Inflammation is an important biological process to be considered in designing successful biomaterial-based therapeutics. Indeed, prolonged inflammation can result in delayed wound healing and, in some cases, may cause the rejection of the biomaterial together with additional tissue damage. Mesenchymal stem cells (MSCs) participate in this critical intercellular communication to modulate bone healing. In this study, MSCs were employed as in vitro model in order to evaluate the biological performances, in terms of immune response, of Bio-Oss®/Avitene™ composite scaffold. Moreover, new bone formation was evaluated in patients undergoing maxillomandibular osteotomy for skeletal malocclusion, facial asymmetry, or aesthetic indications, using a Bio-Oss®/Avitene™ composite scaffold. The early inflammatory response of human bone marrow derived-mesenchymal stem cells (BM-MSCs) was investigated in vitro analysing the gene expression of IL-6 and IL-8 using Droplet Digital PCR and the release of cytokines, chemokines, and growth factors using Bio-Plex approach. Clinical evaluation was performed using Cone Beam Computed Tomography (CBCT). In vitro, Bio-Oss®/Avitene™ decreases the IL-6 expression, quantified with Droplet Digital PCR approach. Bio-Plex reveals that the protein levels of MCP-1 and IL-6 were reduced, while IL-4, IL-8 and VEGF were increased by the scaffold in cells up to day 7. CBCT assessment in patients demonstrated stable outcomes, supporting the potential for long-term aesthetic restoration of the zygomatic region. These findings indicate that Bio-Oss®/Avitene™ possesses immunomodulatory potential and is capable of directing anti-inflammatory, immune-mediated responses associated with bone regrowth for the treatment of dentofacial deformities through orthognathic surgery.

Osteosarcoma (OS) is an aggressive primary bone tumour with high metastatic potential. Current treatments including surgery and chemotherapy are limited by side effects and chemoresistance, underscoring the need for novel therapies. This study aimed to investigate the antitumor potential of resveratrol (RSV), a natural polyphenol, as a novel treatment for OS. The effects of RSV were evaluated in two osteosarcoma cell lines (SAOS-2 and U2-OS). A viability assay established 100 μM as the effective concentration, and hyperspectral imaging confirmed cellular uptake. Apoptosis was measured via caspase-3/7 activity and Annexin V/PI staining, while qRT-PCR assessed pro-apoptotic gene expression. Flow cytometry evaluated cell-cycle progression, and a wound-healing assay measured migration. Gene expression analyses (qRT-PCR) examined markers of cell adhesion, tumour progression and epithelial-mesenchymal transition. Finally, RSV's impact on the Wnt/β-catenin pathway was determined by quantifying nuclear β-catenin accumulation and the expression of its downstream oncogenic targets. RSV inhibited cell proliferation and induced apoptosis, increasing caspase-3/7 activity and modulating apoptotic gene expression. RSV also caused cell cycle arrest in S-phase. It reduced the cells' migration and altered the expression of cell adhesion and tumour progression genes, promoting a less invasive phenotype. Notably, RSV decreased nuclear β-catenin accumulation, downregulated oncogenic targets like c-Myc and MMPs, and upregulated E-cadherin while reducing vimentin levels, suggesting a reversal of epithelial-mesenchymal transition. These results suggest that RSV may offer a promising therapeutic approach for osteosarcoma, modulating key pathways involved in tumour progression, metastasis and chemoresistance. Further studies are required to assess its clinical applicability.

Merkel cells are specialized oval-shaped epithelial cells located in the basal epidermis and hair follicles, connected with afferent nerve endings responsible for sensory perception of light touch. Recent advances in developmental biology have shed light on the complex regulatory networks governing Merkel cell maturation. The most recent evidence indicates a crosstalk among epigenetic pathways, notably Polycomb multi-subunit complexes, Merkel cell-lineage transcription factors such as atonal BHLH transcription factor 1 (ATOH1), SRY-box transcription factor 2 (SOX2), ISL LIM homeobox 1 (ISL1) and additional players in the regulation of Merkel cell developmental programs. At the same time, the implications of dysregulated Merkel cell-lineage transcription factors during Merkel cell carcinoma (MCC) onset is under investigation. This review offers a comprehensive overview of the current understanding of the genetic and epigenetic pathways crucial for Merkel cell differentiation. It covers the implication of Merkel cell-specific developmental programs, the role of epigenetic regulatory Polycomb complexes, and how genetic and epigenetic mechanisms converge to orchestrate Merkel cell differentiation.

The increasing incidence of bone diseases has driven research towards Bone Tissue Engineering (BTE), an innovative discipline that uses biomaterials to develop three-dimensional (3D) scaffolds capable of mimicking the natural environment of bone tissue. Traditional approaches relying on two-dimensional (2D) models have exhibited significant limitations in simulating cellular interactions and the complexity of the bone microenvironment. In response to these challenges, 3D models such as organoids and cellular spheroids have emerged as effective tools for studying bone regeneration. Adult mesenchymal stem cells have proven crucial in this context, as they can differentiate into osteoblasts and contribute to bone tissue repair. Furthermore, the integration of composite biomaterials has shown substantial potential in enhancing bone healing. Advanced technologies like microfluidics offer additional opportunities to create controlled environments for cell culture, facilitating more detailed studies on bone regeneration. These advancements represent a fundamental step forward in the treatment of bone pathologies and the promotion of skeletal health. In this review, we report on the evolution of in vitro culture models applied to the study of bone healing/regrowth, starting from 2 to 3D cultures and microfluids. The different methodologies of in vitro model generation, cells and biomaterials are presented and discussed.

Bone diseases represent a growing healthcare challenge due to population aging and lifestyle changes. Although bone has a natural regenerative capacity, approximately 10% of fractures fail to heal properly, requiring advanced therapeutic approaches. Bone tissue engineering (BTE) has advanced the use of osteoinductive and osteoconductive biomaterials to support bone regeneration. Among them, Bio-Oss® Collagen, a composite of bovine hydroxyapatite and collagen, has shown excellent biocompatibility and bioactivity properties. This study analyzes the effect of Bio-Oss® Collagen on human bone marrow-derived mesenchymal stem cells (hBMSCs), assessing its osteoinductive and immunomodulatory potential. After 7 days of culture, the biomaterial modulated the expression of key genes involved in osteogenesis and chondrogenesis, which are known for their role in bone formation and maturation. At the same time, a downregulation of genes associated with bone resorption was observed. Secretome analysis revealed a controlled release of pro-regenerative cytokines, suggesting a role of the biomaterial in modulating inflammation to promote bone regeneration. Furthermore, immunofluorescence confirmed the high expression of osteocalcin and osteopontin, which are key markers of bone mineralization. These findings indicate that Bio-Oss® Collagen supports osteogenesis and modulates the immune response, creating a microenvironment favorable for bone regeneration.

Background: Pleural mesothelioma (PM) is a rare and highly aggressive tumor, primarily caused by asbestos exposure. Its long latency period and late-stage diagnosis severely limit therapeutic options. Aim: Recent evidence suggests that non-coding RNAs (ncRNAs)—including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)—play key roles in PM biology. This review aims to synthesize current knowledge on ncRNA dysregulation in PM and explore their diagnostic, prognostic, and therapeutic potential. Scope: We summarize studies addressing the expression and function of ncRNAs in tumors and in circulating biofluids of PM patients. Particular attention is given to how ncRNAs regulate proliferation, apoptosis, and migration, and how competing endogenous RNA (ceRNA) networks shape gene regulation in PM. Novelty and Conclusion: Unlike previous reviews, this work integrates findings across different classes of ncRNAs and their interactions, highlighting the emerging concept of ceRNA networks in PM. By bridging molecular mechanisms with potential clinical applications, we provide an updated and comprehensive framework that may inform future strategies for diagnosis, prognosis, and targeted therapy in PM.

Pleural Mesothelioma (PM) is an aggressive tumor with a poor prognosis and limited therapeutic options. Despite the notion that resveratrol (RSV) significantly inhibits the growth of PM cancer cells, it is necessary to evaluate the effects of this stilbene as a tumor suppressor agent. In this work, the effects of the natural polyphenol were investigated on PM cell lines (MSTO-211H and IST-MES 2) to evaluate its action as a potential adjuvant agent, together with chemotherapy. Our results showed that RSV treatment was effective in PM cell lines, in particular in MSTO-211H. RES treatment decreases the viability evaluated with the MTT assay and Live/Dead staining. RSV stimulates the apoptotic process with positive staining for Annexin V-PI and Caspase-3/7 and inhibits the migration ability of both PM cell lines. In IST-MES 2, RSV causes a reduction in mitochondrial and cytoplasmic calcium levels. Moreover, RSV affects cellular morphology, E-cadherin protein expression, and decreased nuclear localization of β-catenin, attenuating Wnt/β-catenin signaling, which regulates tumor cell proliferation. At the molecular level, RSV modulated the expression of key genes that play an important role in cellular adhesion, proliferation, and metabolic activity, as well as AMPK signaling. RSV seems to be a promising therapeutic adjuvant agent for PM treatment.

Bone regeneration has emerged as a critical research and clinical advancement field, fueled by the growing demand for effective treatments in orthopedics and oncology. Over the past two decades, significant progress in biomaterials and surgical techniques has led to the development of novel solutions for treating bone defects, surpassing the use of traditional autologous grafts. This review aims to assess the latest approaches in bone regeneration, including autologous, allogenic, and xenogenic grafts, naturally derived biomaterials, and innovative synthetic substitutes such as bioceramics, bioactive glasses, metals, polymers, composite materials, and other specialized applications. A comprehensive literature search was conducted on PubMed, focusing on studies published between 2019 and 2024, including meta-analyses, reviews, and systematic reviews. The review evaluated a range of bone regeneration strategies, examining the clinical outcomes, materials used, surgical techniques, and the effectiveness of various approaches in treating bone defects. The search identified numerous studies, with the inclusion criteria focused on those exploring innovative bone regeneration strategies. These studies provided valuable insights into the clinical and biological outcomes of different biomaterials and graft types. Results indicated that while advancements in synthetic and naturally derived biomaterials show promising potential, challenges remain in optimizing therapeutic strategies across diverse patient populations and clinical settings. The findings emphasize the need for an integrated approach that combines scientific research, clinical practice, and technological innovation to improve bone regeneration therapies. Further research is required to establish standardized protocols and determine the optimal application of various materials and techniques to enhance patient outcomes and the quality of care.

IntroductionHuman polyomaviruses (HPyVs) cause persistent/latent infections in a large fraction of the population. HPyV infections may cause severe diseases in immunocompromised patients. Malawi polyomavirus (MWPyV) is the 10th discovered human polyomavirus (HPyV 10). MWPyV was found in stool samples of healthy children. So far, the few investigations carried out on HPyV 10 did not find an association with human disease.MethodsIn this study, to verify the putative association between MWPyV and human diseases, MWPyV seroprevalence was investigated in patients affected by i) lymphoproliferative disorders (LPDs) and ii) immune system disorders, i.e., autoimmune diseases (ADs), and in iii) healthy subjects. An indirect ELISA, employing virus-like particles (VLPs) to detect serum IgG antibodies against MWPyV/HPyV 10, was carried out. The study also revealed the prevalence of another polyomavirus, Merkel cell polyomavirus (MCPyV).ResultsSera from patients with distinct autoimmune diseases (n = 44; mean age 20 years) had a prevalence of MWPyV antibodies of 68%, while in patients with lymphoproliferative disorders (n = 15; mean age 14 years), subjected to bone marrow transplantation, the prevalence was 47%. In healthy subjects (n = 66; mean age 13 years), the prevalence of MWPyV antibodies was 67%. Our immunological investigation indicates that MWPyV/HPyV 10 seroconversion occurs early in life and MWPyV/HPyV 10 appears to be another polyomavirus ubiquitous in the human population. A significantly lower MWPyV antibody reactivity together with a lower immunological profile was detected in the sera of LPD patients compared with HS2 (*p < 0.05) (Fisher’s exact test). LPD and AD patients have a similar MCPyV seroprevalence compared with healthy subjects.DiscussionMWPyV seroprevalence indicates that this HPyV is not associated with lymphoproliferative and autoimmune diseases. However, the ability to produce high levels of antibodies against MWPyV appears to be impaired in patients with lymphoproliferative disorders. Immunological investigations indicate that MWPyV seroconversion occurs early in life. MCPyV appears to be a ubiquitous polyomavirus, like other HPyVs, in the human population.

In this study, zeolitic imidazolate framework 8 (ZIF-8) was coated on porous Ti6Al4V scaffolds, either bare or previously modified using hydroxyapatite (HA) or HA and gelatin (HAgel), via a growing single-step method in aqueous media using two contact times at 6 h and 24 h. The coated scaffolds termed ZIF-8@Ti, ZIF-8@HA/Ti, and ZIF-8@HAgel/Ti were characterized via scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), and molecular plasma-atomic emission spectroscopy (MP-AES). In order to assess the cell proliferation rate, the cytocompatibility of the scaffolds was evaluated in primary osteoblasts (hOBs) using alamarBlue assay, while the osteoconductivity was analyzed in hOBs using a real-time approach, evaluating the expression of secreted phosphoprotein 1 (SPP1). Osteopontin, which is the protein encoded by this gene, represents the major non-collagenous bone protein that binds tightly to HA. The scaffolds were shown to be non-cytotoxic based on hOB proliferation at all time points of analysis (24 h and 72 h). In hOB cultures, the scaffolds induced the upregulation of SPP1 with different fold changes. Some selected scaffolds were assayed in vitro for their antibacterial potential against Staphylococcus epidermidis; the scaffolds coated with ZIF-8 crystals, regardless of the presence of HA and gelatin, strongly inhibited bacterial adhesion to the materials and reduced bacterial proliferation in the culture medium, demonstrating the suitable release of ZIF-8 in a bioactive form. These experiments suggest that the innovative scaffolds, tested herein, provide a good microenvironment for hOB adhesion, viability, and osteoconduction with effective prevention of S. epidermidis adhesion.

Osteosarcoma (OS) cancer treatments include systemic chemotherapy and surgical resection. In the last years, novel treatment approaches have been proposed, which employ a drug-delivery system to prevent offside effects and improves treatment efficacy. Locally delivering anticancer compounds improves on high local concentrations with more efficient tumour-killing effect, reduced drugs resistance and confined systemic effects. Here, the synthesis of injectable strontium-doped calcium phosphate (SrCPC) scaffold was proposed as drug delivery system to combine bone tissue regeneration and anticancer treatment by controlled release of methotrexate (MTX) and doxorubicin (DOX), coded as SrCPC-MTX and SrCPC-DOX, respectively. The drug-loaded cements were tested in an in vitro model of human OS cell line SAOS-2, engineered OS cell line (SAOS-2-eGFP) and U2-OS. The ability of doped scaffolds to induce OS cell death and apoptosis was assessed analysing cell proliferation and Caspase-3/7 activities, respectively. To determine if OS cells grown on doped-scaffolds change their migratory ability and invasiveness, a wound-healing assay was performed. In addition, the osteogenic potential of SrCPC material was evaluated using human adipose derived-mesenchymal stem cells. Osteogenic markers such as (i) the mineral matrix deposition was analysed by alizarin red staining; (ii) the osteocalcin (OCN) protein expression was investigated by enzyme-linked immunosorbent assay test, and (iii) the osteogenic process was studied by real-time polymerase chain reaction array. The delivery system induced cell-killing cytotoxic effects and apoptosis in OS cell lines up to Day 7. SrCPC demonstrates a good cytocompatibility and it induced upregulation of osteogenic genes involved in the skeletal development pathway, together with OCN protein expression and mineral matrix deposition. The proposed approach, based on the local, sustained release of anticancer drugs from nanostructured biomimetic drug-loaded cements is promising for future therapies aiming to combine bone regeneration and anticancer local therapy.

Bone is a unique type of mineralised connective tissue that can support and protect soft tissues, contain bone marrow, and allow movement [...]

The epigenetic role of microRNAs is established at both physiological and pathological levels. Dysregulated miRNAs and their targets appear to be a promising approach for innovative anticancer therapies. In our previous study, circulating miR-197-3p tested dysregulated in workers ex-exposed to asbestos (WEA). Herein, an epigenetic investigation on this circulating miRNA was carried out in sera from malignant pleural mesothelioma (MPM) patients. MiR-197-3p was quantified in MPM (n = 75) sera and comparatively analyzed to WEA (n = 75) and healthy subject (n = 75) sera, using ddPCR and RT-qPCR techniques. Clinicopathological characteristics, occupational, non-occupational information and overall survival (OS) were evaluated in correlation studies. MiR-197-3p levels, analyzed by ddPCR, were significantly higher in MPM than in WEA cohort, with a mean copies/µl of 981.7 and 525.01, respectively. Consistently, RT-qPCR showed higher miR-197-3p levels in sera from MPM with a mean copies/µl of 603.7, compared to WEA with 336.1 copies/µl. OS data were significantly associated with histologic subtype and pleurectomy. Circulating miR-197-3p is proposed as a new potential biomarker for an early diagnosis of the MPM onset. Indeed, miR-197-3p epigenetic investigations along with chest X-ray, computed tomography scan and spirometry could provide relevant information useful to reach an early and effective diagnosis for MPM.

Background Blood transfusions represent common medical procedures, which provide essential supportive therapy. However, these procedures are notoriously expensive for healthcare services and not without risk. The potential threat of transfusion-related complications, such as the development of pathogenic infections and the occurring of alloimmunization events, alongside the donor’s dependence, strongly limits the availability of transfusion units and represents significant concerns in transfusion medicine. Moreover, a further increase in the demand for donated blood and blood transfusion, combined with a reduction in blood donors, is expected as a consequence of the decrease in birth rates and increase in life expectancy in industrialized countries. Main body An emerging and alternative strategy preferred over blood transfusion is the in vitro production of blood cells from immortalized erythroid cells. The high survival capacity alongside the stable and longest proliferation time of immortalized erythroid cells could allow the generation of a large number of cells over time, which are able to differentiate into blood cells. However, a large-scale, cost-effective production of blood cells is not yet a routine clinical procedure, as being dependent on the optimization of culture conditions of immortalized erythroid cells. Conclusion In our review, we provide an overview of the most recent erythroid cell immortalization approaches, while also describing and discussing related advancements of establishing immortalized erythroid cell lines.

Stem cell-based therapy is a significant topic in regenerative medicine, with a predominant role being played by human mesenchymal stem cells (hMSCs). The hMSCs have been shown to be suitable in regenerative medicine for the treatment of bone tissue. In the last few years, the average lifespan of our population has gradually increased. The need of biocompatible materials, which exhibit high performances, such as efficiency in bone regeneration, has been highlighted by aging. Current studies emphasize the benefit of using biomimetic biomaterials, also known as scaffolds, for bone grafts to speed up bone repair at the fracture site. For the healing of injured bone and bone regeneration, regenerative medicine techniques utilizing a combination of these biomaterials, together with cells and bioactive substances, have drawn a great interest. Cell therapy, based on the use of hMSCs, alongside materials for the healing of damaged bone, has obtained promising results. In this work, several aspects of cell biology, tissue engineering, and biomaterials applied to bone healing/regrowth will be considered. In addition, the role of hMSCs in these fields and recent progress in clinical applications are discussed. Impact StatementThe restoration of large bone defects is both a challenging clinical issue and a socioeconomic problem on a global scale. Different therapeutic approaches have been proposed for human mesenchymal stem cells (hMSCs), considering their paracrine effect and potential differentiation into osteoblasts. However, different limitations are still to be overcome in using hMSCs as a therapeutic opportunity in bone fracture repair, including hMSC administration methods. To identify a suitable hMSC delivery system, new strategies have been proposed using innovative biomaterials. This review provides an update of the literature on hMSC/scaffold clinical applications for the management of bone fractures.

The aim of this study was to investigate whether the presence of Staphylococcus aureus (SA) producing the Panton-Valentine leukocidin (PVL) affects the outcome of Prosthetic Joint Infection (PJI). Patients with acute and chronic PJI sustained by SA were prospectively enrolled at the orthopedic unit of "Casa di Cura Santa Maria Maddalena", from January 2019 to October 2021. PJI diagnosis was reached according to the diagnostic criteria of the International Consensus Meeting on PJI of Philadelphia. Synovial fluid obtained via joint aspirations was collected in order to isolate SA. The detection of PVL was performed via real-time quantitative PCR (RT-qPCR). The outcome assessment was performed using the criteria of the Delphi-based International Multidisciplinary Consensus. Twelve cases of PJI caused by SA were included. Nine (75%) cases were acute PJI treated using debridement, antibiotic and implant retention (DAIR); the remaining three (25%) were chronic PJI treated using two-stage (n = 2) and one-stage revision (n = 1), respectively. The SA strains that tested positive for PVL genes were 5/12 (41.6%,). Treatment failure was documented in three cases of acute PJI treated using DAIR, all supported by SA-PVL strains (p < 0.045). The remaining two cases were chronic PJI treated with a revision arthroplasty (one and two stage, respectively), with a 100% eradication rate in a medium follow-up of 24 months. Although a small case series, our study showed a 100% failure rate in acute PJI, probably caused by SA PVL-producing strains treated conservatively (p < 0.04). In this setting, toxin research should guide radical surgical treatment and targeted antibiotic therapy.

Bone metabolism consists of a balance between bone formation and bone resorption, which is mediated by osteoblast and osteoclast activity, respectively. In order to ensure bone plasticity, the bone remodeling process needs to function properly. Mesenchymal stem cells differentiate into the osteoblast lineage by activating different signaling pathways, including transforming growth factor β (TGF-β)/bone morphogenic protein (BMP) and the Wingless/Int-1 (Wnt)/β-catenin pathways. Recent data indicate that bone remodeling processes are also epigenetically regulated by DNA methylation, histone post-translational modifications, and non-coding RNA expressions, such as micro-RNAs, long non-coding RNAs, and circular RNAs. Mutations and dysfunctions in pathways regulating the osteoblast differentiation might influence the bone remodeling process, ultimately leading to a large variety of metabolic bone diseases. In this review, we aim to summarize and describe the genetics and epigenetics of the bone remodeling process. Moreover, the current findings behind the genetics of metabolic bone diseases are also reported.

Resveratrol is a powerful antioxidant molecule. In the human diet, its most important source is in Vitis vinifera grape peel and leaves. Resveratrol exists in two isoforms, cis- and trans. The diastereomeric forms of many drugs have been reported as affecting their activity. The aim of this study was to set up a cellular model to investigate how far resveratrol could counteract cytotoxicity in an oxidant agent. For this purpose, a keratinocyte cell line, which was genetically engineered with jelly fish green fluorescent protein, was treated with the free radical promoter Cumene hydroperoxide. The antioxidant activity of the trans-resveratrol and its diastereomeric mixture was evaluated indirectly in these treated fluorescent-engineered keratinocytes by analyzing the cell number and cell proliferation index. Our results demonstrate that cells, which were pre-incubated with resveratrol, reverted the oxidative damage progression induced by this free radical agent. In conclusion, fluorescent-engineered human keratinocytes represent a rapid and low-cost cellular model to determine cell numbers by studying emitted fluorescence. Comparative studies carried out with fluorescent keratinocytes indicate that trans-resveratrol is more efficient than diastereomeric mixtures in protecting cells from the oxidative stress.

Purpose:The success of total joint arthroplasty (TJA) has led to consistent growth in the use of arthroplasty in progressively younger patients. However, more than 10 percent of patients require revision surgery due to implant failure caused by aseptic or septic inflammation. Among the latter, surgical site infection (SSI) represents one of the worst complications of TJA, potentially resulting in the removal of the prosthesis. The aim of our study was to identify potential risk factors for SSIs in a population of patients undergoing TJA.Methods:TJA were prospectively recruited at Casa di Cura Santa Maria Maddalena from February 2019 to April 2020. Age, sex, major comorbidities, American Society of Anesthesiologists (ASA) class, length of surgery, type of surgical suture, total hospital length of stay, and clinical laboratory data were collected. The study population was then divided into two groups: Group A, normal postoperative course, and Group B, patients who developed SSI at follow-up (17-25 days).Results:25/760 (3.3%) patients developed SSIs at follow-up. Clinical and demographic parameters were not different between the two groups. Total leucocyte and neutrophil values at discharge resulted to be significatively higher in Group B compared to Group A (p = 0.025 and p = 0.016, respectively). Values of 7860/μL for total leucocyte and 5185/μL for neutrophil count at discharge significantly predicted the future development of SSI (AUC 0.623 and AUC 0.641, respectively; p < 0.05) independently from confounding factors (total leukocytes: O.R. = 3, 69 [95% C.I. 1,63-8,32]; neutrophils: O.R. = 3, 98 [95% C.I. 1,76-8,97]). Deep SSIs has been diagnosed significantly before superficial SSIs (p = 0,008), with a median advance of 9 days.Conclusion:Total leukocytes and neutrophils at discharge seem useful to identify a population at risk for the development of septic inflammation at the surgical site following TJA. Further studies with larger populations are needed to develop a predictive SSIs risk score that should include those variables.