Osteosarcoma (OS), the most prevalent primary bone malignancy, continues to attract attention from interdisciplinary researchers due to its therapeutic challenges. In this study, multifunctional 3D-printed coated scaffolds based on lithium-substituted mesoporous bioactive glasses Li-MBGs (Li = 7 wt %) were developed for combined drug delivery, bioactivity, and biocompatibility. Li-MBGs were synthesized and characterized for morphology, mesoporosity, particle size, surface charge, and textural properties using TEM, BET, and zeta potential analyses. The structural and surface features of MBGs and 3D-printed scaffolds were further investigated by XRD, FTIR, and SEM. Doxorubicin (DOX) was incorporated into the Li-MBGs, and its release was evaluated under physiological conditions. In-vitro studies assessed ion release, degradation, swelling, pH stability, and bioactivity. The biological performance of drug-loaded MBGs and coated scaffolds was evaluated through cytotoxicity (MTT assay), cell death mode, and ALP activity in MG-63 osteosarcoma cells. The results demonstrated that the coated scaffolds enhanced mineralization and bioactivity, while DOX release followed pH-dependent, diffusioncontrolled kinetics. Furthermore, DOX-loaded, Li-MBG-coated scaffolds exhibited enhanced anticancer activity by promoting apoptosis (25 %) and necrosis (5 %) in MG-63 cells, whereas unloaded scaffolds maintained good biocompatibility. These findings highlight Li-MBG-based multifunctional scaffolds as promising candidates for osteosarcoma treatment and bone regeneration.
Tissue engineering has emerged as a promising field for patients with bone injuries. It involves using cultured cells, scaffolds, and signals that promote bone growth to regenerate tissues. The purpose of the current study was to fabricate a more strategic method to accelerate the healing process following bone injuries. The electrospinning technique was utilized to create polyvinylidene fluoride/polycaprolactone nanofibrous scaffolds loaded with the antibiotic amoxicillin and incorporating nano-mesoporous zirconia. Scanning electron microscopy (SEM) examined the morphology of the 3D scaffolds. The presence of these nanoparticles within the fibrous scaffolds was found to affect fiber diameters (approximate to 50-550 nm) and their distribution ranges as well. A combination of X-ray diffractometry (XRD) and infrared spectroscopy (FTIR) was utilized in order to investigate the physicochemical characteristics. The in vitro bioactivity of the 3D scaffold was evaluated in simulated body fluid (SBF) and The EDX analysis of amoxicillin loaded nanofiberous scaffold (PVDF/PCL-MZNs-AMOX) revealed Ca/P ratio = 1.69, demonstrating the development of carbonated hydroxyapatite (CHA), which is similar to actual bone apatite, Examining the elution profile of the amoxicillin drug from the nanofibrous samples implies that both samples were able to deliver the drug successfully for time period of up to 10 days in vitro in phosphate buffered saline (PBS) at two different pHs 7.4 and 5.At pH 7.4 more than 83 % of the drug was released while at pH 5 it was decreased to 65 %. Thus, ZrO2-loaded nanofibers have the potential to serve as a regulated amoxicillin delivery system. Promising microstructure and physicochemical features, demonstrated by the 3D scaffolds that were suitable for optimal and acceleration of bone regeneration, emphasized how amoxicillin affected the rates of healing and cell growth. Successful bone healing of the defected rabbit femur after 3 weeks of treatment with nanofibrous scaffolds was obtained. The presence of nanoparticles combined with the amoxicillin drug within the nanofibrous scaffolds demonstrated great enhancements for the biomineralization rate (bioactivity) and the bone-bonding ability of the obtained 3D scaffolds. Therefore, the prepared 3D scaffolds loaded with amoxicillin are highly recommended as cheap alternatives for bone repair.
Chronic infected wounds with multi-drug resistant pathogens present severe therapeutic challenges, often leading to prolonged morbidity and impaired healing. To address this, we engineered a multifunctional wound dressing by integrating Voriconazole-loaded silver/zinc MOFs (VOR@Ag/Zn-MOFs) into a hyaluronic acid/polyvinylpyrrolidone (HA/PVP) matrix. The composite was prepared through sequential steps, including preparing a HA/PVP polymer blend via solvent dissolution, synthesizing bimetallic Ag/Zn-MOFs through chemical precipitation, loading VOR into MOF nanocages, and consolidating the composite via chemical crosslinking followed by freeze-drying. Comprehensive physicochemical characterization to confirm MOF stability was implemented through SEM/EDX, confirming uniform nanocage architecture and elemental distribution (Ag/Zn/F), while DLS revealed controlled particle dimensions, and optimal colloidal stability (PDI 0.694; ZP + 39.3 mV). FTIR confirmed structural integrity through preserved polymer peaks (O–H 3400–3200, C = O 1650 cm⁻1), VOR-specific C-F (1400–1200 cm⁻1), and MOF Zn–O bonds (1100–1000/400–600 cm⁻1), verifying non-covalent integration without degradation. XRD further verified the crystalline framework integrity. In-vitro release studies demonstrated sustained biphasic release (44.2
Cerium-doped hydroxyapatite of varying concentrations (0, 3, 5 & 7 %) was electrospun onto a polyamide/ gelatin (Pa-Gel) to form nanofibrous membranes to be used as guided bone regeneration that help in the development of new bone to support and supplement areas of inadequate bone volume surrounding dental implants and other restorative dental operations. Contact angle measurements, biodegradation, bioactivity, ion release, and cell culture assay were used to determine the cerium-doped hydroxyapatite ideal concentration. The results revealed all the fibrous membranes are at the nano-level and the nano particles are well embedded inside the fibers. It was found that the hydroxyapatite doped with cerium improved the physiochemical and biological characteristics when compared to pure hydroxyapatite. Increasing cerium doping percentages lead to a high hydrophilicity (0 degrees) compared to the membrane that contains solely hydroxyapatite (38 degrees). The prepared membranes showed improved degradation rate and mechanical properties. The MTT assay showed that the membranes were non-toxic. Moreover, when compared to the control, the cellular proliferation was observed to be greatly increased by up to 215 % at the optimal concentration, namely Pa-Gel-5 %Ce-HA. Depending on the results, the prepared nanofibrous membranes are very promising for application as a guided bone regeneration membrane.
This work is reported for the preparation and characterization of nano bioactive glass doped with copper and strontium in the system (SiO2-CaO-P2O5-CuO-SrO).Compared to traditional procedures, the Sol-gel approach offers a number of advantages for glass formation, including improved control over size and morphology. At the expense of CaO, CuO and SrO were added to the glass compositions. CuO and SrO were used for their highly antibacterial effects and bioactivity enhancement. To confirm the bioactivity of all the glass samples, scanning electron microscopy (SEM), Brunauer Emmett Teller (BET) surface area measurements, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) were used to assess the morphological and structural characteristics of the produced glasses. The particles that developed on the glass samples' surface during immersion in the simulated body fluid (SBF) were analysed to detect the glasses' bioactivity. The hydroxyapatite (HAp) layer's development was verified by EDX analysis. ICP (Inductively Coupled Plasma) Spectroscopy was used to analyse the ion release in the SBF solution. Additionally, the impact of the antibacterial activity on several types of bacteria (including Gram-positive, Gram-negative, and antifungal bacteria) was examined. Moreover, Ciprofloxacin was used as a model medication to test the drug loading efficiency. The Korsmeyer-Peppas kinetic model and zero order models were used to study the drug release mechanisms. The cytotoxicity of the nano-bioactive glass against human bone osteosarcoma cells (MG-63) and bone marrow stromal cells was also evaluated using the MTT assay.
Treating severe bone deformities and abnormalities continues to be a major clinical hurdle, necessitating the adoption of suitable materials that can actively stimulate bone regeneration. Magnesium phosphate (MP) is a material that has the ability to stimulate the growth of bones. The current study involved the synthesis of mesoporous MP and lanthanum (La)-doped nanopowders using a chemical precipitation approach. The nanopowders were analyzed using several techniques, including XRD, FTIR, HR-TEM, BET, XPS, and FE-SEM. The results confirmed the nanopowders' size of less than 40 nm and the successful incorporation of La3+ ions into the MP structure. The bioactivity of the materials was assessed in vitro using simulated bodily fluid (SBF) at 37°C for a duration of 14 days in a shaker incubator (50 rpm). The SEM showed that a bone-like apatite layer formed quickly on the nanopowders' surface, proving that they have unique bioactive properties. The EDX spectra confirmed the presence of Ca, P, Mg, and La elements after immersion in SBF. The MP nanopowders, both with and without La doping, demonstrated the capacity to stimulate bone formation in a rat femoral bone defect model over a 28-day duration. Radiographic and histological studies showed that the La-doped MP nanopowders greatly improved bone repair and regeneration in comparison to the La-free nanopowders. Finally, the readily producible mesoporous MP nanomaterials, especially those with increased La doping (up to 7 wt%), exhibit significant potential for the restoration of large bone defects. Hence, fabricated nanopowders have immense promise for repairing bone criterion defects.
This review focuses on recent advancements in the effective use of mesoporous bioactive glasses (MBG) in the treatment of bone cancer, focusing on Osteosarcoma (OS). Bone cancers are rare but are associated with significant morbidity and mortality; often, aggressive treatment is required. Conventional treatments such as surgery, radiation, and chemotherapy are often not enough. This is because surgery cannot completely remove the tumor, without creating a critical size which are defects larger than 2 cm that cannot be repaired by physiological mechanisms. As a result, patients often face the additional burden of radiation and chemotherapy. Scientists have been exploring new treatments, including hyperthermia-targeted therapy, polymeric nanoparticles, and stem cell therapy. This could potentially negatively impact healthy tissues and organs. MBG offers a promising alternative to chemotherapeutic agents and ions for disease treatment as it acts as a multifunctional drug delivery system (DDS). In addition, MBG can also be engineered into scaffolds to facilitate local delivery of growth factors and drugs, thus promoting the efficiency of bone healing and restoration. Therefore, the current review highlights various MBG types reported in the past decade and explores potential future paths to enhance their use in bone cancer treatment while also giving insight on the already commercially available BGs that are used in different bone-related disease.
In wound treatment, sustainable and effective dressings are crucial for rapid healing without scarring. Antimicrobial transparent hydrogel dressings were fabricated by grafting chitosan with polyvinyl pyrrolidone and impregnating it with zinc or zinc-silver metal-organic framework nanocages (30-50 nm). Characterization confirmed the hydrogels' excellent physical and chemical integrity. Comprehensive antibacterial, antifungal, and ion-release evaluations validated their efficacy, demonstrating remarkable results. These dressings also promoted a moisture-balanced environment ideal for wound healing. Comprehensive evaluations of these hydrogel dressings' antibacterial, antifungal, and ion-release properties confirmed their efficacy, demonstrating remarkable results. The dressings also promoted a moisture-balanced environment optimal for wound healing. Cytotoxicity tests on skin cells indicated that the hydrogels were safe and enhanced cell proliferation. Notably, CS/ PVP hydrogels with bimetallic nanocages (CS/PVP4) achieved up to 69 % healing within 7 days. This rapid healing occurred due to the reduction of inflammation and IL-1 content in the dermis; the downregulation of MMP9 halted the breakdown of the extracellular matrix (ECM); the upregulation of TGF accelerated cell growth and raised the levels of collagen 1 and -SMA in the ECM. These findings suggest that the developed hydrogel dressings will provide sustainable wound healing, thereby increasing patient satisfaction.
Gold-wollastonite nanocomposites were created by integrating gold nanoparticles with wollastonite, then tested in simulated body fluid and implanted in rat bone defects. Results showed significant bone healing compared to untreated defects.
The current study used the precipitation method to prepare pure calcium hydroxyapatite (HA) and ceriumsubstituted hydroxyapatite (Ce-HA) nanoparticles, where cerium ions were exchanged into the HA structure at different concentrations ranging from 3 to 7 wt%. X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), high resolution transmission electron microscopy (HR-TEM), Fourier transform infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET) surface area measurements, and zeta potential were used to examine the structural characteristics of the nanoparticles. Additionally, the antibacterial and antifungal effects of the produced materials on Gram-positive, Gram-negative, and fungal bacterial species were studied. Nanoparticles with cerium doping showed effective antibacterial and antifungal properties. All samples were tested for bioactivity in simulated body fluid (SBF), and the formation of an apatite layer on their surfaces was highlighted using SEM in conjunction with energy-dispersive X-rays (EDX).Doxorubicin (DOX) release from CeHA nanoparticles and pure HA was tested in phosphate-buffered saline (PBS) for up to 28 days. Both nanoparticles were able to release the drug while still being semi-fully loaded. Similarly, the cytotoxic effect of all produced samples on the MG-63 cell line was evaluated, and all samples showed good cytocompatibility. The cytotoxic effect of doxorubicin-loaded nanoparticles showed promising anticancer activity against bone cancer cells, especially samples with high cerium content. The resulting nanoparticles show excellent promising ability for the delivery of doxorubicin to bone cancer with the capacity for bone regeneration.
Nanoporous membranes (NPMBs) have been the focus of interest of many scientists in the last decade. However, the fouling phenomenon that takes place during the implantation period blocks pores and causes failure in the local implant. In this study, alumina NPMBs were developed using electrochemical anodization through two steps. Furthermore, graphene oxide (GO), free and impregnated with ZIF-8 MOF, was synthesized and loaded in a mixture of PVDF/PVP polymer matrix at different ratios, and was applied to the produced NPMBs using spin-coater. The NPMBs were characterized before and after coating by SEM/EDX, TEM, FTIR, XRD, contact angle and AFM. The antifouling features of the NPMBs were analyzed against two different bacterial species. The prepared alumina NPMBs demonstrated homogeneous porous structures with pore sizes ranging from 36 to 39 nm. The coated layers were proven to possess microporous coatings on the surfaces of the NPMBs. The numbers of released ions (Al and Zn) from the coated NPMBs were below the allowed limits. Bovine serum albumin (BSA) uptake in artificial cerebrospinal fluid (ACSF) was impressively reduced with the presence of coating materials. In addition, the antifouling behavior of the coated NPMBs against the selected strains of bacteria was greatly enhanced compared with the pure alumina NPMBs. Finally, NPMBs’ uncoated and polymer-coated membranes were tested for their ability to deliver donepezil HCl. The results reveal the downregulation of donepezil release, especially from NPMBs coated with PVDF/PVP 0.5GO. It is advised to use the current antifouling materials and techniques to overcome the limitations of the inorganic NPMBs implants.
This work investigates the bioactivity of pure Wollastonite and gold-doped Wollastonite nanohybrids synthesized via a wet chemical technique. Doping with gold nanoparticles at different ratios for Wollastonite, where a dramatic decrease in the respective average particle sizes at the lowest doping ratio of 1.25 wt/v%, then the particle size raised gradually with an increase in the content of gold nanoparticles. In addition, a significant increase in the calculated surface area and the cumulative pore volume upon incorporating gold nanoparticles with the lowest doping ratio of 1.25 wt./v% is associated with a slight decrease in the average pore size. Then, a gradual decrease in the calculated surface area and cumulative pore volume with the increase of doping ratio with gold nanoparticles is associated with an increase in average pore size. The results revealed that after two days of incubation for treated MG-63 cells, the W/Au 5 wt/v% showed the significantly highest alkaline phosphatase (ALP) activity among all other concentrations and the control cells. The ALP activity exceeded four mU/mL. After four days of incubation, the ALP activity in all doping ratios was significantly higher than the control cells, with no significant difference among other groups, but lower than ALP levels after two days of incubation. Also, pure Wollastonite and gold-doped Wollastonite nanohybrids, especially the lowest doping ratio of 1.25 wt/v%, have remarkable efficacy in combating E. coli (Gram-negative), S. aureus (Gram-positive) and Candida albicans. In vitro studies showed that pure Wollastonite and gold-doped Wollastonite nanohybrids had minimal cytotoxic effects on osteosarcoma MG-63 cells, while they showed remarkable cell proliferation even at low concentrations. Based on the in-vitro ALP, bioactivity and biocompatibility results, the content of ALP can directly reflect the activity or function of osteoblasts and is positively correlated with the mineralization ability of cells, which shows that pure and gold-doped Wollastonite nanohybrids were suitable candidates for bone regeneration/healing applications.
Due to its outstanding qualities, particularly when it takes the shape of hydrogels, chitosan is a well-known biological macromolecule with many applications. When chitosan hydrogels are modified with other polymers, the desirable function as skin regeneration hydrogels is compromised; nevertheless, the mechanical properties can be improved, which is crucial for commercialization. In this study, for the first time, bimetallic zinc silver metal-organic frameworks (ZAg MOF) loaded with ascorbic acid were added to chitosan/polyethylene oxide (PEO) based interpenetrating polymer network (IPN) hydrogels that were crosslinked with biotin to improve their antimicrobial activity, mechanical characteristics, and sustainable treatment of wounds. Significant changes in the microstructure, hydrophilicity level, and mechanical properties were noticed. Ascorbic acid release patterns were upregulated in an acidic environment pH (5.5) that mimics the initial wound pH. Impressive cell viability (98 %), antimicrobial properties, and almost full skin healing in a short time were achieved for the non-replaceable chitosan/PEO developed hydrogels. Enhancing the wound healing of the treated animals using the prepared CS/PEO hydrogel dressing was found to be a result of the inhibition of dermal inflammation via decreasing IL-1 beta, suppressing ECM degradation (MMP9), stimulating proliferation through upregulation of TGF-beta and increasing ECM synthesis as it elevates collagen 1 and alpha-SMA contents. The findings support the implementation of developed hydrogels as antimicrobial hydrogels dressing for fast skin regeneration.
Zn-MOF/bioactive glass nanoparticles were successfully prepared using quick–alkali-modified sol–gel and tested for gentamicin drug delivery. Samples of 0 and 0.8 mol% Zn MOF contents (BG and BG/Zn MOF, respectively) were characterized using XRD, FTIR, TEM, and SEM/EDX. In addition, zeta characteristics and surface area parameters were also evaluated. Moreover, the cell viability of the prepared samples was tested against the osteosarcoma MG-63 cell line to evaluate the ability of prepared samples for bone regeneration. In addition, the antimicrobial activity of glass samples with and without antibiotics was determined against different microorganisms. Finally, the samples were loaded with gentamicin drug, and drug release profile and kinetics were studied too. XRD and FTIR results confirmed the physicochemical properties of the prepared samples. TEM results showed that particles were in the nano-sized range in both samples; however, the presence of Zn MOF increased the dispersity of particles. Both samples were bioactive, as indicated by hydroxyapatite formation on their surfaces. Cytotoxicity estimation of prepared materials exhibited their safe and nontoxic nature. BG/Zn MOF sample demonstrated prolonged drug release and excellent antimicrobial activity in comparison to BG alone. Therefore, the present study provides promising preliminary results regarding the usage of BG/Zn MOF nanoparticles loaded with gentamicin as an effective approach for bone regeneration. Graphical Abstract
Mesoporous materials have reached a significant milestone in the last twenty years in the field of drug delivery, and they continue to be an important part of development and innovation in pharmacodynamics and pharma-cokinetics. In addition, their applications in the regeneration of hard tissues were greatly explored in recent decades due to their exponential biomineralization capabilities. They are the perfect candidates for active uptake and loading medicinal substances due to their unique chemical-physical properties. In this research, mesoporous zirconia (MZNs) and titania (MTNs) nanopowders were prepared by polymer sacrificial method as amoxicillin delivery systems. They were investigated using several characterization techniques including X-rays diffraction (XRD), Fourier transform infrared (FTIR), Transmittance electron microscopy (TEM) and Brunauer-Emmett-Teller (BET) surface area measurements. These techniques assist in evaluating the appropriate pore size and diameter, with emphasis on the safety of the released drugs. Amoxicillin release form MZNs and MTNs was conducted in Phosphate buffer saline (PBS) up to 28 days. The possibility of using these antibacterial agents against different strains of gram-positive and gram-negative bacteria has been evaluated. Finally viabilities of the human bone osteosarcoma cell line (MG-63) were tested. MZNs and MTNs demonstrate particle diameters in range of (8-25 nm) and they were confirmed as mesoporous particles by TEM and BET techniques. Amoxicillin loaded nanopowders showed good antibacterial and antifungal activities alongside with proliferation behavior after 24 h (124 and 110%) for MZNs & MTNs, respectively, and (189 and 114%) for amoxicillin loaded MZNs & MTNs, respectively. Therefore, the developed nanomaterials are of high potentiality to be implemented as medication delivery systems for bone regeneration.
Metal organic framework (MOF)-nanocages (MOF-NCs) in the form of zinc-based nanoparticles (NPs) were synthesized as drug carriers for the purpose of wound healing. The prepared NCs (single and bi-metallic with silver-MOF) were based on zinc and they were loaded with ascorbic acid (vitamin C) as a model drug which accelerates wound healing. The NCs were then investigated by several characterization techniques such as XRD, TEM, FTIR and BET surface area. Furthermore, the release behavior of the loaded ascorbic acid from the developed NCs was measured in phosphate buffer solution (PBS). NCs antibacterial activity was tested against strain of gram-positive bacteria (Staphylococcus aureus ATCC- 29213, Streptococcus pyogenes ATCC-19615 and Bacillus subtilis ATCC-6633), gram-negative bacteria strain (Pseudomonas aeruginosaATCC-27853and Escherichia coli ATCC-25922) and fungi (Candida albicans ATCC-10231).The physicochemical features of the NCs were confirmed by the results obtained from XRD and FTIR measurements. The particle size of the NCs was confirmed to be in the range of 30-50 nm. Prolonged drug release that was combined with impressive antibacterial activities, and good wound healing rates were also recognized for the zinc based NCs in comparison to commonly used Ag NPs. It is concluded that the current NCs are potentially suitable for wound healing and drug delivery applications.
This paper examined the preparation and characterization of lanthanum-doped phosphate glasses nanoparticles designed for effective management of bone regeneration and associated infections. Glasses incorporated different La2O3 contents (0, 5 and 10 mol%) were prepared successfully by a modified alkoxide sol-gel method. They were encoded as P0, PL5 and PL10. Specific surface area and the total pore volume of the glasses were found to decrease by the addition of La2O3 . TEM photos showed that glasses were spherical nanoparticles and incorporated uniform mesopores which increased in size by the increase of La2O3 contents. On the other hand, the dissolution of glasses nanoparticles was tested in different media (distilled H2O, SBF and tris-HCl buffer). The results showed that lanthanum-modified glasses demonstrated faster ionic release profiles of phosphate species relative to the base glass with faster dissolution from PL5 relative to PL10 in both distilled H2O and tris-HCl buffer. Furthermore, the possibility of using such glasses as a drug carrier was examined by loading the ciprofloxacin onto samples and studied its release profile. A sustained drug release profile from all phosphate glasses was achieved. Additionally, the incorporation of La2O3 in the modified glasses led to a prolonged drug release pattern relative to the base glass. The cytotoxicity test against BHK fibroblast cells showed that all phosphate nanoparticles were biocompatible. The viability of incubated cells with PL10 was > 97% suggesting that PL10 was not toxic up to 2.5 mg dose. However, a mild reduction of cell viability (93.3%) occurred at 5 mg, and at this dose, the cell viability increased in the following order P0 -> PL5 -> PL10, as it was 80, 87.4 and 93.3%. In conclusion, the long-term sustained pattern provided merely by the lanthanum-modified phosphate glasses nanoparticles implied the possibility of their application for localized osteomyelitis treatment.