Journal of Functional Biomaterials

Biopolymer hydrogels have become an important group of biomaterials in experimental and clinical use. However, unlike metallic or mineral materials, they are quite sensitive to sterilization. The aim of this study was to compare the effects of gamma irradiation and supercritical carbon dioxide (scCO₂) treatment on the physicochemical properties of different hyaluronan (HA)- and/or gelatin (GEL)-based hydrogels and the cellular response of human bone marrow-derived mesenchymal stem cells (hBMSC). Hydrogels were photo-polymerized from methacrylated HA, methacrylated GEL, or a mixture of GEL/HA. The composition and sterilization methods altered the dissolution behavior of the biopolymeric hydrogels. There were no significant differences in methacrylated GEL release but increased methacrylated HA degradation of gamma-irradiated samples. Pore size/form remained unchanged, while gamma irradiation decreased the elastic modulus from about 29 kPa to 19 kPa compared to aseptic samples. HBMSC proliferated and increased alkaline phosphatase activity (ALP) particularly in aseptic and gamma-irradiated methacrylated GEL/HA hydrogels alike, while scCO₂ treatment had a negative effect on both proliferation and osteogenic differentiation. Thus, gamma-irradiated methacrylated GEL/HA hydrogels are a promising base for multi-component bone substitute materials. Full article

The reconstruction of blood vessels plays a critical role in the tissue regeneration process. However, existing wound dressings in tissue engineering face challenges due to inadequate revascularization induction and a lack of vascular structure. In this study, we report the modification of mesoporous silica nanospheres (MSNs) with liquid crystal (LC) to enhance bioactivity and biocompatibility in vitro. This LC modification facilitated crucial cellular processes such as the proliferation, migration, spreading, and expression of angiogenesis−related genes and proteins in human umbilical vein endothelial cells (HUVECs). Furthermore, we incorporated LC−modified MSN within a hydrogel matrix to create a multifunctional dressing that combines the biological benefits of LC−MSN with the mechanical advantages of a hydrogel. Upon application to full−thickness wounds, these composite hydrogels exhibited accelerated healing, evidenced by enhanced granulation tissue formation, increased collagen deposition, and improved vascular development. Our findings suggest that the LC−MSN hydrogel formulation holds significant promise for the repair and regeneration of soft tissues. Full article

Catalytically active nanomaterials, in particular, nanozymes, are promising candidates for applications in biosensors due to their excellent catalytic activity, stability and cost-effective preparation. Nanozymes with peroxidase-like activities are prospective candidates for applications in biosensors. The purpose of the current work is to develop cholesterol oxidase-based amperometric bionanosensors using novel nanocomposites as peroxidase (HRP) mimetics. To select the most electroactive chemosensor on hydrogen peroxide, a wide range of nanomaterials were synthesized and characterized using cyclic voltammetry (CV) and chronoamperometry. Pt NPs were deposited on the surface of a glassy carbon electrode (GCE) in order to improve the conductivity and sensitivity of the nanocomposites. The most HRP-like active bi-metallic CuFe nanoparticles (nCuFe) were placed on a previously nano-platinized electrode, followed by conjugation of cholesterol oxidase (ChOx) in a cross-linking film formed by cysteamine and glutaraldehyde. The constructed nanostructured bioelectrode ChOx/nCuFe/nPt/GCE was characterized by CV and chronoamperometry in the presence of cholesterol. The bionanosensor (ChOx/nCuFe/nPt/GCE) shows a high sensitivity (3960 A·M⁻¹·m⁻²) for cholesterol, a wide linear range (2–50 µM) and good storage stability at a low working potential (−0.25 V vs. Ag/AgCl/3 M KCl). The constructed bionanosensor was tested on a real serum sample. A detailed comparative analysis of the bioanalytical characteristics of the developed cholesterol bionanosensor and the known analogs is presented. Full article

Calcium silicate-based cements are used in a variety of clinical conditions affecting the pulp tissue, relying on their inductive effect on tissue mineralization. This work aimed to evaluate the biological response of calcium silicate-based cements with distinct properties—the fast-setting Biodentine™ and TotalFill^® BC RRM™ Fast Putty, and the classical slow-setting ProRoot^® MTA, in an ex vivo model of bone development. Briefly, eleven-day-old embryonic chick femurs were cultured for 10 days in organotypic conditions, being exposed to the set cements’ eluates and, at the end of the culture period, evaluated for osteogenesis/bone formation by combining microtomographic analysis and histological histomorphometric assessment. ProRoot^® MTA and TotalFill^® extracts presented similar levels of calcium ions, although significantly lower than those released from Biodentine^TM. All extracts increased the osteogenesis/tissue mineralization, assayed by microtomographic (BV/TV) and histomorphometric (% of mineralized area; % of total collagen area, and % of mature collagen area) indexes, although displaying distinct dose-dependent patterns and quantitative values. The fast-setting cements displayed better performance than that of ProRoot^® MTA, with Biodentine^TM presenting the best performance, within the assayed experimental model. Full article

Hydrogels show promise in cartilage tissue engineering (CTE) by supporting chondrocytes and maintaining their phenotype and extracellular matrix (ECM) production. Under prolonged mechanical forces, however, hydrogels can be structurally unstable, leading to cell and ECM loss. Furthermore, long periods of mechanical loading might alter the production of cartilage ECM molecules, including glycosaminoglycans (GAGs) and collagen type 2 (Col2), specifically with the negative effect of stimulating fibrocartilage, typified by collagen type 1 (Col1) secretion. Reinforcing hydrogels with 3D-printed Polycaprolactone (PCL) structures offer a solution to enhance the structural integrity and mechanical response of impregnated chondrocytes. This study aimed to assess the impact of compression duration and PCL reinforcement on the performance of chondrocytes impregnated with hydrogel. Results showed that shorter loading periods did not significantly affect cell numbers and ECM production in 3D-bioprinted hydrogels, but longer periods tended to reduce cell numbers and ECM compared to unloaded conditions. PCL reinforcement enhanced cell numbers under mechanical compression compared to unreinforced hydrogels. However, the reinforced constructs seemed to produce more fibrocartilage-like, Col1-positive ECM. These findings suggest that reinforced hydrogel constructs hold potential for in vivo cartilage regeneration and defect treatment by retaining higher cell numbers and ECM content. To further enhance hyaline cartilage ECM formation, future studies should focus on adjusting the mechanical properties of reinforced constructs and exploring mechanotransduction pathways. Full article

Background: A balloon dilatation catheter is a vital tool in percutaneous transluminal angioplasty. Various factors, including the material used, influence the ability of different types of balloons to navigate through lesions during delivery. Objective: Thus far, numerical simulation studies comparing the impacts of different materials on the trackability of balloon catheters has been limited. This project seeks to unveil the underlying patterns more effectively by utilizing a highly realistic balloon-folding simulation method to compare the trackability of balloons made from different materials. Methods: Two materials, nylon-12 and Pebax, were examined for their insertion forces via a bench test and a numerical simulation. The simulation built a model identical to the bench test’s groove and simulated the balloon’s folding process prior to insertion to better replicate the experimental conditions. Results: In the bench test, nylon-12 demonstrated the highest insertion force, peaking at 0.866 N, significantly outstripping the 0.156 N force exhibited by the Pebax balloon. In the simulation, nylon-12 experienced a higher level of stress after folding, while Pebax had demonstrated a higher effective strain and surface energy density. In terms of insertion force, nylon-12 was higher than Pebax in specific areas. Conclusion: nylon-12 exerts greater pressure on the vessel wall in curved pathways when compared to Pebax. The simulated insertion forces of nylon-12 align with the experimental results. However, when using the same friction coefficient, the difference in insertion forces between the two materials is minimal. The numerical simulation method used in this study can be used for relevant research. This method can assess the performance of balloons made from diverse materials navigating curved paths and can yield more precise and detailed data feedback compared to benchtop experiments. Full article

Background and Objectives: Periodontal disease (PD) is a multifactorial oral disease regularly caused by bacterial biofilms. Silver nanoparticles (AgNP) have offered good antimicrobial activity; moreover, there is no available scientific information related to their antimicrobial effects in biofilms from patients with PD. This study reports the bactericidal activity of AgNP against oral biofilms related to PD. Materials and Methods: AgNP of two average particle sizes were prepared and characterized. Sixty biofilms were collected from patients with (30 subjects) and without PD (30 subjects). Minimal inhibitory concentrations of AgNP were calculated and the distribution of bacterial species was defined by polymerase chain reaction. Results: Well-dispersed sizes of AgNP were obtained (5.4 ± 1.3 and 17.5 ± 3.4 nm) with an adequate electrical stability (−38.2 ± 5.8 and −32.6 ± 5.4 mV, respectively). AgNP showed antimicrobial activities for all oral samples; however, the smaller AgNP had significantly the most increased bactericidal effects (71.7 ± 39.1 µg/mL). The most resistant bacteria were found in biofilms from PD subjects (p < 0.05). P. gingivalis, T. denticola, and T. forsythia were present in all PD biofilms (100%). Conclusions: The AgNP showed efficient bactericidal properties as an alternative therapy for the control or progression of PD. Full article

An arteriovenous fistula (AVF) is the access most recommended by several authors. However, its manufacture and use can cause several problems in the short, medium and long term. The study of fluid dynamics related to the structure of the AVF can provide information necessary for the reduction of these problems and a better quality of life for patients. The present study analyzed pressure variation in a rigid and flexible (thickness variation) model of AVFs manufactured based on patient data. A computed tomography was performed from which the geometry of the AVF was removed. This was treated and adapted to the pulsatile flow bench. Bench tests with simulation of systolic–diastolic pulse showed higher pressure peaks in the rigid AVF followed by the flexible model with 1 mm thickness. The inflection of the pressure values of the flexible AVF in relation to the rigid one was observed, being more expressive in the flexible AVF of 1 mm. The 1 mm flexible AVF presented an average pressure close to the physiological one and a smaller pressure drop, showing that this AVF model presents the best condition among the three to serve as a basis for the development of an AVF substitute. Full article

Polymeric heart valves (PHVs) are a promising and more affordable alternative to mechanical heart valves (MHVs) and bioprosthetic heart valves (BHVs). Materials with good durability and biocompatibility used for PHVs have always been the research focus in the field of prosthetic heart valves for many years, and leaflet thickness is a major design parameter for PHVs. The study aims to discuss the relationship between material properties and valve thickness, provided that the basic functions of PHVs are qualified. The fluid−structure interaction (FSI) approach was employed to obtain a more reliable solution of the effective orifice area (EOA), regurgitant fraction (RF), and stress and strain distribution of the valves with different thicknesses under three materials: Carbothane PC−3585A, xSIBS and SIBS−CNTs. This study demonstrates that the smaller elastic modulus of Carbothane PC−3585A allowed for a thicker valve (>0.3 mm) to be produced, while for materials with an elastic modulus higher than that of xSIBS (2.8 MPa), a thickness less than 0.2 mm would be a good attempt to meet the RF standard. What is more, when the elastic modulus is higher than 23.9 MPa, the thickness of the PHV is recommended to be 0.l–0.15 mm. Reducing the RF is one of the directions of PHV optimization in the future. Reducing the thickness and improving other design parameters are reliable means to reduce the RF for materials with high and low elastic modulus, respectively. Full article

The present study aimed to evaluate the effect of dipyridamole, an indirect adenosine 2A receptors (A_2AR), on the osseointegration of titanium implants in a large, translational pre-clinical model. Sixty tapered, acid-etched titanium implants, treated with four different coatings ((i) Type I Bovine Collagen (control), (ii) 10 μM dipyridamole (DIPY), (iii) 100 μM DIPY, and (iv) 1000 μM DIPY), were inserted in the vertebral bodies of 15 female sheep (weight ~65 kg). Qualitative and quantitative analysis were performed after 3, 6, and 12 weeks in vivo to assess histological features, and percentages of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO). Data was analyzed using a general linear mixed model analysis with time in vivo and coating as fixed factors. Histomorphometric analysis after 3 weeks in vivo revealed higher BIC for DIPY coated implant groups (10 μM (30.42% ± 10.62), 100 μM (36.41% ± 10.62), and 1000 μM (32.46% ± 10.62)) in comparison to the control group (17.99% ± 5.82). Further, significantly higher BAFO was observed for implants augmented with 1000 μM of DIPY (43.84% ± 9.97) compared to the control group (31.89% ± 5.46). At 6 and 12 weeks, no significant differences were observed among groups. Histological analysis evidenced similar osseointegration features and an intramembranous-type healing pattern for all groups. Qualitative observation corroborated the increased presence of woven bone formation in intimate contact with the surface of the implant and within the threads at 3 weeks with increased concentrations of DIPY. Coating the implant surface with dipyridamole yielded a favorable effect with regard to BIC and BAFO at 3 weeks in vivo. These findings suggest a positive effect of DIPY on the early stages of osseointegration. Full article

Guided bone regeneration (GBR) is a common procedure used to rebuild dimensional changes in the alveolar ridge that occur after extraction. In GBR, membranes are used to separate the bone defect from the underlying soft tissue. To overcome the shortcomings of commonly used membranes in GBR, a new resorbable magnesium membrane has been developed. A literature search was performed via MEDLINE, Scopus, Web of Science and PubMed in February 2023 for research on magnesium barrier membranes. Of the 78 records reviewed, 16 studies met the inclusion criteria and were analyzed. In addition, this paper reports two cases where GBR was performed using a magnesium membrane and magnesium fixation system with immediate and delayed implant placement. No adverse reactions to the biomaterials were detected, and the membrane was completely resorbed after healing. The resorbable fixation screws used in both cases held the membranes in place during bone formation and were completely resorbed. Therefore, the pure magnesium membrane and magnesium fixation screws were found to be excellent biomaterials for GBR, which supports the findings of the literature review. Full article

Background: Tissue engineering and cell therapy have been the focus of investigations on how to treat challenging bone defects. This study aimed to produce and characterize a P(VDF-TrFE)/BaTiO₃ scaffold and evaluate the effect of mesenchymal stem cells (MSCs) combined with this scaffold and photobiomodulation (PBM) on bone repair. Methods and results: P(VDF-TrFE)/BaTiO₃ was synthesized using an electrospinning technique and presented physical and chemical properties suitable for bone tissue engineering. This scaffold was implanted in rat calvarial defects (unilateral, 5 mm in diameter) and, 2 weeks post-implantation, MSCs were locally injected into these defects (n = 12/group). Photobiomodulation was then applied immediately, and again 48 and 96 h post-injection. The μCT and histological analyses showed an increment in bone formation, which exhibited a positive correlation with the treatments combined with the scaffold, with MSCs and PBM inducing more bone repair, followed by the scaffold combined with PBM, the scaffold combined with MSCs, and finally the scaffold alone (ANOVA, p ≤ 0.05). Conclusions: The P(VDF-TrFE)/BaTiO₃ scaffold acted synergistically with MSCs and PBM to induce bone repair in rat calvarial defects. These findings emphasize the need to combine a range of techniques to regenerate large bone defects and provide avenues for further investigations on innovative tissue engineering approaches. Full article

Bone defects and infections pose significant challenges for treatment, requiring a comprehensive approach for prevention and treatment. Thus, this study sought to evaluate the efficacy of various bone allografts in the absorption and release of antibiotics. A specially designed high-absorbency, high-surface-area carrier graft composed of human demineralized cortical fibers and granulated cancellous bone (fibrous graft) was compared to different human bone allograft types. The groups tested here were three fibrous grafts with rehydration rates of 2.7, 4, and 8 mL/g (F(2.7), F(4), and F(8)); demineralized bone matrix (DBM); cortical granules; mineralized cancellous bone; and demineralized cancellous bone. The absorption capacity of the bone grafts was assessed after rehydration, the duration of absorption varied from 5 to 30 min, and the elution kinetics of gentamicin were determined over 21 days. Furthermore, antimicrobial activity was assessed using a zone of inhibition (ZOI) test with S. aureus. The fibrous grafts exhibited the greatest tissue matrix absorption capacity, while the mineralized cancellous bone revealed the lowest matrix-bound absorption capacity. For F(2.7) and F(4), a greater elution of gentamicin was observed from 4 h and continuously over the first 3 days when compared to the other grafts. Release kinetics were only marginally affected by the varied incubation times. The enhanced absorption capacity of the fibrous grafts resulted in a prolonged antibiotic release and activity. Therefore, fibrous grafts can serve as suitable carrier grafts, as they are able to retain fluids such as antibiotics at their intended destinations, are easy to handle, and allow for a prolonged antibiotic release. Application of these fibrous grafts can enable surgeons to provide longer courses of antibiotic administration for septic orthopedic indications, thus minimizing infections. Full article

This work proposes a sonochemical biosynthesis of magnetoplasmonic nanostructures of Fe₃O₄ decorated with Au and Ag. The magnetoplasmonic systems, such as Fe₃O₄ and Fe₃O₄-Ag, were characterized structurally and magnetically. The structural characterizations reveal the magnetite structures as the primary phase. Noble metals, such as Au and Ag, are present in the sample, resulting in a structure-decorated type. The magnetic measurements indicate the superparamagnetic behavior of the Fe₃O₄-Ag and Fe₃O₄-Au nanostructures. The characterizations were carried out by X-ray diffraction and scanning electron microscopy. Complementarily, antibacterial and antifungal assays were carried out to evaluate the potential properties and future applications in biomedicine. Full article

The aim of this study was to develop an experimental composite resin with the addition of myristyltrimethylammonium bromide (MYTAB) and α -tricalcium phosphate (α-TCP) as an antibacterial and remineralizing material. Experimental composite resins composed of 75 wt% Bisphenol A-Glycidyl Methacrylate (BisGMA) and 25 wt% Triethylene Glycol Dimethacrylate (TEGDMA) were produced. Some 1 mol% Trimethyl benzoyl-diphenylphosphine oxide (TPO) was used as a photoinitiator, and butylated hydroxytoluene (BTH) was added as a polymerization inhibitor. Silica (1.5 wt%) and barium glass (65 wt%) particles were added as inorganic fillers. For remineralizing and antibacterial effect, α-TCP (10 wt%) and MYTAB (5 wt%) were incorporated into the resin matrix (α-TCP/MYTAB group). A group without the addition of α-TCP/MYTAB was used as a control. Resins were evaluated for their degree of conversion (n = 3) by Fourier Transform Infrared Spectroscopy (FTIR). The flexural strength (n = 5) was assessed based on ISO 4049:2019 requirements. Microhardness was assessed to calculate softening in solvent (n = 3) after ethanol immersion. The mineral deposition (n = 3) was evaluated after immersion in SBF, while cytotoxicity was tested with HaCaT cells (n = 5). Antimicrobial activity (n = 3) was analyzed against S. mutans. The degree of conversion was not influenced by the antibacterial and remineralizing compounds, and all groups reached values > 60%. The α-TCP/MYTAB addition promoted increased softening of polymers after immersion in ethanol and reduced their flexural strength and the viability of cells in vitro. A reduction in S. mutans viability was observed for the α-TCP/MYTAB group in biofilm formation and planktonic bacteria, with an antibacterial effect > 3log₁₀ for the developed materials. Higher intensity of phosphate compounds on the sample’s surface was detected in the α-TCP/MYTAB group. The addition of α-TCP and MYTAB promoted remineralizing and antibacterial effects on the developed resins and may be a strategy for bioactive composites. Full article

This study investigated the influence of incorporating Biosilicate^® on the physico-mechanical and biological properties of glass ionomer cement (GIC). This bioactive glass ceramic (23.75% Na₂O, 23.75% CaO, 48.5% SiO₂, and 4% P₂O₅) was incorporated by weight (5%, 10%, or 15%) into commercially available GICs (Maxxion R and Fuji IX GP). Surface characterization was made by SEM (n = 3), EDS (n = 3), and FTIR (n = 1). The setting and working (S/W time) times (n = 3) and compressive strength (CS) were analyzed (n = 10) according to ISO 9917-1:2007. The ion release (n = 6) was determined and quantified by ICP OES and by UV-Vis for Ca, Na, Al, Si, P, and F. To verify cell cytotoxicity, stem cells from the apical papilla (SCAP) were exposed to eluates (n = 3, at a ratio of 1.8 cm²/mL) and analyzed 24 h post-exposure. Antimicrobial activity against Streptococcus mutans (ATCC 25175, NCTC 10449) was analyzed by direct contact for 2 h (n = 5). The data were submitted for normality and lognormality testing. One-way ANOVA and Tukey’s test were applied for the working and setting time, compressive strength, and ion release data. Data from cytotoxicity and antimicrobial activity were submitted for Kruskal–Wallis’ testing and Dunn’s post hoc test (α = 0.05). Among all experimental groups, only those with 5% (wt) of Biosilicate^® showed better surface quality. Only M5% showed a comparable W/S time to the original material (p = 0.7254 and p = 0.5912). CS was maintained for all Maxxion R groups (p > 0.0001) and declined for Fuji IX experimental groups (p < 0.0001). The Na, Si, P, and F ions released were significantly increased for all Maxxion R and Fuji IX groups (p < 0.0001). Cytotoxicity was increased only for Maxxion R with 5% and 10% of Biosilicate^®. A higher inhibition of S. mutans growth was observed for Maxxion R with 5% of Biosilicate^® (less than 100 CFU/mL), followed by Maxxion R with 10% of Biosilicate^® (p = 0.0053) and Maxxion R without the glass ceramic (p = 0.0093). Maxxion R and Fuji IX presented different behaviors regarding Biosilicate^® incorporation. The impacts on physico-mechanical and biological properties were different depending on the GIC, but therapeutic ion release was increased for both materials. Full article

The utilization of cytosolic protein delivery is a promising approach for treating various diseases by replacing dysfunctional proteins. Despite the development of various nanoparticle-based intracellular protein delivery methods, the complicated chemical synthesis of the vector, loading efficiency and endosomal escape efficiency of proteins remain a great challenge. Recently, 9-fluorenylmethyloxycarbonyl (Fmoc)-modified amino acid derivatives have been used to self-assemble into supramolecular nanomaterials for drug delivery. However, the instability of the Fmoc group in aqueous medium restricts its application. To address this issue, the Fmoc ligand neighboring arginine was substituted for dibenzocyclooctyne (DBCO) with a similar structure to Fmoc to obtain stable DBCO-functionalized L-arginine derivative (DR). Azide-modified triethylamine (crosslinker C) was combined with DR to construct self-assembled DRC via a click chemical reaction for delivering various proteins, such as BSA and saporin (SA), into the cytosol of cells. The hyaluronic-acid-coated DRC/SA was able to not only shield the cationic toxicity, but also enhance the intracellular delivery efficiency of proteins by targeting CD44 overexpression on the cell membrane. The DRC/SA/HA exhibited higher growth inhibition efficiency and lower IC₅₀ compared to DRC/SA toward various cancer cell lines. In conclusion, DBCO-functionalized L-arginine derivative represents an excellent potential vector for protein-based cancer therapy. Full article

Background: In the last few decades, the development of multidrug-resistant (MDR) microbes has accelerated alarmingly and resulted in significant health issues. Morbidity and mortality have increased along with the prevalence of infections caused by MDR bacteria, making the need to solve these problems an urgent and unmet challenge. Therefore, the current investigation aimed to evaluate the activity of linseed extract against Methicillin-resistant Staphylococcus aureus (MRSA) as an isolate from diabetic foot infection. In addition, antioxidant and anti-inflammatory biological activities of linseed extract were evaluated. Result: HPLC analysis indicated the presence of 1932.20 µg/mL, 284.31 µg/mL, 155.10 µg/mL, and 120.86 µg/mL of chlorogenic acid, methyl gallate, gallic acid, and ellagic acid, respectively, in the linseed extract. Rutin, caffeic acid, coumaric acid, and vanillin were also detected in the extract of linseed. Linseed extract inhibited MRSA (35.67 mm inhibition zone) compared to the inhibition zone (29.33 mm) caused by ciprofloxacin. Standards of chlorogenic acid, ellagic acid, methyl gallate, rutin, gallic acid, caffeic acid, catechin, and coumaric acid compounds reflected different inhibition zones against MRSA when tested individually, but less than the inhibitory action of crude extract. A lower MIC value, of 15.41 µg/mL, was observed using linseed extract than the MIC 31.17 µg/mL of the ciprofloxacin. The MBC/MIC index indicated the bactericidal properties of linseed extract. The inhibition % of MRSA biofilm was 83.98, 90.80, and 95.58%, using 25%, 50%, and 75%, respectively, of the MBC of linseed extract. A promising antioxidant activity of linseed extract was recorded, with an IC₅₀ value of 20.8 µg/mL. Anti-diabetic activity of linseed extract, expressed by glucosidase inhibition, showed an IC₅₀ of 177.75 µg/mL. Anti-hemolysis activity of linseed extract was documented at 90.1, 91.5, and 93.7% at 600, 800, and 1000 µg/mL, respectively. Anti-hemolysis activity of the chemical drug indomethacin, on the other hand, was measured at 94.6, 96.2, and 98.6% at 600, 800, and 1000 µg/mL, respectively. The interaction of the main detected compound in linseed extract (chlorogenic acid) with the crystal structure of the 4G6D protein of S. aureus was investigated via the molecular docking (MD) mode to determine the greatest binding approach that interacted most energetically with the binding locations. MD showed that chlorogenic acid was an appropriate inhibitor for S. aureus via inhibition of its 4HI0 protein. The MD interaction resulted in a low energy score (−6.26841 Kcal/mol) with specified residues (PRO 38, LEU 3, LYS 195, and LYS 2), indicating its essential role in the repression of S. aureus growth. Conclusion: Altogether, these findings clearly revealed the great potential of the in vitro biological activity of linseed extract as a safe source for combatting multidrug-resistant S. aureus. In addition, linseed extract provides health-promoting antioxidant, anti-diabetic, and anti-inflammatory phytoconstituents. Clinical reports are required to authenticate the role of linseed extract in the treatment of a variety of ailments and prevent the development of complications associated with diabetes mellitus, particularly type 2. Full article

Exosomes have been proven to play a positive role in tendon and tendon–bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes in tendon and tendon–bone healing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic and comprehensive review of the literature was performed on 21 January 2023. The electronic databases searched included Medline (through PubMed), Web of Science, Embase, Scopus, Cochrane Library and Ovid. In the end, a total of 1794 articles were systematically reviewed. Furthermore, a “snowball” search was also carried out. Finally, forty-six studies were included for analysis, with the total sample size being 1481 rats, 416 mice, 330 rabbits, 48 dogs, and 12 sheep. In these studies, exosomes promoted tendon and tendon–bone healing and displayed improved histological, biomechanical and morphological outcomes. Some studies also suggested the mechanism of exosomes in promoting tendon and tendon–bone healing, mainly through the following aspects: (1) suppressing inflammatory response and regulating macrophage polarization; (2) regulating gene expression, reshaping cell microenvironment and reconstructing extracellular matrix; (3) promoting angiogenesis. The risk of bias in the included studies was low on the whole. This systematic review provides evidence of the positive effect of exosomes on tendon and tendon–bone healing in preclinical studies. The unclear-to-low risk of bias highlights the significance of standardization of outcome reporting. It should be noted that the most suitable source, isolation methods, concentration and administration frequency of exosomes are still unknown. Additionally, few studies have used large animals as subjects. Further studies may be required on comparing the safety and efficacy of different treatment parameters in large animal models, which would be conducive to the design of clinical trials. Full article