocks and implant-supported full-arch screw-retained rehabilitation were performed. The described
protocol oered some advantages when compared to conventional augmentation techniques. The use
of deproteinized bovine bone did not require additional surgery for bone harvesting, avoided the
risk of donor site morbidity, and provided unlimited biomaterial availability. The customization
of the graft blocks reduced the surgical invasiveness, shorting operating times because the manual
shaping of the blocks and its adaptation at recipient sites are not necessary and less dependent on the
clinician’s skill and experience.
M. Barbeck, O. Jung, X. Xiong, R. Krastev, T. Korzinskas, S. Najman, M. Radenkovi´c , N. Wegner , M. Knyazeva and
The present publication reports the purification effort of two natural bone blocks, that is, an
allogeneic bone block (maxgraft®, botiss biomaterials GmbH, Zossen, Germany) and a xenogeneic
block (SMARTBONE®, IBI S.A., Mezzovico-Vira, Switzerland) in addition to previously published
results based on histology. Furthermore, specialized scanning electron microscopy (SEM) and in vitro
analyses (XTT, BrdU, LDH) for testing of the cytocompatibility based on ISO 10993-5/-12 have been
conducted. The microscopic analyses showed that both bone blocks possess a trabecular structure
with a lamellar subarrangement. In the case of the xenogeneic bone block, only minor remnants of
collagenous structures were found, while in contrast high amounts of collagen were found associated
with the allogeneic bone matrix. Furthermore, only island-like remnants of the polymer coating
in case of the xenogeneic bone substitute seemed to be detectable. Finally, no remaining cells or
cellular remnants were found in both bone blocks. The in vitro analyses showed that both bone
blocks are biocompatible. Altogether, the purification level of both bone blocks seems to be favorable
for bone tissue regeneration without the risk for inflammatory responses or graft rejection. Moreover,
the analysis of the maxgraft® bone block showed that the underlying purification process allows
for preserving not only the calcified bone matrix but also high amounts of the intertrabecular
G.Perale , M. Monjo, J. M. Ramis, Ø. Øvrebø, F. Betge, P. Lyngstadaas and H. J. Haugen
Bone defects resulting from trauma, disease, surgery or congenital malformations are a
significant health problem worldwide. Consequently, bone is the second most transplanted tissue
just after blood. Although bone grafts (BGs) have been used for decades to improve bone repairs,
none of the currently available BGs possesses all the desirable characteristics. One way to overcome
such limitations is to introduce the feature of controlled release of active bone-promoting
biomolecules: however, the administration of, e.g., recombinant Bone morphogenetic proteins
(BMPs) have been used in concentrations overshooting physiologically occurring concentrations
and has thus raised concerns as documented side effects were recorded. Secondly, most such
biomolecules are very sensitive to organic solvents and this hinders their use. Here, we present a
novel xeno-hybrid bone graft, SmartBonePep®, with a new type of biomolecule (i.e., intrinsically
disordered proteins, IDPs) that is both resistant to processing with organic solvent and both triggers
bone cells proliferation and differentiation. SmartBonePep® is an advanced and improved
modification of SmartBone®, which is a bone substitute produced by combining naturally-derived
mineral bone structures with resorbable polymers and collagen fragments. Not only have we
demonstrated that Intrinsically Disordered Proteins (IDPs) can be successfully and safely loaded
onto a SmartBonePep®, withstanding the hefty manufacturing processes, but also made them
bioavailable in a tuneable manner and proved that these biomolecules are a robust and resilient
biomolecule family, being a better candidate with respect to other biomolecules for effectively
producing the next generation bone grafts. Most other biomolecules which enhances bone
formation, e.g., BMP, would not have tolerated the organic solvent used to produce SmartBonePep®.
Carlo Francesco Grottoli, Alberto Cingolani, Fabio Zambon , Riccardo Ferracini ,
Tomaso Villa and Giuseppe Perale
Abstract: Total hip arthroplasty (THA) is a surgical procedure for the replacement of hip joints with
artificial prostheses. Several approaches are currently employed in the treatment of this kind of defect.
Overall, the most common method involves using a quite invasive metallic support (a Burch–Schneider
ring). Moreover, valid alternatives and less invasive techniques still need to be supported by novel
material development. In this work, we evaluated the performance of SmartBone®, a xenohybrid
bone graft composed of a bovine bone matrix reinforced with biodegradable polymers and collagen,
as an eective support in acetabular prosthesis reconstruction. Specifically, the material’s mechanical
properties were experimentally determined (E = ~1.25 GPa, Ef = ~0.34 GPa, and Et = ~0.49 GPa) and
used for simulation of the hip joint system with a SmartBone® insert. Moreover, a comparison with a
similar case treated with a Burch–Schneider ring was also conducted. It was found that it is possible
to perform THA revision surgeries without the insertion of an invasive metal support and it can be
nicely combined with SmartBone®’s osteointegration characteristics. The material can withstand the
loads independently (max = ~12 MPa) or be supported by a thinner titanium plate in contact with
the bone in the worst cases. This way, improved bone regeneration can be achieved.
Riccardo Ferracini , Alessandro Bistolfi Riccardo Garibaldi , Vanessa Furfaro , Agnese Battista and Giuseppe Perale
Introduction: Tibial plateau fractures represent a common challenge for orthopaedic surgeons, sometimes representing complex cases to manage, where augmentation using bone grafts is required for stabilisation. Autologous iliac bone graft (AIBG) is the current gold standard for bone grafting. In order to overcome limitations related to the procedure, alternative strategies, like allogenic and xenogeneic bone substitutes have been investigated. Here, within the framework of an observational clinical study, we report clinical and radiological outcomes of patients treated for tibial plateau fractures with a composite xenohybrid bone graft, aiming at assessing clinical and radiological outcomes. Materials and Methods: We performed a cohort retrospective study of patients treated for tibial plateau fractures from May 2017 to January 2018. Thirty-four patients, i.e. 100% of those having received the bone graft under investigation for tibial plateaux fracture treatment, met the inclusion criteria and were enrolled in the study. Patients were assessed at 2 weeks, and then at a 1-, 3-, and 6-months, and 1-year follow-up. At each evaluation patients filled a visual analogue scale (VAS) for the level of pain during the day life activities and underwent physical exam and anteroposterior and lateral projection radiographs of the knee. At 1 year the Tegner Lysholm Scoring Scale, International Knee Document Committee 2000 (IKDC 2000), and Short Form (36) Health Survey (SF-36) were administered. Results: At 1-year, mean VAS decreased from 6.33 ± 1.40 to 1 ± 0.79 (P < 0.0001); Tegner Lysholm Scoring Scale was 89 ± 4.10 and mean IKDC 2000 was 78.67 ± 3.31. No infections, neurovascular complications or adverse effects related to implants were reported during the clinical exams at follow-up. Mean ROM was 124 ± 6°. Radiographs did not show defects of consolidation or progressive post-surgical subsidence and demonstrated a good grade of integration of the implant. Conclusions: Clinical and radiological outcomes, and scores of questionnaires, were good. The xenograft has demonstrated to be a safe biomaterial, with satisfactory mechanical and biological performances in the mid-term period. It also showed a high grade of osteointegration and remodelling
Enzo Facciuto, MD, Carlo Francesco Grottoli, MSE, Maurizio Mattarocci, MD, Fausto Illiano, MD, Mara Compagno, PhD, Riccardo Ferracini, MD, PhD, and Giuseppe Perale, MSE, PhD
This is a report of a 34-year-old male lacking of bone development in the frontal and orbital part of
the skull due to a surgical removal of a right orbital-front osteoma at the age of five. The integrity of the
craniofacial district was important for the young patient also for social acceptance and self-esteem.
Based on computed tomography patient images, a skull model was reconstructed, both digitally and on 3D real
model, to best design the needed bone graft. Defect wide extension and surface curvature called for the use of the
puzzle technique, where the whole graft is composed by several elements, mechanically slotting into each other. The
realization was made possible thanks to the use of a composite xenohybrid bone substitute specifically developed
for reconstructive surgery (SmartBone@, by Industrie Biomediche Insubri SA). SmartBone® technology allowed the
realization of custom-made grafts which perfectly joined each other and fitted the bone defect thanks to mechanical
strength, also at low thicknesses and wide extensions.
The postoperative course was uneventful and computed tomography scans showed new bone formation and
complete calvaria continuity already ten months after surgery, with no signs of inflammation over the entire follow
This case study represents a proof of concept that SmartBone® On Demand ™ custom-made bone grafts, together
with puzzle technique, are effective, easy to handle and provide final excellent functional and aesthetic results.
C. F. Grottoli, R. Ferracini, M. Compagno, A. Tombolesi, O. Rampado, L. Pilone, A. Bistolfi, A. Borrè, A. Cingolani
and G. Perale
(1) Background: Bone tissue engineering is a promising tool to develop new smart solutions
for regeneration of complex bone districts, from orthopedic to oral and maxillo-facial fields. In this
respect, a crucial characteristic for biomaterials is the ability to fully integrate within the patient
body. In this work, we developed a novel radiological approach, in substitution to invasive histology,
for evaluating the level of osteointegration and osteogenesis, in both qualitative and quantitative
manners. (2) SmartBone®, a composite xeno-hybrid bone graft, was selected as the base material
because of its remarkable effectiveness in clinical practice. Using pre- and post-surgery computed
tomography (CT), we built 3D models that faithfully represented the patient’s anatomy, with special
attention to the bone defects. (3) Results: This way, it was possible to assess whether the new
bone formation respected the natural geometry of the healthy bone. In all cases of the study (four
dental, one maxillo-facial, and one orthopedic) we evaluated the presence of new bone formation
and volumetric increase. (4) Conclusion: The newly established radiological protocol allowed the
tracking of SmartBone®effective integration and bone regeneration. Moreover, the patient’s anatomy
was completely restored in the defect area and functionality completely rehabilitated without foreign
body reaction or inflammation.
G. Perale, I. Roato, D.C. Belisario, M. Compagno, F. Mussano, T. Genova, F. Veneziano, G. Pertici, R. Ferracini
Intra-articular infusions of adipose tissue-derived stem cells (ASCs) are a promising tool for bone regenerative
medicine, thanks to their multilineage dierentiating ability. One major limitation of ASCs is represented by
the necessity to be isolated and expanded through in vitro culture, thus a strong interest was generated by the
adipose stromal vascular fraction (SVF), the non-cultured fraction of ASCs. Besides the easiness of retrieval,
handling and good availability, SVF is a heterogeneous population able to dierentiate in vitro into
osteoblasts, chondrocytes and adipocytes, according to the dierent stimuli received. We investigated and
compared the bone regenerative potential of SVF and ASCs, through their ability to grow on SmartBone®, a
composite xenohybrid bone scaold. SVF plated on SmartBone® showed better osteoinductive capabilities
than ASCs. Collagen I, osteocalcin and TGF markedly stained the new tissue on SmartBone®; microCT analysis
indicated a progressive increase in mineralised tissue apposition by quantication of newly formed trabeculae
(3391 ± 270,5 vs 1825 ± 133,4, p± 0,001); an increased secretion of soluble factors stimulating osteoblasts, as
VEGF (153,5 to 1278,1 pg/ml) and endothelin 1 (0,43 to 1,47 pg/ml), was detected over time. In conclusion, the
usage of SVF, whose handling doesn’t require manipulation in an in vitro culture, could denitively represent
a benet for a larger use in clinical applications. Our data strongly support an innovative idea for a bone
regenerative medicine based on resorbable scaold seeded with SVF, which will improve the precision of stem
cells implant and the quality of new bone formation.
Mohammed S. Abuelnaga, Nader N. Elbokle, Mohammed M. Khashaba
Aim: This study was to evaluate clinically and radiographically the volume changes of alveolar ridge grafting using
customized xenogenic bone graft.
Materials and Methods: A total of 12 patients with mandibular horizontal and vertical alveolar ridge defects ≥ 3 mm
were selected. They were divided into 2 groups: Group I (Test Group) included 6 patients in which mandibular alveolar
ridges were reconstructed with customized Xenogenic bone graft Smartbone (IBI S.A., Switzerland). Group II (Control
Group) included 6 patients in which mandibular alveolar ridges were reconstructed with particulate Xenogenic bone
(Smart bone, IBI S.A., Switzerland) grafting to posterior mandibular ridge with titanium mesh was performed. Volume
analysis of the changes in alveolar ridge in both Groups were obtained before and four months after the procedure using
CBCT. Densitometric analysis of the Postoperative bone formed and compared with native bone. .
Results: Four months postoperatively. Measurements made on cone-beam computerized tomograms, four months
postoperative showed significance increase in bone volume by 40 % in the area of newly formed bone in Group I
(Customized bone) compared with 23% in Control Group. Statistical significant changes was found in the density of
newly formed bone four months post-operatively in both Groups, however there was no significant difference in bone
density postoperatively between Group I (customized Bone) and Group II (Control).
Conclusion: According to the results, the treatment of defective alveolar ridge augmentation of the mandibular ridge with
customized xenogenic bone graft Smartbone (IBI S.A., Switzerland) is successful and produces results consistent with
the control Group.
A. Cingolani, C.F Grottoli, R. Esposito, T. Villa, F. Rossi, G. Perale
Background: The further functionalization of natural existing biomaterials is a very efficient method to introduce additional advanced characteristics on a unique structural composition and architecture.
Objective: As an example, different animal sources, if properly treated, can be used to develop bone xenograft active in hard tissues regeneration. In this sense, it is also important to consider that the selected process has to take into consideration the intrinsic variability of the base material itself and possibly being able to compensate for it.
Methods: In this work we characterize cancellous bovine bone treated by deposition of polymer and collagen and we show that the added components not only lead to a more resistant and more hydrophilic material, but also reduce the conventional correlation between apparent density and elastic modulus, which, in general, is a major source of uncertainty and risk in xenografts usage.
Results: Moreover, though intrinsically reinforcing the material, the deposition process leaves the specific open-porous structure, that allows cells proliferation and vessels ingrowth, basically unaltered.
Conclusion: The final material combines in a single piece and at the same time, mechanical resistance, homogeneous mechanical response and proper structural characteristics that allow further integration within the patient autochthonous tissues.
H. J. Haugen, S. P. Lyngstadaas, F. Rossi, G. Perale
Bovine xenograft materials, followed by synthetic biomaterials, which unfortunately still lack documented predictability and clinical performance, dominate the market for the cranio‐maxillofacial area. In Europe, new stringent regulations are expected to further limit the allograft market in the future
Within this narrative review, we discuss possible future biomaterials for bone replacement.
Although the bone graft (BG) literature is overflooded, only a handful of new BG substitutes are clinically available. Laboratory studies tend to focus on advanced production methods and novel biomaterial features, which can be costly to produce.
In this review, we ask why such a limited number of BGs are clinically available when compared to extensive laboratory studies. We also discuss what features are needed for an ideal BG.
We have identified the key properties of current bone substitutes and have provided important information to guide clinical decision‐making and generate new perspectives on bone substitutes. Our results indicated that different mechanical and biological properties are needed despite each having a broad spectrum of variations.
We foresee bone replacement composite materials with higher levels of bioactivity, providing an appropriate balance between bioabsorption and volume maintenance for achieving ideal bone remodelling.
F. Mandelli, G. Perale, S. Danti, D. D’Alessandro, P. Ghensi
Objectives.The aim of this case series study was to evaluate, clinically and histologically, the performances of a novel composite xenohybrid bone substitute.
Methods. Ten non-restorable teeth were extracted and socket preservation was performed with a bovine heterologous graft enriched with collagen and resorbable biopolymers (SmartBone®). The socket was covered with a collagen membrane firmly sutured. After five months of healing, implant site was prepared by means of a trephine bur and a dental implant was inserted. Specimens were sent for histological analysis. After three months of healing, patients received a provisional restoration followed by a definitive crown.
Results. All socket preservations healed uneventfully and, after five months, it was possible to insert implants with no additional bone augmentation procedures. All placed implants osseointegrated successfully and were in function after a minimum follow-up period of 30 months.
Conclusions. The tested biomaterial confirmed good clinical performance and, even if left exposed to the oral cavity covered with a collagen membrane, did not show signs of infection. Further research is desirable with a larger sample and variations of socket preservation technique to better understand the potential of this novel bone substitute.