Papers by Antonio Merolli
Studies in health technology and informatics, 1997

MRS Bulletin, 2000
Over the past decade, orthopedic surgery and related research have made increasing use of the opp... more Over the past decade, orthopedic surgery and related research have made increasing use of the opportunities offered by computers. Many clinical and research procedures rely on medical images (e.g., x-ray films and histology) and their numerical evaluation (e.g., geometric analysis and surface metrology). This has led to the development of computer applications in orthopedics, with computer graphics playing a fundamental role. The image-processing field has also been studied in greater depth, with a view toward enhancing systems automation.Image processing relies on capturing measurable variations in some image parameters (e.g., light intensity, color, and signal-to-noise ratio). The extracted numerical values then can be used to modify the source image. From this definition, image processing can be considered a measurement technique, and in this light it has been introduced into histomorpho-metrical practice.Image processing speeds up routine analysis procedures by evaluating, in a ...

Journal of Materials Science: Materials in Medicine
There has been an increased number of studies of nerve transection injuries with the sciatic nerv... more There has been an increased number of studies of nerve transection injuries with the sciatic nerve gap-injury model in the rabbit in the past 2 years. We wanted to define in greater detail what is needed to test artificial nerve guides in a sciatic nerve gap-injury model in the rabbit. We hope that this will help investigators to fully exploit the robust translational potential of the rabbit sciatic nerve gap-injury model in its capacity to test devices whose diameter and length are in the range of those commonly applied in hand and wrist surgery (diameter ranging between 2 and 4 mm; length up to 30 mm). We suggest that the rabbit model should replace the less translational rat model in nerve regeneration research. The rabbit sciatic model, however, requires an effective strategy to prevent and control self-mutilation of the foot in the postoperative period, and to prevent pressure ulcers.

Journal of Anatomy, 2021
Fluorescent markers, generally targeting neurotubules, are used to visualize the radiating crown ... more Fluorescent markers, generally targeting neurotubules, are used to visualize the radiating crown of growing neurites that is produced by dorsal root ganglion cells in vitro. Hoechst 33342 (2'‐[4‐ethoxyphenyl]‐5‐[4‐methyl‐1‐piperazinyl]‐2,5'‐bi‐1H‐benzimidazole trihydrochloride trihydrate) is a widely used fluorescent DNA marker that stain both live and fixed nuclei. We have recently found that H33342 can visualize the neurites of DRG too, but only when they are fixed in formalin. Images have a good signal‐to‐noise ratio. We noticed that besides H33342 being a specific marker for DNA, it also stains the transmembrane P‐glycoprotein (P‐gp) which is involved in the active pump‐out of alien molecules from the cytoplasm; so, H33342 remains associated with P‐gp after fixation. P‐gp is quite ubiquitous in healthy cells and, notably, P‐gp has been detected in DRG of several species as well as in human DRG. The use of H33342 as a staining for neurites of DRG in fixed samples could ha...

SARS-CoV-2 virions enter the host cells by docking their spike glycoproteins to the membrane-boun... more SARS-CoV-2 virions enter the host cells by docking their spike glycoproteins to the membrane-bound Angiotensin Converting Enzyme 2. After intracellular assembly, the newly formed virions are released from the infected cells to propagate the infection, using the extra-cytoplasmic ACE2 docking mechanism. However, the molecular events underpinning SARS-CoV-2 transmission between host cells are not fully understood. Here, we report the findings of a scanning Helium-ion microscopy study performed on Vero E6 cells infected with mNeonGreen-expressing SARS-CoV-2. Our data reveal, with unprecedented resolution, the presence of: 1)-long tunneling nanotubes that connect two or more host cells over submillimeter distances; 2)-large scale multiple cell fusion events (syncytia); and 3)-abundant extracellular vesicles of various sizes. Taken together, these ultrastructural features describe a novel intra-cytoplasmic connection among SARS-CoV-2 infected cells that may act as an alternative route of...

Journal of materials science. Materials in medicine, Jan 21, 2018
Osteoclasts are large multinucleated giant cells that actively resorb bone during the physiologic... more Osteoclasts are large multinucleated giant cells that actively resorb bone during the physiological bone turnover (BTO), which is the continuous cycle of bone resorption (by osteoclasts) followed by new bone formation (by osteoblasts). Osteoclasts secrete chemotactic signals to recruit cells for regeneration of vasculature and bone. We hypothesize that a biomaterial that attracts osteoclasts and re-establishes BTO will induce a better healing response than currently used bone graft materials. While the majority of bone regeneration efforts have focused on maximizing bone deposition, the novelty in this approach is the focus on stimulating osteoclastic resorption as the starter for BTO and its concurrent new vascularized bone formation. A biodegradable tyrosine-derived polycarbonate, E1001(1k), was chosen as the polymer base due to its ability to support bone regeneration in vivo. The polymer was functionalized with a RGD peptide or collagen I, or blended with β-tricalcium phosphate....

Journal of reconstructive microsurgery, Jan 6, 2018
We describe the development of a new surgical procedure to be used in the treatment of disruptiv... more We describe the development of a new surgical procedure to be used in the treatment of disruptive brachial plexus (BP) lesions. It is centered on an artificial device designed to assist nerve regeneration by providing a confined and protected environment. Nerve fibers can repair inside the device, while the adverse massive scar-tissue formation is limited to the outside of the device. Steps in the development of the procedure were (1) definition of the rationale, (2) design of the device, (3) choice of an in vivo translational model, (4)refinement of the surgical procedure, and (5) performance of an in vivo pilot study as a proof of concept. An interdisciplinary team from several laboratories was involved in this work over a period of 6 years. Results showed the absence of significant scar tissue in the regenerate and the presence of myelinated fibers aligned proximodistally between the stumps. This surgical approach can be seen not only as a definitive treatment but also as an e...

Journal of materials science. Materials in medicine, 2016
Application of carbon-fiber-reinforced-polymer (CFRP) artifacts in humans has been promoted in Or... more Application of carbon-fiber-reinforced-polymer (CFRP) artifacts in humans has been promoted in Orthopedic and Trauma Surgery. Literature documents the biocompatibility of materials used, namely carbon fibers (CF) and poly-ether thermoplastics, like poly-ether-ether-ketone (PEEK). A properly designed and accurately implanted composite artifact should not expose its fibers during or after surgery: however this may happen. A white Caucasian woman came to our attention 11 months after surgery for a wrist fracture. She had a severe impairment, being unable to flex the thumb; index finger and distal phalanx of third finger. We retrieved a correctly positioned plate and documented an aggressive erosive flexor tendons synovitis with eroded stumps of flexor tendons. The plate and soft tissues were analyzed by Visible Light and Scanning Electron Microscopy. Histopathology showed granulomatous fibrogenic process with CF engulfed inside multinucleated giant cells. Fibers were unmasked and disru...
Journal of Hand and Microsurgery, 2016
A complex digital injury, with tendon, nerve and bone losses, may pose the problem of which struc... more A complex digital injury, with tendon, nerve and bone losses, may pose the problem of which structure deserves the highest priority. Authors were able to treat tendon, nerve and bone lesions with the same level of priority thanks to the combined use of an external fixator and a nerve-guide.
Chirurgie de la Main, 2012
Journal of Materials Science: Materials in Medicine, 2006
The successful implantation of titanium-based implants for orthopaedic and dental applications is... more The successful implantation of titanium-based implants for orthopaedic and dental applications is often hindered because of their mobility, which arises because of a lack of direct binding of the metal surface to the mineral phase of the surrounding bone. Ceramic coatings, although ensuring the integration of the implant within the tissue, are unstable and carry risks of delamination and of failure. Recently, a novel biomimetic approach has been developed where porous titanium implants are coated with calcium-binding phospholipids able to catalyse the nucleation of discrete apatite crystals after only 30 min incubation in simulated body fluids.

Le guide neurali artificiali sono dei condotti cilindrici all'interno dei quali la rigenerazi... more Le guide neurali artificiali sono dei condotti cilindrici all'interno dei quali la rigenerazione nervosa può avvenire trovando una protezione dall'ambiente circostante ed un orientamento spazia-le. La loro introduzione nella pratica clinica risale a più di 20 anni fa, quando vennero proposte come alternativa all'innesto nervoso autologo (od autotrapianto) rispetto al quale evitano il sacrificio di un nervo sano da un sito donatore. Le prime guide furono proposte in silicone, quindi non degradabili in-vivo; pur mostrandosi in grado di favorire la rigenerazione nervosa, si rite sono state sviluppate guide in materiali degradabili in-vivo. L'analisi dei risultati clinici presentati nella letteratura interna-zionale mostra che le guide neurali possono portare a risultati comparabili a quelli ottenibili con gli innesti nervosi autologhi purché vengano utilizzate in perdite di sostanza inferiori ai 30 mm; in questi casi, esse presentano il significativo vantaggio di evitar...

Abstract: In the 1970s, morphological evidence collected by electron microscopy linked mineral de... more Abstract: In the 1970s, morphological evidence collected by electron microscopy linked mineral deposition ("calcification" or "mineralization") in newly-forming bone to membrane-encapsulated particles of a diameter of approximately 100 nm (50-200 nm) that were called "matrix vesiscles". As the characterisation of these vesicles progressed towards their biochemical composition, the role of lipids in the biomineralization process appeared to be crucial. In particular, a group of cell-membrane phospholipids were identified as major players in the crystal formation process. Indeed, in the 1980s it became clear that phosphatidylserine, together with proteins of the annexin family, was among the most important molecules in binding calcium ions and that this phospholipid was involved in the regulation of the early stages of mineralization in vivo. During the same period of time, the number of surgical implantations of orthopaedic, dental and maxilo-facial devi...

Journal of Neuroscience Methods
BACKGROUND Objective of our work was to develop a sequential double nonfluorescent immunostaining... more BACKGROUND Objective of our work was to develop a sequential double nonfluorescent immunostaining method which allows the selective identification of myelinated motor fibers in paraffin-embedded samples of peripheral nerves. Motor recovery after a nerve gap-lesion repaired by artificial nerve-guides ("conduits") is often less complete and slower than sensory recovery. The mechanism for this is not fully understood. NEW METHOD Incubation in sheep polyclonal choline acetyltransferase antibody (Abcam 18,736) at dilution of 1:150 was followed by incubation in mouse monoclonal anti-myelin basic protein antibody (Abcam 62,631) at a dilution of 1:5000. Counterstaining was performed with hematoxylin QS (Vector Labs H-3404). RESULTS Immunostaining of choline acetyltransferase and myelin basic protein can be combined together and results show a good contrast between the light brown of the choline acetyltransferase reaction product and the green of myelin basic protein reaction product. Cell nuclei are stained blue. This new protocol retains the advantages of paraffin embedded sections such as (i) having a relatively simple methodology, (ii) years-long storage life, and (iii) easy sharing among laboratories. Comparison with existing method. This specific combinatorial protocol has never been used before on paraffin embedded sections. It has been named "reciprocal nerve staining" (RNS). CONCLUSIONS Routine combination of choline acetyltransferase and myelin basic protein immunostaining provides a highly specific, highly contrasted paraffin-embedded sections where optical differentiation of myelinated motor fibers is easy and straightforward. This method will likely simplify and speed-up the routine histological study of nerve regeneration and will contribute a better identification of the nerve motor component.
An Introduction to Integrating Materials with Tissues, 2012
... 1976; Burr et al. 1985; Carter & Caler 1985; Odgaard & Weinans 1995; Burr 199... more ... 1976; Burr et al. 1985; Carter & Caler 1985; Odgaard & Weinans 1995; Burr 1997]. As anticipated in Section 3.3. 2, Wolff's law establishes that bone is deposited in proportion to the compression load that it must carry and that trabeculae follow the lines of stress. ...

Bone Repair Biomaterials, 2009
Different classes of materials have been used in orthopaedic surgery, which is one of the fields ... more Different classes of materials have been used in orthopaedic surgery, which is one of the fields in medicine where biomaterials have been most applied. In this chapter we will describe the different classes of materials and their applications in orthopaedic surgery, from the perspective of an orthopaedic surgeon. orthopaedic surgery deals with the treatment of pathological conditions of the musculoskeletal system. Its operative actions may be gathered into the following groups: (1) the geometrical correction of a deformed segment; (2) the replacement of joint components destroyed by a pathological process; (3) the restoration of the anatomical, and possibly mechanical, integrity of a bone defect. A wide range of operative techniques have been developed that can be be grouped in broad categories, the most important of which are osteosynthesis, joint replacement and bone replacement.

Orthopaedics & Traumatology-surgery & Research, 2011
Background: Trapeziectomy and ligament reconstructions are favoured by surgeons concerned that te... more Background: Trapeziectomy and ligament reconstructions are favoured by surgeons concerned that telescoping of the thumb may reduce its function. However, theoretically ligamentoplasties are at risk to develop tendinosis or tendon rupture or trigger a complex regional pain syndrome type 1. Hypothesis: Authors tested the looping of a slip from the abductor pollicis longus (APL) tendon around the first intermetacarpal ligament. They intended to use a surgical treatment which does not require bone tunnelling or looping around a tendon. Their results support the hypothesis that this new technique is a valid addition among treatments for carpometacarpal arthritis. Patients and methods: Forty-two patients were followed up to one year. Each patient had subjective assessment for: pain; function (DASH score); overall satisfaction. An objective assessment was used for: first web span angle; abduction and opposition; key pinch; grip strength. Tests were performed prior to surgery, then at three, six and 12 months. X-ray films were taken to monitor thumb height. Results: A substantial improvement in all these parameters was measured in all patients. Xray films showed the mantainance of a physiological heigth after one year. We recorded one complication of keloid and two of temporary dysesthesia but no case of tendinosis, delayed rupture, or CRPS 1. Mean operative time was 27 minutes. Discussion: Simplification and search for a technique which avoids the looping around a tendon is why the authors undertook this study. Advantages are the small number of required steps, short time of surgery and comfortable postoperative rehab regimen for the patient. The technique provides a distal anchoring point (without bone tunnelling). It is quite respectful
The use of general descriptive names, registered names, trademarks, etc. in this publication does... more The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature.
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Papers by Antonio Merolli