Regulation of osteogenesis and angiogenesis by cobalt, manganese and strontium doped apatitic materials for functional bone tissue regeneration.

Strontium, cobalt, and manganese ions are present in the composition of bone and useful for bone metabolism, even when combined with calcium phosphate in the composition of biomaterials. Herein we explored the possibility to include these ions in the composition of apatitic materials prepared through the cementitious reaction between ion-substituted calcium phosphate dibasic dihydrate, CaHPO4·2H2O (DCPD) and tetracalcium phosphate, Ca4(PO4)2O (TTCP). The results of the chemical, structural, morphological and mechanical characterization indicate that cobalt and manganese exhibit a greater delaying effect than strontium (about 15 at.%) on the cementitious reaction, even though they are present in smaller amounts within the materials (about 0.8 and 4.5 at.%, respectively). Furthermore, the presence of the foreign ions in the apatitic materials leads to a slight reduction of porosity and to enhancement of compressive strength. The results of biological tests show that the presence of strontium and manganese, as well as calcium, in the apatitic materials cultured in direct contact with human mesenchymal stem cells (hMSCs) stimulates their viability and activity. In contrast, the apatitic material containing cobalt exhibits a lower metabolic activity. All the materials have a positive effect on the expression of Vascular Endothelial Growth Factor (VEGF) and Von Willebrand Factor (vWF). Moreover, the apatitic material containing strontium induces the most significant reduction in the differentiation of preosteoclasts into osteoclasts, demonstrating not only osteogenic and angiogenic properties, but also ability to regulate bone resorption.

Regeneration of Osteochondral Lesion of the Talus with Retrograde Drilling Technique: An In Vitro Pilot Study.

Background: Retrograde Drilling (RD) is a surgical technique employed for osteochondral lesions of the talus (OCLTs) to reach the subchondral bone lesion from behind, thus preserving cartilage integrity. The aim of the present pilot study was to set up an in vitro model of OCLTs to evaluate the regenerative potential of biological approaches that could be associated with the RD technique. Methods: For this purpose, an OCLT was created in human osteochondral specimens, to try to mimic the RD technique, and to compare the regenerative potential of two biological treatments. For this purpose, three groups of treatments were performed in vitro: (1) no treatment (empty defect); (2) autologous bone graft (ABG); (3) hyaluronic membrane enriched with autologous bone marrow cells. Tissue viability; production of Collagen I and II, Vascular Endothelial Growth Factor, and Aggrecan; and histological and microCT evaluations were performed after 30 days of culture in normal culture conditions. Results: It was observed that Group 3 showed the highest viability, and Group 2 showed the highest protein production. From a histological and microtomographic point of view, it was possible to appreciate the structure of the morcellized bone with which the defect of Group 2 was filled, while it was not yet possible to observe the deposition of mineralized tissue in Group 3. Conclusions: To conclude, this pilot study shows the feasibility of an alternative in vitro model to evaluate and compare the regenerative potential of two biological scaffolds, trying to mimic the RD technique as much as possible. The tissues remained vital for up to 4 weeks and both ABG and hyaluronic acid-based scaffolds stimulated the release of proteins linked to regenerative processes in comparison to the empty defect group.

An Advanced Human Bone Tissue Culture Model for the Assessment of Implant Osteointegration In Vitro.

In the field of biomaterials for prosthetic reconstructive surgery, there is the lack of advanced innovative methods to investigate the potentialities of smart biomaterials before in vivo tests. Despite the complex osteointegration process being difficult to recreate in vitro, this study proposes an advanced in vitro tissue culture model of osteointegration using human bone. Cubic samples of trabecular bone were harvested, as waste material, from hip arthroplasty; inner cylindrical defects were created and assigned to the following groups: (1) empty defects (CTRneg); (2) defects implanted with a cytotoxic copper pin (CTRpos); (3) defects implanted with standard titanium pins (Ti). Tissues were dynamically cultured in mini rotating bioreactors and assessed weekly for viability and sterility. After 8 weeks, immunoenzymatic, microtomographic, histological, and histomorphometric analyses were performed. The model was able to simulate the effects of implantation of the materials, showing a drop in viability in CTR+, while Ti appears to have a trophic effect on bone. MicroCT and a histological analysis supported the results, with signs of matrix and bone deposition at the Ti implant site. Data suggest the reliability of the tested model in recreating the osteointegration process in vitro with the aim of reducing and refining in vivo preclinical models.

In vivo validation of highly customized cranial Ti-6AL-4V ELI prostheses fabricated through incremental forming and superplastic forming: an ovine model study.

Cranial reconstructions are essential for restoring both function and aesthetics in patients with craniofacial deformities or traumatic injuries. Titanium prostheses have gained popularity due to their biocompatibility, strength, and corrosion resistance. The use of Superplastic Forming (SPF) and Single Point Incremental Forming (SPIF) techniques to create titanium prostheses, specifically designed for cranial reconstructions was investigated in an ovine model through microtomographic and histomorphometric analyses. The results obtained from the explanted specimens revealed significant variations in bone volume, trabecular thickness, spacing, and number across different regions of interest (VOIs or ROIs). Those regions next to the center of the cranial defect exhibited the most immature bone, characterized by higher porosity, decreased trabecular thickness, and wider trabecular spacing. Dynamic histomorphometry demonstrated differences in the mineralizing surface to bone surface ratio (MS/BS) and mineral apposition rate (MAR) depending on the timing of fluorochrome administration. A layer of connective tissue separated the prosthesis and the bone tissue. Overall, the study provided validation for the use of cranial prostheses made using SPF and SPIF techniques, offering insights into the processes of bone formation and remodeling in the implanted ovine model.

Ionized jet deposition of silver nanostructured coatings: Assessment of chemico-physical and biological behavior for application in orthopedics.

Infection is one of the main issues connected to implantation of biomedical devices and represents a very difficult issue to tackle, for clinicians and for patients. This study aimed at tackling infection through antibacterial nanostructured silver coatings manufactured by Ionized Jet Deposition (IJD) for application as new and advanced coating systems for medical devices. Films composition and morphology depending on deposition parameters were investigated and their performances evaluated by correlating these properties with the antibacterial and antibiofilm efficacy of the coatings, against Escherichia coli and Staphylococcus aureus strains and with their cytotoxicity towards human cell line fibroblasts. The biocompatibility of the coatings, the nanotoxicity, and the safety of the proposed approach were evaluated, for the first time, in vitro and in vivo by rat subcutaneous implant models. Different deposition times, corresponding to different thicknesses, were selected and compared. All silver coatings exhibited a highly homogeneous surface composed of nanosized spherical aggregates. All coatings having a thickness of 50 nm and above showed high antibacterial efficacy, while none of the tested options caused cytotoxicity when tested in vitro. Indeed, silver films impacted on bacterial strains viability and capability to adhere to the substrate, in a thickness-dependent manner. The nanostructure obtained by IJD permitted to mitigate the toxicity of silver, conferring strong antibacterial and anti-adhesive features, without affecting the coatings biocompatibility. At the explant, the coatings were still present although they showed signs of progressive dissolution, compatible with the release of silver, but no cracking, delamination or in vivo toxicity was observed.

Histological and histomorphometric analysis of bone tissue using customized titanium meshes with or without resorbable membranes: A randomized clinical trial.

OBJECTIVES: To date, no clinical studies have investigated the effect of using resorbable collagen membrane in conjunction with customized titanium mesh to promote bone formation in guided bone regeneration. Therefore, a non-inferiority analysis (one-sided 95% CI approach) was designed to compare the augmented bone gained using meshes with and without collagen membranes, through histological and histomorphometric investigations. MATERIALS AND METHODS: Thirty patients undergoing bone augmentation procedures at both maxillary and mandible sites were randomly treated with customized titanium meshes alone (M-, n = 15) or covered with resorbable membrane (M+, n = 15), in both cases filled with autogenous bone and xenograft. After 6 months of healing, bone tissue biopsies were taken from the augmented region. The bone tissue (B.Ar), grafting material (G.Ar), and non-mineralized tissue (NMT.Ar) areas were quantified through histomorphometric analysis, as were the osteoid area (O.Ar) and its width. RESULTS: Collagen membrane did not appear to significantly influence the investigated parameters: B.Ar, G.Ar, NMT.Ar, and O.Ar were similar between Group M- (34.3%, 11.5%, 54.1%, 1.95 µm2 , respectively) and Group M+ (35.3%, 14.6%, 50.2%, and 1.75 µm2 , respectively). Considering the overall population, significantly higher rates of newly formed bone were obtained in mandibular sites, while non-mineralized and dense connective tissue rates were higher in the maxilla (p < .05). CONCLUSIONS: The application of collagen membrane over titanium mesh did not lead to significant results. Bone formation appeared significantly different in the maxilla compared with the mandible. Additional studies are required to further investigate the issues observed.

A Systematic Review of the Retrograde Drilling Approach for Osteochondral Lesion of the Talus: Questioning Surgical Approaches, Outcome Evaluation and Gender-Related Differences.

BACKGROUND: Retrograde drilling (RD) is a minimally invasive surgical procedure mainly used for non-displaced osteochondral lesions (OCL) of the talus, dealing with subchondral necrotic sclerotic lesions or subchondral cysts without inducing iatrogenic articular cartilage injury, allowing the revascularization of the subchondral bone and new bone formation. METHODS: This systematic review collected and analyzed the clinical studies of the last 10 years of literature, focusing not only on the clinical results but also on patients' related factors (gender, BMI, age and complications). RESULTS: Sixteen clinical studies were retrieved, and differences in the type of study, follow-up, number and age of patients, lesion type, dimensions, grades and comparison groups were observed, making it difficult to draw conclusions. Nevertheless, lesions on which RD showed the best results were those of I-III grades and not exceeding 150 mm2 in size, showing overall positive results, a good rate of patient satisfaction, improvements in clinical scores, pain reduction and return to daily activities and sports. CONCLUSIONS: There are still few studies dealing with the issue of post-surgical complications and gender-related responses. Further clinical or preclinical studies are thus mandatory to underline the success of this technique, also in light of gender differences.

RNA Extraction from Cartilage: Issues, Methods, Tips.

The increase in degenerative diseases involving articular cartilage has pushed research to focus on their pathogenesis and treatment, exploiting increasingly complex techniques. Gene expression analyses from tissue are representative of the in vivo situation, but the protocols to be applied to obtain a reliable analysis are not completely cleared through customs. Thus, RNA extraction from fresh samples and specifically from musculoskeletal tissue such as cartilage is still a challenging issue. The aim of the review is to provide an overview of the techniques described in the literature for RNA extraction, highlighting limits and possibilities. The research retrieved 65 papers suitable for the purposes. The results highlighted the great difficulty in comparing the different studies, both for the sources of tissue used and for the techniques employed, as well as the details about protocols. Few papers compared different RNA extraction methods or homogenization techniques; the case study reported by authors about RNA extraction from sheep cartilage has not found an analog in the literature, confirming the existence of a relevant blank on studies about RNA extraction from cartilage tissue. However, the state of the art depicted can be used as a starting point to improve and expand studies on this topic.

Bone Regeneration Guided by a Magnetized Scaffold in an Ovine Defect Model.

The reconstruction of large segmental defects still represents a critical issue in the orthopedic field. The use of functionalized scaffolds able to create a magnetic environment is a fascinating option to guide the onset of regenerative processes. In the present study, a porous hydroxyapatite scaffold, incorporating superparamagnetic Fe3O4 nanoparticles (MNPs), was implanted in a critical bone defect realized in sheep metatarsus. Superparamagnetic nanoparticles functionalized with hyperbranched poly(epsilon-Lysine) peptides and physically complexed with vascular endothelial growth factor (VEGF) where injected in situ to penetrate the magnetic scaffold. The scaffold was fixed with cylindrical permanent NdFeB magnets implanted proximally, and the magnetic forces generated by the magnets enabled the capture of the injected nanoparticles forming a VEGF gradient in its porosity. After 16 weeks, histomorphometric measurements were performed to quantify bone growth and bone-to-implant contact, while the mechanical properties of regenerated bone via an atomic force microscopy (AFM) analysis were investigated. The results showed increased bone regeneration at the magnetized interface; this regeneration was higher in the VEGF-MNP-treated group, while the nanomechanical behavior of the tissue was similar to the pattern of the magnetic field distribution. This new approach provides insights into the ability of magnetic technologies to stimulate bone formation, improving bone/scaffold interaction.

Vitamin D and Platelets: A Menacing Duo in COVID-19 and Potential Relation to Bone Remodeling.

Global data correlate severe vitamin D deficiency with COVID-19-associated coagulopathy, further suggesting the presence of a hypercoagulable state in severe COVID-19 patients, which could promote thrombosis in the lungs and in other organs. The feedback loop between COVID-19-associated coagulopathy and vitamin D also involves platelets (PLTs), since vitamin D deficiency stimulates PLT activation and aggregation and increases fibrinolysis and thrombosis. Vitamin D and PLTs share and play specific roles not only in coagulation and thrombosis but also during inflammation, endothelial dysfunction, and immune response. Additionally, another 'fil rouge' between vitamin D and PLTs is represented by their role in mineral metabolism and bone health, since vitamin D deficiency, low PLT count, and altered PLT-related parameters are linked to abnormal bone remodeling in certain pathological conditions, such as osteoporosis (OP). Hence, it is possible to speculate that severe COVID-19 patients are characterized by the presence of several predisposing factors to bone fragility and OP that may be monitored to avoid potential complications. Here, we hypothesize different pervasive actions of vitamin D and PLT association in COVID-19, also allowing for potential preliminary information on bone health status during COVID-19 infection.

Skin adhesion to the percutaneous component of direct bone anchored systems: systematic review on preclinical approaches and biomaterials.

Nowadays, direct bone anchored systems are an increasingly adopted approach in the therapeutic landscape for amputee patients. However, the percutaneous nature of these devices poses a major challenge to obtain a stable and lasting proper adhesion between the implant surface and the skin. A systematic review was carried out in three databases (PubMed, Scopus, Web of Science) to provide an overview of the innovative strategies tested with preclinical models (in vitro and in vivo) in the last ten years to improve the skin adhesion of direct bone anchored systems. Fifty five articles were selected after screening, also employing PECO question and inclusion criteria. A modified Cochrane RoB 2.0 tool for the in vitro studies and the SYRCLE tool for in in vivo studies were used to assess the risk of bias. The evidence collected suggests that the implementation of porous percutaneous structures could be one of the most favorable approach to improve proper skin adhesion, especially in association with bioactive coatings, as hydroxyapatite, and exploiting the field of nanostructure. Some issues still remain open as (a) the identification and characterization of the best material/coating association able to limit the shear stresses at the interface and (b) the role of keratinocyte turnover on the skin/biomaterial adhesion and integration processes.

Determination of the Spatial Anisotropy of the Surface MicroStructures of Different Implant Materials: An Atomic Force Microscopy Study.

Many biomaterials' surfaces exhibit directional properties, i.e., possess spatial anisotropy on a range of spatial scales spanning from the domain of the naked eye to the sub-micrometer level. Spatial anisotropy of surface can influence the mechanical, physicochemical, and morphological characteristics of the biomaterial, thus affecting its functional behavior in relation, for example, to the host tissue response in regenerative processes, or to the efficacy of spatially organized surface patterns in avoiding bacterial attachment. Despite the importance of the availability of quantitative data, a comprehensive characterization of anisotropic topographies is generally a hard task due to the proliferation of parameters and inherent formal complications. This fact has led so far to excessive simplification that has often prevented researchers from having comparable results. In an attempt to overcome these issues, in this work a systematic and multiscale approach to spatial anisotropy is adopted, based on the determination of only two statistical parameters of surface, namely the texture aspect ratio Str and the roughness exponent H, extracted from atomic force microscopy images of the surface. The validity on this approach is tested on four commercially available implant materials, namely titanium alloy, polyethylene, polyetheretherketone and polyurethane, characterized by textured surfaces obtained after different machining. It is found that the "two parameters" approach is effective in describing the anisotropy changes on surfaces with complex morphology, providing a simple quantitative route for characterization and design of natural and artificial textured surfaces at spatial scales relevant to a wide range of bio-oriented applications.

Titanium implant coating based on dopamine-functionalized sulphated hyaluronic acid: in vivo assessment of biocompatibility and antibacterial efficacy.

The number of total knee and/or hip replacements are expected to exceed 5 million a year by 2030; the incidence of biofilm-associated complications can vary from 1% in primary implants to 5.6% in case of revision. The purpose of this study was to test the ability of sHA-DA, a partially sulphated hyaluronic acid (sHA) functionalized with a dopamine (DA) moiety, to prevent acute bacterial growth in an in vivo model of an intra-operatively highly contaminated implant. Previously, in vitro studies showed that the DA moiety guarantees good performance as binding agent for titanium surface adhesion, while the negatively charged sHA has both a high efficiency in electrostatic binding of positively charged antibiotics, and bone regenerative effects. The in vitro testing also highlighted the effectiveness of the sHA-DA system in inhibiting bacterial spreading through a sustained release of the antibiotic payload from the implant coating. In this study the chemical stability of the sHA-DA to ß-ray sterilization was demonstrated, based on evaluation by NMR, SEC-TDA Omnisec and HPLC-MS analysis, thus supporting the approach of terminal sterilization of the coated implant with no loss of efficacy. Furthermore, an in vivo study in rabbits was performed according to UNI EN ISO 10993-6 to assess the histocompatibility of titanium nails pre-coated with sHA-DA. The implants, placed in the femoral medullary cavity and harvested after 12 weeks, proved to be histocompatible and to allow bone growth in adhesion to the metal surface. Finally, an in vivo model of bacterial contamination was set up by injecting 1 mL of bacterial suspension containing 104 or 106 CFU of methicillin-resistant Staphylococcus aureus (MRSA) into the femoral medullary cavity of 30 rabbits. Titanium nails either uncoated or pre-coated with sHA-DA and loaded directly by the surgeon with 5% vancomycin were implanted in the surgical site. After 1 week, only the animals treated with pre-coated nails did not show the presence of systemic or local bacterial infection, as confirmed by microbiology and histology (Smeltzer score). Further insights into the animal model setup are crucial, however the results obtained suggest that the system can be effective in preventing the onset of the bacterial infective process.

Anisotropy and inhomogeneity of permeability and fibrous network response in the pars intermedia of the human lateral meniscus.

Within the human tibiofemoral joint, meniscus plays a key role due to its peculiar time-dependent mechanical characteristics, inhomogeneous structure and compositional features. To better understand the pathophysiological mechanisms underlying this essential component, it is mandatory to analyze in depth the relationship between its structure and the function it performs in the joint. Accordingly, the aim of this study was to evaluate the behavior of both solid and fluid phases of human meniscus in response to compressive loads, by integrating mechanical assessment and histological analysis. Cubic specimens were harvested from seven knee lateral menisci, specifically from anterior horn, pars intermedia and posterior horn; unconfined compressive tests were then performed according to three main loading directions (i.e., radial, circumferential and vertical). Fibril modulus, matrix modulus and hydraulic permeability of the tissue were thence estimated through a fibril-network-reinforced biphasic model. Tissue porosity and collagen fibers arrangement were assessed through histology for each region and related to the loading directions adopted during mechanical tests. Regional and strain-dependent constitutive parameters were finally proposed for the human lateral meniscus, suggesting an isotropic behavior of both the horns, and a transversely isotropic response of the pars intermedia. Furthermore, the histological findings supported the evidences highlighted by the compressive tests. Indeed, this study provided novel insights concerning the functional behavior of human menisci by integrating mechanical and histological characterizations and thus highlighting the key role of this component in knee contact mechanics and presenting fundamental information that can be used in the development of tissue-engineered substitutes. STATEMENT OF SIGNIFICANCE: This work presents an integration to the approaches currently used to model the mechanical behavior of the meniscal tissue. This study assessed in detail the regional and directional contributions of both the meniscal solid and fluid phases during compressive response, providing also complementary histological evidence. Within this updated perspective, both knee computational modeling and meniscal tissue engineering can be improved to have an effective impact on the clinical practice.

Blood factors as biomarkers in osteoporosis: points from the COVID-19 era.

The restrictions adopted during the coronavirus disease 2019 (COVID-19) pandemic limiting direct medical consultations and access to healthcare centers reduced the participation of patients with chronic diseases, such as osteoporosis (OP), in screening and monitoring programs. This highlighted the need for new screening diagnostic tools that are clinically effective, but require minimal technical and time commitments, to stratify populations and identify who is more at risk for OP and related complications. This paper provides an overview of the potential use of blood-related factors, such as platelet (PLT)- and monocyte-related factors, as biomarkers able to quickly screen, detect, and monitor OP in both sexes. Such biomarkers might be of key importance not only during the COVID-19 pandemic but also, even more importantly, during periods of better global health stability.

Stromal Vascular Fraction and Amniotic Epithelial Cells: Preclinical and Clinical Relevance in Musculoskeletal Regenerative Medicine.

Musculoskeletal regenerative medicine is mainly based on the use of cell therapy to heal damaged tissues such as bone, cartilage, and tendons. Throughout the years, different cell types have been employed for the treatment of musculoskeletal diseases, in particular, mesenchymal stem cells (MSCs) derived from bone marrow (BMSCs) and adipose tissue (ADSCs). Though the results of these literature studies have been encouraging, there are some limitations, especially on long-term results. Recently, some interest has shifted towards new cell types such as the stromal vascular fraction (SVF) and amniotic endothelial cells (AECs). The aim of the present literature review is to evaluate preclinical and clinical studies that used SVF and AECs for musculoskeletal tissue regeneration. Forty-eight preclinical and clinical studies, performed in the last 10 years, were identified. Both SVF and AECs, injected or implanted with or without scaffolds, were shown to be valid alternatives, and in some ways superior, to ADSCs and BMSCs, being able to differentiate towards osteogenic, chondrogenic, and tenogenic lineages, and to promote cell and tissue regenerative potential. The use of SVF and AECs could represent a new regenerative treatment in several musculoskeletal pathologies, solving the problem of cell expansion in vitro.

Osseointegration of additive manufacturing Ti-6Al-4V and Co-Cr-Mo alloys, with and without surface functionalization with hydroxyapatite and type I collagen.

The introduction of additive manufacturing (AM) technologies has profoundly revolutionized the implant manufacturing industry, with a particularly significant impact on the field of orthopedics. Electron Beam Melting (EBM) and Direct Metal Laser Sintering (DMLS) represents AM fabrication techniques with a pivotal role in the realization of complex and innovative structure starting from virtual 3D model data. In this study, Ti-6Al-4V and Co-Cr-Mo materials, developed by EBM (Ti-POR) and DMLS (Co-POR) techniques, respectively, with hydroxyapatite (Ti-POR + HA; Co-POR + HA) and type I collagen (Ti-POR-COLL; Co-POR-COLL) coatings, were implanted into lateral femoral condyles of rabbits. Osseointegration process was investigated by histological, histomorphometrical and microhardness evaluations at 4 and 12 weeks after implantation. Both Ti-6Al-4V and Co-Cr-Mo implants, with or without HA and COLL coatings, demonstrated good biocompatibility. As expected, HA coating hastened bone-to-implant contact (BIC) process, while collagen did not significantly improved the osseointegration process in comparison to controls. Regarding newly trabecular bone formation (B.Ar/T.Ar), Co-POR presented the highest values, significantly different from those of Co-POR-COLL. Over time, an increase of BIC parameter and a decrease of B.Ar/T.Ar were detected. Higher mineral apposition rate was observed for Ti-POR and Co-POR in comparison to Ti-POR-COLL and Co-POR-COLL, respectively, at 12 weeks. The same behavior was found for bone formation rate between Co-POR and Co-POR-COLL at 12 weeks. In conclusion, the AM materials guarantee a good osseointegration and provide a suitable environment for bone regeneration with the peculiarity of allowing personalized and patient-specific needs customization to further improve the long-term clinical outcomes.

Body Localization of ACE-2: On the Trail of the Keyhole of SARS-CoV-2.

The explosion of the new coronavirus (SARS-CoV-2) pandemic has brought the role of the angiotensin converting enzyme 2 (ACE2) back into the scientific limelight. Since SARS-CoV-2 must bind the ACE2 for entering the host cells in humans, its expression and body localization are critical to track the potential target organ of this infection and to outline disease progression and clinical outcomes. Here, we mapped the physiological body distribution, expression, and activities of ACE2 and discussed its potential correlations and mutal interactions with the disparate symptoms present in SARS-CoV-2 patients at the level of different organs. We highlighted that despite during SARS-CoV-2 infection ACE2-expressing organs may become direct targets, leading to severe pathological manifestations, and subsequent multiple organ failures, the exact mechanism and the potential interactions through which ACE2 acts in these organs is still heavily debated. Further scientific efforts, also considering a personalized approach aimed to consider specific patient differences in the mutual interactions ACE2-SARS-CoV-2 and the long-term health effects associated with COVID-19 are currently mandatory.

Platelet functions and activities as potential hematologic parameters related to Coronavirus Disease 2019 (Covid-19).

Coronavirus disease 2019 (COVID-19) is a new infectious disease that currently lacks standardized and established laboratory markers to evaluate its severity. In COVID-19 patients, the number of platelets (PLTs) and dynamic changes of PLT-related parameters are currently a concern. The present paper discusses the potential link between PLT parameters and COVID-19. Several studies have identified a link between severe COVID-19 patients and specific coagulation index, in particular, high D-dimer level, prolonged prothrombin time, and low PLT count. These alterations reflect the hypercoagulable state present in severe COVID-19 patients, which could promote microthrombosis in the lungs, as well as in other organs. Further information and more advanced hematological parameters related to PLTs are needed to better estimate this link, also considering COVID-19 patients at different disease stages and stratified in different cohorts based on preexisting co-morbidity, age, and gender. Increasing the understanding of PLT functions in COVID-19 will undoubtedly improve our knowledge on disease pathogenesis, clinical management, and therapeutic options, but could also lead to the development of more precise therapeutic strategies for COVID-19 patients.