An In Vitro Study on the Application of Silver-Doped Platelet-Rich Plasma in the Prevention of Post-Implant-Associated Infections.

Implant therapy is a common treatment option in dentistry and orthopedics, but its application is often associated with an increased risk of microbial contamination of the implant surfaces that cause bone tissue impairment. This study aims to develop two silver-enriched platelet-rich plasma (PRP) multifunctional scaffolds active at the same time in preventing implant-associated infections and stimulating bone regeneration. Commercial silver lactate (L) and newly synthesized silver deoxycholate:ß-Cyclodextrin (B), were studied in vitro. Initially, the antimicrobial activity of the two silver soluble forms and the PRP enriched with the two silver forms has been studied on microbial planktonic cells. At the same time, the biocompatibility of silver-enriched PRPs has been assessed by an MTT test on human primary osteoblasts (hOBs). Afterwards, an investigation was conducted to evaluate the activity of selected concentrations and forms of silver-enriched PRPs in inhibiting microbial biofilm formation and stimulating hOB differentiation. PRP-L (0.3 µg/mm2) and PRP-B (0.2 µg/mm2) counteract Staphylococcus aureus, Staphylococcus epidermidis and Candida albicans planktonic cell growth and biofilm formation, preserving hOB viability without interfering with their differentiation capability. Overall, the results obtained suggest that L- and B-enriched PRPs represent a promising preventive strategy against biofilm-related implant infections and demonstrate a new silver formulation that, together with increasing fibrin binding protecting silver in truncated cone-shaped cyclic oligosaccharides, achieved comparable inhibitory results on prokaryotic cells at a lower concentration.

Rhamnolipid 89 Biosurfactant Is Effective against Streptococcus oralis Biofilm and Preserves Osteoblast Behavior: Perspectives in Dental Implantology.

Biofilm-related peri-implant diseases represent the major complication for osteointegrated dental implants, requiring complex treatments or implant removal. Microbial biosurfactants emerged as new antibiofilm coating agents for implantable devices thanks to their high biocompatibility. This study aimed to assess the efficacy of the rhamnolipid 89 biosurfactant (R89BS) in limiting Streptococcus oralis biofilm formation and dislodging sessile cells from medical grade titanium, but preserving adhesion and proliferation of human osteoblasts. The inhibitory activity of a R89BS coating on S. oralis biofilm formation was assayed by quantifying biofilm biomass and microbial cells on titanium discs incubated up to 72 h. R89BS dispersal activity was addressed by measuring residual biomass of pre-formed biofilms after rhamnolipid treatment up to 24 h. Adhesion and proliferation of human primary osteoblasts on R89BS-coated titanium were evaluated by cell count and adenosine-triphosphate quantification, while cell differentiation was studied by measuring alkaline phosphatase activity and observing mineral deposition. Results showed that R89BS coating inhibited S. oralis biofilm formation by 80% at 72 h and dislodged 63-86% of pre-formed biofilms in 24 h according to concentration. No change in the adhesion of human osteoblasts was observed, whereas proliferation was reduced accompanied by an increase in cell differentiation. R89BS effectively counteracts S. oralis biofilm formation on titanium and preserves overall osteoblasts behavior representing a promising preventive strategy against biofilm-related peri-implant diseases.

The Number of Platelets in Patient's Blood Influences the Mechanical and Morphological Properties of PRP-Clot and Lysophosphatidic Acid Quantity in PRP.

The objectives of this study were to compare platelet-rich plasma (PRP) from patients with different concentrations of platelets and to assess the influence of these PRP preparations on human osteoblast (hOB) activity. In the literature, growth factors released by activated platelets have been considered responsible for the active role of PRP on bone regeneration but no specific role has been attributed to lysophosphatidic acid (LPA) as a possible effector of biological responses. In this study, patients were grouped into either group A (poor in platelets) or group B (rich in platelets). Clots from PRP fraction 2 (F2-clots), obtained with CaCl2 activation of PRP from the two groups, were compared macroscopically and microscopically and for their mechanical properties before testing their activity on the proliferation and migration of hOB. LPA was quantified before and after PRP fractioning and activation. The fibrin network of F2-clots from patients with a lower platelet concentration had an organized structure with large and distinct fibers while F2-clots from patients in group B revealed a similar structure to those in group A but with a slight increase in density. ELISA results showed a significantly higher plasma level of LPA in patients with a higher platelet concentration (group B) in comparison to those in group A (p < 0.05). This different concentration was evidenced in PRP but not in the clots. Depending on the number of platelets in patient's blood, a PRP-clot with higher or lower mechanical properties can be obtained. The higher level of LPA in PRP from patients richer in platelets should be considered as responsible for the higher hOB activity in bone regeneration.

ICOS-Ligand Triggering Impairs Osteoclast Differentiation and Function In Vitro and In Vivo.

Osteoblasts, osteocytes, and osteoclasts (OCs) are involved in the bone production and resorption, which are crucial in bone homeostasis. OC hyperactivation plays a role in the exaggerated bone resorption of diseases such as osteoporosis, rheumatoid arthritis, and osteolytic tumor metastases. This work stems from the finding that OCs can express B7h (ICOS-Ligand), which is the ligand of the ICOS T cell costimulatory molecule. Because recent reports have shown that, in endothelial, dendritic, and tumor cells, B7h triggering modulates several activities of these cells, we analyzed the effect of B7h triggering by recombinant ICOS-Fc on OC differentiation and function. The results showed that ICOS-Fc inhibits RANKL-mediated differentiation of human monocyte-derived OC-like cells (MDOCs) by inhibiting the acquirement of the OC morphology, the CD14- cathepsin K+ phenotype, and the expression of tartrate-resistant acid phosphatase, OSCAR, NFATc1, and DC-STAMP. Moreover, ICOS-Fc induces a reversible decrease in the sizes of cells and nuclei and cathepsin K expression in mature MDOCs. Finally, ICOS-Fc inhibits the osteolytic activities of MDOCs in vitro and the development of bone loss in ovariectomized or soluble RANKL-treated mice. These findings open a novel field in the pharmacological use of agonists and antagonists of the ICOS-B7h system.

Effect of retinoic acid and vitamin D3 on osteoblast differentiation and activity in aging.

Several studies have evidenced that in aging, osteoblast functional activity is impaired: osteoblast proliferation is slower and matrix deposition is less efficient. Because peroxisome-proliferator-activated receptor γ2 (PPARγ2) and fatty acids are important inhibitory signals in osteoblast development, we have investigated in human primary osteoblasts obtained from patients of different ages, the influence of retinoic acid and calcitriol on enzymes involved in differentiative (PPARγ2, ß-catenin, and insulin-like growth factor 1) and metabolic (carnitine palmitoyltransferase 1) intracellular pathways, and on transglutaminase 2, as enzyme fundamental for stabilizing the newly deposited extracellular matrix in bone. Retinoic acid and calcitriol influenced, respectively, proliferation and differentiation of osteoblasts, and an increase in PPARγ2 expression was observed following retinoic acid administration, whereas a decrease was observed following calcitriol administration. Aging widely influenced all parameters analyzed (the proliferation, differentiation, and new matrix deposition are significantly reduced in aged osteoblasts), with the exception of PPARγ2, which we found to be constitutively overexpressed and not modulated by retinoic acid or calcitriol administration. Our findings show the impaired ability of aged osteoblasts to perform adequate functional response and draw attention to the therapeutic approaches for bone healing in elderly patients.

Equisetum arvense standardized dried extract hinders age-related osteosarcopenia.

Age-associated osteosarcopenia is an unresolved syndrome characterized by the concomitant loss of bone (osteopenia) and skeletal muscle (sarcopenia) tissues increasing falls, immobility, morbidity, and mortality. Unbalanced resorption of bone in the remodeling process and excessive protein breakdown, especially fast type II myosin heavy chain (MyHC-II) isoform and myofiber metabolic shift, are the leading causes of bone and muscle deterioration in the elderly, respectively. Equisetum arvense (EQ) is a plant traditionally recommended for many pathological conditions due to its anti-inflammatory properties. Thus, considering that a chronic low-grade inflammatory state predisposes to both osteoporosis and sarcopenia, we tested a standardized hydroalcoholic extract of EQ in in vitro models of muscle atrophy [C2C12 myotubes treated with proinflammatory cytokines (TNFα/IFNγ), excess glucocorticoids (dexamethasone), or the osteokine, receptor activator of nuclear factor kappa-B ligand (RANKL)] and osteoclastogenesis (RAW 264.7 cells treated with RANKL). We found that EQ counteracted myotube atrophy, blunting the activity of several pathways depending on the applied stimulus, and reduced osteoclast formation and activity. By in silico target fishing, IKKB-dependent nuclear factor kappa-B (NF-κB) inhibition emerges as a potential common mechanism underlying EQ's anti-atrophic effects. Consumption of EQ (500 mg/kg/day) by pre-geriatric C57BL/6 mice for 3 months translated into: i) maintenance of muscle mass and performance; ii) restrained myofiber oxidative shift; iii) slowed down age-related modifications in osteoporotic bone, significantly preserving trabecular connectivity density; iv) reduced muscle- and spleen-related inflammation. EQ can preserve muscle functionality and bone remodeling during aging, potentially valuable as a natural treatment for osteosarcopenia.

Effects and differentiation activity of IGF-I, IGF-II, insulin and preptin on human primary bone cells.

The importance of the complex interrelated regulatory pathways involving IGF factors and pancreatic hormones can be observed in several metabolic diseases, where the deregulation of these factors has a wide impact on bone health. These findings have stimulated us to compare the effect of IGF-I, IGF-II, insulin and preptin on human bone cells. The effect on cell differentiation and cell activity of osteoblasts and osteoclasts has been analysed. We have observed a significant effect by IGF-I, a modest effect by IGF-II and preptin and no effect after insulin administration on human primary osteoblast-like cells. All studied factors have shown an induction on human primary osteoclast differentiation and bone resorption activity, with IGF-I being the most potent factor. We hypothesize that these findings may be on the basis of decreased bone mass density observed in several diseases.

MMP-2 Silencing through siRNA Loaded Positively-Charged Nanoparticles (AcPEI-NPs) Counteracts Chondrocyte De-Differentiation.

The abnormal matrix remodeling process, as well as inflammation, angiogenesis, and tumor metastasis, are related to an increase in the synthesis and secretion of matrix metalloproteinases (MMPs), the zinc-dependent proteolytic endopeptidases. Recent studies have evidenced MMPs' role in osteoarthritis (OA) development, during which chondrocytes undergo hypertrophic differentiation and exhibit enhanced catabolism. The trait of OA is extracellular matrix (ECM) progressive degradation regulated by many factors, in which MMPs play an important role, which indicates them as potential therapeutic targets. Herein, a small interfering RNA (siRNA) delivery system able to suppress MMPs' activity was synthetized. Results demonstrated that positively charged nanoparticles (AcPEI-NPs) complexed with MMP-2 siRNA are efficiently internalized by cells with endosomal escape. Moreover, avoiding lysosome degradation, MMP2/AcPEI nanocomplex increases nucleic acid delivery efficiency. Gel zymography, RT-PCR, and ELISA analyses confirmed MMP2/AcPEI nanocomplex activity even when embedded within collagen matrix resembling the natural extracellular matrix. Further, the inhibition of in vitro collagen degradation exerts a protective effect on chondrocyte dedifferentiation. The suppression of MMP-2 activity, preventing matrix degradation, protects chondrocytes against degeneration and supporting ECM homeostasis in articular cartilage. These encouraging results promote further investigation to validate the utilization of MMP-2 siRNA as ''molecular switch'' able to counteract osteoarthritis.

Isocyanides in med chem: A scaffold hopping approach for the identification of novel 4-isocyanophenylamides as potent antibacterial agents against methicillin-resistant Staphylococcusaureus.

We describe the rational use of the neglected isocyano moiety as pharmacophoric group for the design of novel 4-isocyanophenylamides as antibacterial agents. This class of novel compounds showed to be highly effective against methicillin resistant Staphylococcus aureus strains. In particular, from an extensive screening, we identified compound 42 as lead compound. It has shown a potent antimicrobial activity, an additive effect with most antibiotics currently in use, the ability not to induce the formation of resistant strains after ten passages, and the ability to block the biofilm formation. A nontoxic profile on mammalian cells and a proper metabolic stability on human liver microsome complete the picture of this new weapon against methicillin resistant Staphylococcus aureus infections.

Lipoaspirate Shows In Vitro Potential for Wound Healing.

Mesenchymal stem cells (MSCs) are a promising therapy in wound healing, although extensive time and manipulation are necessary for their use. In our previous study on cartilage regeneration, we demonstrated that lipoaspirate acts as a natural scaffold for MSCs and gives rise to their spontaneous outgrowth, together with a paracrine effect on resident cells that overcome the limitations connected to MSC use. In this study, we aimed to investigate in vitro whether the microfragmented adipose tissue (lipoaspirate), obtained with Lipogems® technology, could promote and accelerate wound healing. We showed the ability of resident cells to outgrow from the clusters of lipoaspirate encapsulated in a 3D collagen substrate as capability of repopulating a culture of human skin. Moreover, we demonstrated that the in vitro lipoaspirate paracrine effect on fibroblasts and keratinocytes proliferation, migration, and contraction rate is mediated by the release of trophic/reparative proteins. Finally, an analysis of the paracrine antibacterial effect of lipoaspirate proved its ability to secrete antibacterial factors and its ability to modulate their secretion in culture media based on a bacterial stimulus. The results suggest that lipoaspirate may be a promising approach in wound healing showing in vitro regenerative and antibacterial activities that could improve current therapeutic strategies.

Thermo-Responsive Gel Containing Hydroxytyrosol-Chitosan Nanoparticles (Hyt@tgel) Counteracts the Increase of Osteoarthritis Biomarkers in Human Chondrocytes.

Although osteoarthritis (OA) is a chronic inflammatory degenerative disease affecting millions of people worldwide, the current therapies are limited to palliative care and do not eliminate the necessity of surgical intervention in the most severe cases. Several dietary and nutraceutical factors, such as hydroxytyrosol (Hyt), have demonstrated beneficial effects in the prevention or treatment of OA both in vitro and in animal models. However, the therapeutic application of Hyt is limited due to its poor bioavailability following oral administration. In the present study, a localized drug delivery platform containing a combination of Hyt-loading chitosan nanoparticles (Hyt-NPs) and in situ forming hydrogel have been developed to obtain the benefits of both hydrogels and nanoparticles. This thermosensitive formulation, based on Pluronic F-127 (F-127), hyaluronic acid (HA) and Hyt-NPs (called Hyt@tgel) presents the unique ability to be injected in a minimally invasive way into a target region as a freely flowing solution at room temperature forming a gel at body temperature. The Hyt@tgel system showed reduced oxidative and inflammatory effects in the chondrocyte cellular model as well as a reduction in senescent cells after induction with H2O2. In addition, Hyt@tgel influenced chondrocytes gene expression under pathological state maintaining their metabolic activity and limiting the expression of critical OA-related genes in human chondrocytes treated with stressors promoting OA-like features. Hence, it can be concluded that the formulated hydrogel injection could be proposed for the efficient and sustained Hyt delivery for OA treatment. The next step would be the extraction of "added-value" bioactive polyphenols from by-products of the olive industry, in order to develop a green delivery system able not only to enhance the human wellbeing but also to promote a sustainable environment.

KYMASIN UP Natural Product Inhibits Osteoclastogenesis and Improves Osteoblast Activity by Modulating Src and p38 MAPK.

The imbalance in osteoblast (OB)-dependent bone formation in favor of osteoclast (OC)-dependent bone resorption is the main cause of loss of tissue mineral mass during bone remodeling leading to osteoporosis conditions. Thus, the suppression of OC activity together with the improvement in the OB activity has been proposed as an effective therapy for maintaining bone mass during aging. We tested the new dietary product, KYMASIN UP containing standardized Withania somnifera, Silybum marianum and Trigonella foenum-graecum herbal extracts or the single extracts in in vitro models mimicking osteoclastogenesis (i.e., RAW 264.7 cells treated with RANKL, receptor activator of nuclear factor kappa-Β ligand) and OB differentiation (i.e., C2C12 myoblasts treated with BMP2, bone morphogenetic protein 2). We found that the dietary product reduces RANKL-dependent TRAP (tartrate-resistant acid phosphatase)-positive cells (i.e., OCs) formation and TRAP activity, and down-regulates osteoclastogenic markers by reducing Src (non-receptor tyrosine kinase) and p38 MAPK (mitogen-activated protein kinase) activation. Withania somnifera appears as the main extract responsible for the anti-osteoclastogenic effect of the product. Moreover, KYMASIN UP maintains a physiological release of the soluble decoy receptor for RANKL, OPG (osteoprotegerin), in osteoporotic conditions and increases calcium mineralization in C2C12-derived OBs. Interestingly, KYMASIN UP induces differentiation in human primary OB-like cells derived from osteoporotic subjects. Based on our results, KYMASIN UP or Withania somnifera-based dietary supplements might be suggested to reverse the age-related functional decline of bone tissue by re-balancing the activity of OBs and OCs, thus improving the quality of life in the elderly and reducing social and health-care costs.

Biomimetic Citrate-Coated Luminescent Apatite Nanoplatforms for Diclofenac Delivery in Inflammatory Environments.

Luminescent nanoparticles are innovative tools for medicine, allowing the imaging of cells and tissues, and, at the same time, carrying and releasing different types of molecules. We explored and compared the loading/release ability of diclofenac (COX-2 antagonist), in both undoped- and luminescent Terbium3+ (Tb3+)-doped citrate-coated carbonated apatite nanoparticles at different temperatures (25, 37, 40 °C) and pHs (7.4, 5.2). The cytocompatibility was evaluated on two osteosarcoma cell lines and primary human osteoblasts. Biological effects of diclofenac-loaded-nanoparticles were monitored in an in vitro osteoblast's cytokine-induced inflammation model by evaluating COX-2 mRNA expression and production of PGE2. Adsorption isotherms fitted the multilayer Langmuir-Freundlich model. The maximum adsorbed amounts at 37 °C were higher than at 25 °C, and particularly when using the Tb3+ -doped particles. Diclofenac-release efficiencies were higher at pH 5.2, a condition simulating a local inflammation. The luminescence properties of diclofenac-loaded Tb3+ -doped particles were affected by pH, being the relative luminescence intensity higher at pH 5.2 and the luminescence lifetime higher at pH 7.4, but not influenced either by the temperature or by the diclofenac-loaded amount. Both undoped and Tb3+-doped nanoparticles were cytocompatible. In addition, diclofenac release increased COX-2 mRNA expression and decreased PGE2 production in an in vitro inflammation model. These findings evidence the potential of these nanoparticles for osteo-localized delivery of anti-inflammatory drugs and the possibility to localize the inflammation, characterized by a decrease in pH, by changes in luminescence.

Osteosynthesis devices in absorbable Magnesium alloy in comparison to standard ones: a Systematic Review on effectiveness and safety.

BACKGROUND AND AIM OF THE WORK: Magnesium (Mg) is a metal physiologically present in bone tissue and essential for bone health. Mg-based-alloys exhibit mechanical properties, namely density and strength, similar to human cortical bone. These features have been exploited for the development of osteosynthesis devices in biodegradable Mg-based-alloys. Accordingly, the aim of this study was to rank the effectiveness and safety of Mg-based alloys applied in bone surgery in comparison to other suitable metals, focusing in particular on Mg superior biocompatibility and biodegradability. METHODS: a systematic-review of the literature was conducted including only primary research studies dealing with patients suffering from fractured or osteotomized bones fixed using Mg-based osteosynthesis-devices. RESULTS: literature revision suggested Mg-alloys holding comparable properties and side effects in comparison with titanium (Ti) screws, thus showing similar efficacy and safety. In particular, the gas formation in the carpal bones was identified as the main side effect of the Mg-alloys, during the corrosion/degradation phase of Mg. CONCLUSIONS: according to the considered literature, the main advantages exploiting Mg-alloys for bone implants are related to their biocompatibility, bio-absorbability/-degradability, the lack of surgical removal, osteoconductivity and antibacterial activity. On the opposite, the main limitation of Mg-alloys is due to the poor mechanical resistance of small devices for internal fixation of bone fragments that lack of sufficient strength to withstand high forces. Therefore, an important future prospect could rely in the development of innovative hybrid systems aimed at fixing high load-bearing fractures, as well as in regenerative-medicine by developing new Mg-based engineered scaffolds.

Counter-Acting Candida albicans-Staphylococcus aureus Mixed Biofilm on Titanium Implants Using Microbial Biosurfactants.

This study aimed to grow a fungal-bacterial mixed biofilm on medical-grade titanium and assess the ability of the biosurfactant R89 (R89BS) coating to inhibit biofilm formation. Coated titanium discs (TDs) were obtained by physical absorption of R89BS. Candida albicans-Staphylococcus aureus biofilm on TDs was grown in Yeast Nitrogen Base, supplemented with dextrose and fetal bovine serum, renewing growth medium every 24 h and incubating at 37 °C under agitation. The anti-biofilm activity was evaluated by quantifying total biomass, microbial metabolic activity and microbial viability at 24, 48, and 72 h on coated and uncoated TDs. Scanning electron microscopy was used to evaluate biofilm architecture. R89BS cytotoxicity on human primary osteoblasts was assayed on solutions at concentrations from 0 to 200 µg/mL and using eluates from coated TDs. Mixed biofilm was significantly inhibited by R89BS coating, with similar effects on biofilm biomass, cell metabolic activity and cell viability. A biofilm inhibition >90% was observed at 24 h. A lower but significant inhibition was still present at 48 h of incubation. Viability tests on primary osteoblasts showed no cytotoxicity of coated TDs. R89BS coating was effective in reducing C. albicans-S. aureus mixed biofilm on titanium surfaces and is a promising strategy to prevent dental implants microbial colonization.

Regulation of osteoblast and osteoclast functions by FGF-6.

Fibroblast growth factor-6 (FGF-6) is known to be the key ligand for fibroblast growth factor receptor 4 (FGFR4) during muscle regeneration but its role in bone has yet to be verified. FGFR signaling is known to be important in the initiation and regulation of osteogenesis, so in this study the actions of FGF-6 on human osteoblasts and osteoclasts were investigated. Human primary osteoblasts (hOB) were used to study the effect of FGF-6 on proliferation (by ATP quantification), signal transduction (by ERK and AKT phosphorylation), differentiation (by alkaline phosphatase activity, APA), and mineralization (by calcein staining). To study FGF-6 activity on osteoclast differentiation, human bone marrow cells were used and tartrate-resistant acid phosphatase (TRAP) multinucleated cells together with actin filaments arrangements were quantified. Human primary mature osteoclasts were used to evaluate the effect of FGF-6 on osteoclast reabsorbing activity by reabsorbed pit measurements. FGF-6 >10(-9) M as FGF-2 10(-7) M induced hOB proliferation mediated by pERK together with a reduction in APA and reduced mineralization of the treated cells. Moreover FGF-6 increased the formation of TRAP-positive multinucleated cells in a dose-dependent manner (maximal effect at 10(-8) M). FGF-6-treated cells showed also a greater percentage of cells that formed typical osteoclast sealing zones. Mature osteoclasts cultured on dentine slice increased the area of reabsorption with a maximal effect of FGF-6 at 10(-12) M. FGF-6 may be considered a regulator of bone metabolism as shown by its activity on both osteoblasts and osteoclasts.

Controlled delivery of the heparan sulfate/FGF-2 complex by a polyelectrolyte scaffold promotes maximal hMSC proliferation and differentiation.

Growth factors and other regulatory molecules are required to direct differentiation of bone marrow-derived human mesenchymal stem cells (hMSC) along specific lineages. However, the therapeutic use of growth factors is limited by their susceptibility to degradation, and the need to maintain prolonged local release of growth factor at levels sufficient to stimulate hMSC. The aim of this study was to investigate whether a device containing heparan sulfate (HS), which is a co-factor in growth factor-mediated cell proliferation and differentiation, could potentiate and prolong the delivery of fibroblast growth factor-2 (FGF-2) and thus enhance hMSC stimulation. To this aim, we synthesized cationic polyelectrolyte polymers covalently and non-covalently anchored to HS and evaluated their effect on hMSC proliferation. Polymers non-covalently bound to HS resulted in the release of an HS/FGF-2 complex rather than FGF-2 alone. The release of this complex significantly restored hMSC proliferation, which was abolished in serum-free medium and only partially restored by the release of FGF-2 alone as occurred with polymer covalently bound to HS. We also demonstrate that exposure to HS/FGF-2 during early growth but not during post-confluence is essential for hMSC differentiation down the fibroblast lineage, which suggests that both factors are required to establish the correct stem cell commitment that is necessary to support subsequent differentiation. In conclusion, the delivery platform described here is a step towards the development of a new class of biomaterial that enables the prolonged, non-covalent binding and controlled delivery of growth factors and cofactors without altering their potency.

Autologous Platelet Rich Plasma (PRP) in the treatment of elbow epicondylitis and plantar fasciitis: medium to long term clinical outcome.

BACKGROUND AND AIM: Platelet-Rich-Plasma (PRP) is a popular biological therapy especially used to regenerate different musculoskeletal tissues by releasing growth-factors and cytokines promoting cell proliferation, chemotaxis, differentiation, and angiogenesis. The aim was to evaluate the clinical effectiveness and safety of PRP for Lateral-Epicondylitis (LE) of the elbow and Plantar-Fasciitis (PF). METHODS: A retrospective study was conducted including patients treated with a single topic autologous-PRP-injection between 1-1-2009 and 7-18-2019 for LE or PF at our institution; patients operated for the same problem, patients refusing the study or not traceable were excluded. Patients were assessed with VAS for pain and clinical scales. RESULTS: 33 patients were treated with PRP and 13 (8F, 5M) included: 4LE and 9PF for a total of 16 cases. The average pain level was 0.61±0.63: 1±1.41 for LE and 0,44±0 for PF. No significant side effect was reported. 4 PRP-treatments failed: 2LE and 2PF. OES and PRTEE gave excellent results for elbow. Average foot scores were AOFAS 98.2±5 and FADI 91.3±1. Patients were stratified and compared according to plantar arch conformation, follow-up length, healing time, time from diagnosis to PRP-treatment, therapies before PRP (physiotherapy, steroid infiltration or shock-waves), risk factors (standing work, sport, age, sex). CONCLUSIONS: As in other studies, our results do not allow to draw sufficiently valid conclusions regarding the effectiveness and safety of PRP in the treatment of LE and PF: in particular the statistical significance is limited by the small sample size. PRP can be chosen as a non-first-line treatment for LE and PF.

Translation, cross-cultural adaptation, reliability, and validation of the italian version of the Foot and Ankle Disability Index (FADI).

BACKGROUND AND AIM OF THE WORK: Foot-and-Ankle-Disability-Index (FADI) is one of the most widely used evaluation questionnaires for this anatomical district, but an italian validated version lacks and is necessary to properly evaluate italian people. In fact a correct interpretation of the items by patients is essential to obtain a precise subjective response, making the questionnaire valid to evaluate patients' satisfaction and wellness. Our purpose was to translate and culturally adapt into Italian the FADI questionnaire, and to check its reproducibility and validity. MATERIALS AND METHODS: The original english version of FADI questionnaire was translated into Italian and checked for medical part coherence. It was submitted to 10 italian randomized patients to verify a correct cultural adaptation, and then to other 50 randomized patients operated at their ankle or hallux to assess intra- and inter-observer reproducibility by the Pearson's-Correlation-Coefficient (PCC) and the Intra-Class-Correlation (ICC) coefficient. Moreover, Short-Form-36 (SF36) questionnaire for Quality-of-Life and Visual-Analogue-Scale (VAS) for pain were also administered to the same 60 people and compared to italian-FADI to perform validation analysis by PCC and ICC coefficient. RESULTS: Cultural adaptation of the translated version of the scale resulted good in terms of understandability by patients. An optimal correlation of the inter- and intra-observer reproducibility was obtained. The correlation obtained between FADI and SF-36 as well as between FADI and VAS indicates success in the validation process. CONCLUSIONS: Validation of the FADI italian version has been performed successfully, its use can be considered appropriate and is indicated in italian clinical practice. (www.actabiomedica.it).

Injectable Scaffolds Enriched with Silver to Inhibit Bacterial Invasion in Tissue Regeneration.

During wound healing, bacterial infections may prolong skin regeneration and tissue repair, causing delayed or incomplete healing. The therapeutic strategies currently used include general therapeutic modes, growth factors, skin substitutes, matrices and/or cell therapy. Among recent technologies, wound dressing materials comprising silver nitrate or silver sulfadiazine as the antimicrobial agent are widespread, despite their known cytotoxicity. The aim of this work was to develop and evaluate the efficacy of gelatinous injectable biomaterials composed of collagen and alginates, enriched with silver against bacterial pathogens commonly involved in wound infections. To reduce cytotoxicity, silver was used as lactate and saccharinated salts. Results show that silver-enriched beads were effective against both Gram-positive and Gram-negative strains in a concentration-dependent manner. Silver addition was more active against Staphylococcus epidermidis than against Pseudomonas aeruginosa. The antibacterial activity was localized only in the area of contact with the beads at concentrations lower than 0.3 mM, whereas at higher concentrations a larger inhibition halo was observed. No cytotoxic effect on eukaryotic cells was seen both testing the materials' extracts or the Ag-doped beads in contact tests. These results, although preliminary, suggest that these scaffolds are a promising approach for realizing injectable or spreadable functional biomaterials with antibacterial activity for applications in wound management.