Matteo Santin

National Research Council, Roma, Latium, Italy

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Publications (92)182.76 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Calcium Phosphates are considered as biomaterials of choice for the treatment of critical size bone defects. Novel injectable calcium-phosphate materials integrating poly(-lysine) generation 3 dendrons tethered with phosphoserine were obtained by sol-gel synthesis. This type of dendron was integrated to mimic the biochemical structure of non-collagenous proteins present in the forming osteoids during bone repair. Sol-gel synthesis was coupled with a dialysis process able to equilibrate the materials at a physiological pH value. FTIR showed the successful retention of the dendrons after gel dialysis, while XRD analysis demonstrated both the pH-tuned formation of a hydroxyapatite crystalline phase within the gel and the complete removal of ammonium nitrate deriving from the sol-gel reaction solvent. SEM images confirmed the presence of crystalline domains in gels synthesised at pH 9.0. Injectability tests showed that the optimized formulations fulfilled the rheological properties required to minimally-invasive surgical procedures. Cytotoxicity tests on osteoblast-like MG-63 cells as well as morphology and viability studies showed that the dendrons induced a significantly higher levels of cell proliferation at early incubation time. Differentiation of the cell was also clearly enhanced at longer incubation time as demonstrated by both alkaline phosphatase activity and expression of typical markers. Altogether the data of this work indicate the clinical potential of the osteoid-mimicking calcium phosphate cements in minimally-invasive bone surgery.
    Tissue Engineering Part A 11/2013; · 4.64 Impact Factor
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    ABSTRACT: Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model. In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted. Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration. None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioning.
    European Spine Journal 10/2013; · 2.47 Impact Factor
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    ABSTRACT: Chronic and acute wounds can be quickly contaminated and infected by microorganisms such as bacteria, multi-resistant organisms or fungi. The introduction of silver as anti-microbial agent into wound management has widely been demonstrated to be effective and contribute to wound healing. As a consequence, many approaches and different materials have been employed to synthesize antibacterial silver-hydrogels. In this work the introduction of silver particles into the fibrillar structure of self-assembling aromatic di-phenylalanine derivatives modified with aromatic groups such as 9-fluorenylmethoxycarbonyl is proposed to produce antibacterial wound dressings. Hydrogels doped with increasing amounts of silver were tested and adopted to modify flax textiles. The influence of silver on the structure of hydrogels was studied using light and confocal microscopy, while SEM-EDX allowed the characterization of the hydrogel coating on the surface of the textile substrates as well as the identification and distribution of silver nanoparticles. The antibacterial potential of the treated flax was demonstrated through microbiological tests on Staphylococcus aureus. The combination of the physico-chemical and anti-bacterial properties, together with the ease of preparation of these biomaterials, fulfils the requirement of clinically-effective wound dressings.
    Journal of Materials Science Materials in Medicine 06/2013; · 2.14 Impact Factor
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    ABSTRACT: The lack of direct bonding between the surface of an implant and the mineralized bony tissue is among the main causes of aseptic loosening in titanium-based implants. Surface etching and ceramic coatings have led to improved osteointegration, but their clinical performance is still limited either by partial bonding or by coating delamination. In this work, a solid-phase synthesis method has been optimized to produce poly(ε-lysine) dendrons, the outermost branching generation of which is functionalized by phosphoserine (PS), a known catalyst of the biomineralization process. The dendrons were deposited onto etched titanium oxide surfaces as a near-to-monolayer film able to induce the formation of a homogeneous calcium phosphate phase in a simulated body fluid over 3 days. The dendron films also stimulated MG63 and SAOS-2 osteoblast-like cells to proliferate at a rate significantly higher than etched titanium, with SAOS-2 also showing a higher degree of differentiation over 14 days. PS-tethered dendron films were not affected by various sterilization methods and UV treatment appeared to improve the cell substrate potential of these films, thus suggesting their potential as a surface functionalization method for bone implants.
    Journal of The Royal Society Interface 02/2013; 10(79):20120765. · 4.91 Impact Factor
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    ABSTRACT: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to reduce pain and inflammation. However, their effect on bone metabolisms is not well known, and results in the literature are contradictory. The present study focusses on the effect of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid, at therapeutic doses, on different biochemical and phenotypic pathways in human osteoblast-like cells. Osteoblasts (MG-63 cell line) were incubated in culture medium with 1-10 μM of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid. Flow cytometry was used to study antigenic profile and phagocytic activity. The osteoblastic differentiation was evaluated by mineralization and synthesis of collagen fibers by microscopy and alkaline phosphatase activity (ALP) by spectrophotometric assay. Short-term treatment with therapeutic doses of NSAIDs modulated differentiation, antigenic profile, and phagocyte activity of osteoblast-like cells. The treatment reduced ALP synthesis and matrix mineralization. However, nonsignificant differences were observed on collagen syntheses after treatments. The percentage of CD54 expression was increased with all treatments. CD80, CD86, and HLA-DR showed a decreased expression, which depended on NSAID and the dose applied. The treatments also decreased phagocyte activity in this cellular population. The results of this paper provide evidences that NSAIDs inhibit the osteoblast differentiation process thus reducing their ability to produce new bone mineralized extracellular matrix.
    The Scientific World Journal 01/2013; 2013:809891. · 1.73 Impact Factor
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    ABSTRACT: OBJECTIVES: Phosphoserine-based functionalization has been proposed as a tool to improve integration of endosseous implants by promoting osteoblast adhesion and differentiation in vitro. The present work investigates whether phosphoserine-tethered poly(epsilon-lysine) dendrons, when applied as a film to titanium surfaces, enhance the differentiation of osteoblastic cells and the activation of Wnt/β-catenin signaling. MATERIALS AND METHODS: These films were tested in a murine model of calvaria-derived MC3T3 osteoblastic cells, primary bone marrow cells and mesenchymal, undifferentiated C2C12 cells. Gene expression was assayed by Real Time PCR, and activation of Wnt signaling pathway was measured with a reporter assay. RESULTS: Dendrons increased expression of alkaline phosphatase and osteocalcin, two osteoblastic markers, in both murine osteoblastic MC3T3 cells and primary bone marrow cells. The expression of osteoprotegerin, a protein opposing osteoclastogenesis was also significantly higher in cells growing on dendron-coated substrates both at 3 and 6 days of culture. Similarly, the mRNA levels of Wisp-2 and of β-catenin, two Wnt target genes, were also markedly increased in this group at day 6. The activation of this signaling pathway in cells growing on the dendron-coated surfaces was confirmed by use of a TCF/β-catenin reporter system in the C2C12 cell line. CONCLUSIONS: The findings of the present study show that phosphoserine-tethered poly(epsilon-lysine) dendron films act as stimuli for the activation of specific signal cascades and promote the differentiation of adhering progenitor cells into an osteoblastic phenotype.
    Clinical Oral Implants Research 12/2012; · 3.43 Impact Factor
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    ABSTRACT: Background: Among the different causes of orthopedic and dental implant failure, infection remains the most serious and devastating complication associated with biomaterial devices. Purpose: The aim of this study was to develop an innovative osteointegrative and antibacterial biomimetic coating on titanium and to perform a chemical-physical and in vitro biological characterization of the coating using the SAOS-2 cell line. We also studied the antibacterial properties of the coating against both Gram-positive and Gram-negative bacteria strains. Methods: An electrochemical solution containing silicon, calcium, phosphorous, sodium, and silver nanoparticles was used to obtain the antibacterial by Anodic Spark Deposition (ASD) treatment. Surface morphology was characterized using SEM and laser profilometry. A qualitative analysis of the chemical composition of the coating was assessed by EDS. The adhesion properties of the coating to the titanium bulk were performed with a 3-point bending test. SAOS-2 osteoblastic cell line spreading and morphology and viability were investigated. The bacterial adhesion and the antibacterial properties were investigated after 3 h and 24 h of incubation with Streptococcus mutans, Streptococcus epidermidis, and Escherichia coli bacterial strains. Results: The proposed anodization treatment created a chemically and morphologically modified, adherent titanium oxide layer, characterized by a microporous morphology enriched by calcium, silicon, phosphorous, and silver. The preliminary biological characterization showed optimal SAOS-2 cell adhesion and proliferation as well as a strong antibacterial effect. Conclusions: Based on the results of this study, we believe that this novel biomimetic and antibacterial treatment hold promise for enhancing osteointegration while conferring strong antibacterial properties to titanium.
    The International journal of artificial organs 10/2012; · 1.76 Impact Factor
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    ABSTRACT: The successful regeneration of large defects in traumatized and diseased tissues depends on the availability of biodegradable and bioactive biomaterials able to guide the tissue during its repair by offering both a physical support and a control of its biological mechanisms. Recently, a novel class of natural, biodegradable biomaterials has been obtained by the thermosetting of defatted soy curd. These biomaterials have been shown to regulate the activity of both tissue and inflammatory cells. Here, soybean-based hydrogels with different physicochemical properties and bioactivity have been obtained with a relatively simple and highly reproducible processing method. The content of the different soy components (e.g., the isoflavones) was tuned varying the solvent system during the extraction procedure, while variations in the material crosslinking provided either loose hydrogels or a bioglue. The biomaterials obtained can be used as either bioadhesives or injectable formulations in regenerative medicine as they were shown to stimulate the synthesis of collagen by fibroblasts and the formation of mineralized bone noduli by osteoblasts.
    Tissue Engineering Part A 05/2012; 18(17-18):1932-9. · 4.64 Impact Factor
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    ABSTRACT: In this study we chemospecifically functionalized alginate with thiol-ended peptides for tissue engineering (TE); a carbodiimide linker and the disulfide exchange scheme were used. First carboxyls of alginate were activated by introducing N-hydroxysuccinimide (NHS) ester groups; these react with primary amines of the heterobifunctional reagent 2-(2-pyridyldithio)ethyleneamine (PDEA). Thiol-reactive alginate (alginate-S-S-py) forms as cross-linking intermediate. The degree of pyridyldithio-functionalization is modified through variable PDEA concentration and it was determined using UV–VIS spectroscopy and proton nuclear magnetic resonance. The applicability of the alginate-S-S-py as platform for the chemoselective coupling of thiol-ended peptides was tested with glutathione as model peptide. Other SH-terminal peptides were successfully cross-linked. Moreover, the peptide–alginate keeps its gel-forming ability when treated with Ca2+ cations, leading to functionalized hydrogels that can be further used to obtain different multicomponent systems. The developed chemoselective strategy of functionalizing alginate with thiol-ended peptides could enhance the potential of this polymer for TE.
    Carbohydrate Polymers 05/2012; · 3.48 Impact Factor
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    ABSTRACT: The regeneration of cartilage in the intervertebral disc nucleus pulposus and joints is impaired by the formation of fibrocartilage that is caused by the invasion of the tissue by blood vessels. Peptides have been identified by phage display technique which are able to bind VEGF thus inhibiting angiogenesis. The present works focusses on the synthesis of poly(epsilon-lysine) dendrons of three branching generations in which the molecular root of the dendron bears a di-phenylalanine sequence to promote hydrophobic interactions with material surfaces and the uppermost molecular branches are functionalised with the amino acid sequenceWHLPFKC that is known to block VEGF. These biofunctionalised dendrons were entrapped in methacrylated Gellan Gum (GG-MA) hydrogels and tested for their ability to inhibit endothelial cell sprouting by both a 3D in vitro cell models and an in ovo model. The results show that when GG-MA is functionalised with the dendronised VEGF blockers, a regression of angiogenesis takes place around the hydrogel boundary. The in ovo study supports these findings as the GG-MA functionalised with the dendronised VEGF blockers did not elicit any acute inflammatory response, and decrease the number of converging macroscopic blood vessels as compared to positive controls. Moreover, the hydrogels prevented the infiltration of blood vessels, after 4 days of implantation.
    Journal of Tissue Engineering and Regenerative Medicine. 01/2012; 6(Suppl. 1):193-193.
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    ABSTRACT: To overcome the lack of in vivo stability of certain peptides used in cancer treatment and to increase their retention time in the extracellular matrix of the target tissue, the anti-angiogenic WHLPFKC sequence is synthesised at the uppermost branching generation of a poly(ε-lysine) dendron. The root of these dendrons is designed to interact preferentially with macromolecules of the extracellular matrix, whilst the uppermost branching generation of the dendron increased the exposed density of the bioactive peptide. Bioactivity testing of the blockers is performed on HUVECs. The results show that the dendron tethered with VEGF blockers was still able to inhibit proliferation and angiogenesis. Their relatively larger structure did not prevent the interaction with VEGF.
    Macromolecular Bioscience 11/2011; 11(12):1761-5. · 3.74 Impact Factor
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    ABSTRACT: Despite their known osteoconductivity, clinical use of calcium phosphate cements is limited both by their relatively slow rate of resorption and by rheological properties incompatible with injectability. Bone in-growth and material resorption have been improved by the development of porous calcium phosphate cements. However, injectable formulations have so far only been obtained through the addition of relatively toxic surfactants. The present work describes the response of osteoblasts to a novel injectable foamed bone cement based on a composite formulation including the bioactive foaming agents soybean and gelatine. The foaming properties of both defatted soybean and gelatine gels were exploited to develop a self-hardening soy/gelatine/hydroxyapatite composite foam able to retain porosity upon injection. After setting, the foamed paste produced a calcium-deficient hydroxyapatite scaffold, showing good injectability and cohesion as well as interconnected porosity after injection. The intrinsic bioactivity of soybean and gelatine was shown to favour osteoblast adhesion and growth. These findings suggest that injectable, porous and bioactive calcium phosphate cements can be produced for bone regeneration through minimally invasive surgery.
    Acta biomaterialia 12/2010; 7(4):1780-7. · 5.09 Impact Factor
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    ABSTRACT: In-stent restenosis is a clinical complication following coronary angioplasty caused by the implantation of the metal device in the atherosclerotic vessel. Histological examination has shown a clear contribution of both inflammatory and smooth muscle cells (SMCs) to the deposition of an excess of neointimal tissue. However, the sequence of events leading to clinically relevant restenosis is unknown. This paper aims to study the phenotype of SMCs when adhering on substrates and exposed to biochemical stimuli typical of the early phases of stent implantation. In particular, human SMC phenotype was studied when adhering on extracellular matrix-like material (collagen-rich gel), thrombus-like material (fibrin gel) and stent material (stainless steel) in the presence or absence of a platelet-derived growth factor (PDGF) stimulus. Cells on the collagen and fibrin-rich substrates maintained their contractile phenotype. By contrast, cells on stainless steel acquired a secretory phenotype with a proliferation rate 50 per cent higher than cells on the natural substrates. Cells on stainless steel also showed an increase in PDGF-BB receptor expression, thus explaining the increase in proliferation observed when cells were subject to PDGF-BB stimuli. The stainless steel substrate also promoted a different pattern of β1-integrin localization and an altered expression of hyaluronan (HA) synthase isoforms where the synthesis of high-molecular-weight HA seemed to be favoured. These findings highlighted the induction of a phenotypic pattern in SMC by the stainless steel substrate whereby the formation of a HA-rich neointimal tissue is enhanced.
    Journal of The Royal Society Interface 11/2010; 8(58):641-9. · 4.91 Impact Factor
  • Joe Lacey, A.Meroli, Matteo Santin
    Tissue Engineering and regenerative medicine (TERMIS); 06/2010
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    ABSTRACT: The 'gold standard' for bone filling is currently the bone autograft, but its use is limited by material availability and by the possible risks of infection or other donor site morbidity. Materials proposed so far as bone fillers do not show all the characteristics which are desirable. These are (a) osteoconductivity, (b) controlled biodegradation and (c) ease of adaptation to the implantation site. Recently, a new class of biodegradable material based on soybeans has been presented which shows good mechanical properties and an intrinsic bioactivity on inflammatory and tissue cells in vitro. The authors investigated the morphology in vivo of bone response in repairing a surgical lesion in the presence of granules of a novel soybean-based biomaterial (SB), comparing it with a sham-operated contralateral lesion of critical size (non-healing model); 26 operations were performed in New Zealand White rabbits, with back scattered electron microscopy as the analysis technique of choice. Implantation of SB granules over 8 weeks produced bone repair with features distinct from those obtained by healing in a non-treated defect. New and progressively maturing trabeculae appeared in the animal group where SB granules were implanted, while sham operation produced only a rim of pseudo-cortical bone still featuring a large defect. The trabeculae forming in the presence of SB granules had features typical of reticular bone. These findings suggest that the bone regeneration potential of SB granules and their intrinsic bioactivity, combined with their relatively easy and cost-effective preparation procedures, make them suitable candidates as a bone filler in clinical applications.
    Biomedical Materials 02/2010; 5(1):15008. · 2.17 Impact Factor
  • S. T. Meikle, G. Bianchi, M. Santin
    European Society for Biomaterials, 23rd European Conference on Biomaterials; 01/2010
  • European Society for Biomaterials, 23st European Conference on Biomaterials; 01/2010
  • British Pharmaceutical Conference, UK; 01/2010
  • UK Society for Biomaterials Conference; 01/2010
  • TERMIS; 01/2010

Publication Stats

726 Citations
182.76 Total Impact Points

Institutions

  • 2013
    • National Research Council
      • Institute for Composite and Biomedical Materials IMCB
      Roma, Latium, Italy
    • Università del Salento
      • Department of Engineering for Innovation
      Lecce, Apulia, Italy
  • 1997–2013
    • University of Brighton
      • School of Pharmacy and Biomolecular Sciences
      Brighton, ENG, United Kingdom
  • 2009
    • Istituto Ortopedico Rizzoli
      • Laboratory of Preclinical and Surgical Studies
      Bolonia, Emilia-Romagna, Italy
  • 2008
    • Brighton and Sussex Medical School
      Brighton, England, United Kingdom
  • 1999–2007
    • Amedeo Avogadro University of Eastern Piedmont
      Novara, Piedmont, Italy
  • 2006
    • Catholic University of the Sacred Heart
      Milano, Lombardy, Italy
  • 2005–2006
    • Politecnico di Milano
      • Department of Chemistry, Materials and Chemical Engineering "Giulio Natta"
      Milano, Lombardy, Italy
  • 1998
    • Università degli Studi di Torino
      • Dipartimento di Scienze Chirurgiche
      Torino, Piedmont, Italy