Atomic layer deposited TiO2 nanofilm on titanium implant for reduced the release of particles.

Objective: Titanium implants are widely used in surgeries for their biocompatibility and mechanical properties. However, excessive titanium particle release can cause implant failure. This study explores Atomic Layer Deposition (ALD) to coat commercially pure titanium (Cp-Ti) with TiO2, aiming to improve its frictional and corrosion resistance while reducing particle release. By comparing TiO2 films with varying ALD cycle numbers, we assess surface properties, particle release, friction, and corrosion performance, providing insights into mitigating particle release from implants. Methods: Cp-Ti surfaces were prepared and coated with TiO2 films of 100, 300, and 500 ALD cycles. Surface characterization involved SEM, EDX, and XRD. Friction was tested using SEM, nanoindentation, and ICP-MS. Corrosion resistance was evaluated through immersion tests and electrochemical analysis. Cytotoxicity was assessed using BMSCs. Results: Surface characterization revealed smoother surfaces with increased ALD cycles, confirming successful TiO2 deposition. Friction testing showed reduced friction coefficients with higher ALD cycles, supported by nanoindentation results. Corrosion resistance improved with increasing ALD cycles, as evidenced by electrochemical tests and reduced titanium release. Cytotoxicity studies showed no significant cytotoxic effects. Conclusion: ALD-coated TiO2 films significantly enhance frictional and corrosion resistance of titanium implants while reducing particle release. The study underscores the importance of ALD cycle numbers in optimizing film performance, offering insights for designing implants with improved properties.

Cellular Uptake of Engineered Extracellular Vesicles: Biomechanisms, Engineered Strategies, and Disease Treatment.

Extracellular vesicles (EVs), lipid-enclosed nanosized membrane vesicles, are regarded as new vehicles and therapeutic agents in intercellular communication. During internal circulation, if EVs are not effectively taken up by recipient cells, they will be cleared as "cellular waste" and unable to deliver therapeutic components. It can be seen that cells uptake EVs are the prerequisite premise for sharing intercellular biological information. However, natural EVs have a low rate of absorption by their recipient cells, off-target delivery, and rapid clearance from circulation, which seriously reduces the utilization rate. Affecting the uptake rate of EVs through engineering technologies is essential for therapeutic applications. Engineering strategies for customizing EV uptake can potentially overcome these limitations and enable desirable therapeutic uses of EVs. In this review, the mechanism and influencing factors of natural EV uptake will be described in detail. Targeting each EV uptake mechanism, the strategies of engineered EVs and their application in diseases will be emphatically discussed. Finally, the future challenges and perspectives of engineered EVs are presented multidimensionally.

Melatonin pretreatment on exosomes: Heterogeneity, therapeutic effects, and usage.

The therapeutic outcomes of exosome-based therapies have greatly exceeded initial expectations in many clinically intractable diseases due to the safety, low toxicity, and immunogenicity of exosomes, but the production of the exosomes is a bottleneck for wide use. To increase the yield of the exosomes, various solutions have been tried, such as hypoxia, extracellular acidic pH, etc. With a limited number of cells or exosomes, an alternative approach has been developed to improve the efficacy of exosomes through cell pretreatment recently. Melatonin is synthesized from tryptophan and secreted in the pineal gland, presenting a protective effect in pathological conditions. As a new pretreatment method, melatonin can effectively enhance the antioxidant, anti-inflammatory, and anti-apoptotic function of exosomes in chronic kidney disease, diabetic wound healing, and ischemia-reperfusion treatments. However, the current use of melatonin pretreatment varies widely. Here, we discuss the effects of melatonin pretreatment on the heterogeneity of exosomes based on the role of melatonin and further speculate on the possible mechanisms. Finally, the therapeutic use of exosomes and the usage of melatonin pretreatment are described.

Promotion or inhibition of extracellular vesicle release: Emerging therapeutic opportunities.

Extracellular vesicles (EVs) are vehicles of intercellular communication that are released from various cell types under physiological and pathological conditions, with differing effects on the body. Under physiological conditions, EVs mediate cell-to-cell and intertissue communication and participate in maintaining homeostasis. Certain EV types have emerged as biological therapeutic agents in various fields, such as cell-free regenerative medicine, drug delivery and immunotherapy. However, the low yield of EVs is a bottleneck in the large-scale implementation of these therapies. Conversely, more EVs in the microenvironment in other circumstances, such as tumor metastasis, viral particle transmission, and the propagation of neurodegenerative disease, can exacerbate the situation, and the inhibition of EV secretion may delay the progression of these diseases. Therefore, the promotion and inhibition of EV release is a new and promising field because of its great research potential and wide application prospects. We first review the methods and therapeutic opportunities for the regulation of EV release based on the mechanism of EV biogenesis and consider the side effects and challenges.

Correction: Nanozymes go oral: nanocatalytic medicine facilitates dental health.

Correction for 'Nanozymes go oral: nanocatalytic medicine facilitates dental health' by Xiaohang Chen et al., J. Mater. Chem. B, 2021, 9, 1491-1502, DOI: 10.1039/d0tb02763d.

Effects of Impacted Lower Third Molar Extraction on Periodontal Tissue of the Adjacent Second Molar.

The extraction of impacted lower third molars (ILTM) is one of the most common procedures in oral-maxillofacial surgery. Being adjacent to lower second molars, most impacted lower third molars often lead to distal periodontal defects of adjacent second molars. Several symptoms may occur after extraction, such as periodontal pocket formation, loss of attachment, alveolar bone loss and even looseness of second molar resulting in extraction. The distal periodontal defects of second molars are affected by many factors, including periodontal conditions, age, impacted type of third molars, and intraoperative operations. At present, several studies have suggested that dentists can reduce the risk of periodontal defects of the second molar after ILTM extraction through preoperative evaluation, reasonable selection of flap design, extraction instruments and suture type, and necessary postoperative interventions. This review summarizes the research progress on the influence factors, interventions methods and some limitations of distal periodontal defects of adjacent second molar after extraction of impacted mandibular third molars, with the aim of opening up future directions for studying effects of ILTM extraction on periodontal tissue of the adjacent second molar.

The unfavorable role of titanium particles released from dental implants.

Titanium is considered to be a metal material with the best biological safety. Studies have proved that the titanium implanted in the bone continuously releases titanium particles (Ti particles), significantly increasing the total titanium content in human body. Generally, Ti particles are released slowly without causing a systemic immune response. However, the continuous increased local concentration may result in damage to the intraepithelial homeostasis, aggravation of inflammatory reaction in the surrounding tissues, bone resorption and implant detachment. They also migrate with blood flow and aggregate in the distal organ. The release of Ti particles is affected by the score of the implant surface structure, microenvironment wear and corrosion, medical operation wear, and so on, but the specific mechanism is not clear. Thus, it difficult to prevent the release completely. This paper reviews the causes of the Ti particles formation, the damage to the surrounding tissue, and its mechanism, in particular, methods for reducing the release and toxicity of the Ti particles.

Nanozymes go oral: nanocatalytic medicine facilitates dental health.

Nanozymes are multi-functional nanomaterials with enzyme-like activity, which rapidly won a place in biomedicine due to their number of nanocatalytic materials types and applications. Yan and Gao first discovered horseradish peroxidase-like activity in ferromagnetic nanoparticles in 2007. With the joint efforts of many scientists, a new concept-nanocatalytic medicine-is emerging. Nanozymes overcome the inherent disadvantages of natural enzymes, such as poor environmental stability, high production costs, difficult storage and so on. Their progress in dentistry is following the advancement of materials science. The oral research and application of nanozymes is becoming a new branch of nanocatalytic medicine. In order to highlight the great contribution of nanozymes facilitating dental health, we first review the overall research progress of multi-functional nanozymes in oral related diseases, including treating dental caries, dental pulp diseases, oral ulcers and peri-implantitis; the monitoring of oral cancer, oral bacteria and ions; and the regeneration of soft and hard tissue. Additionally, we also propose the challenges remaining for nanozymes in terms of their research and application, and mention future concerns. We believe that the new catalytic nanomaterials will play important roles in dentistry in the future.

Modulation of in vitro phagocytic uptake and immunogenicity potential of modified Herceptin®-conjugated PLGA-PEG nanoparticles for drug delivery.

There is an increasing interest in engineered nanoparticle (NP) conjugates for targeted and controlled drug delivery. However, the practical applications of these NP delivery vehicles remain constrained because of their reactivity with the body's immune system defenses resulting in undesirable off-target effects. In this study, poly(D,L lactide-co-glycolide) (PLGA)-b-polyethylene glycol (PEG) NPs conjugated to different quantities of the commercial antibody Herceptin® meant to target HER2-positive breast cancer cells were studied for their immune cell uptake and immunogenic properties (using murine macrophages and human dendritic cells). We further modified the Herceptin®-NP conjugates with short PEG linkers with an aim to increase their biocompatibility. The 50% Herceptin®-NP conjugate group with short PEG modification to Herceptin® showed the best reduction in immune cell uptake by 82% along with the reduction by >50% for proinflammatory cytokine response (TNF-α and IL-6). In conclusion, optimum Herceptin® coverage with improved hydrophilic profile results in reduced phagocytic uptake and immunogenicity of engineered NP-antibody conjugates, potentially minimizing their undesirable off-target effects as a drug delivery vehicle.

Delayed Sequential Co-Delivery of Gefitinib and Doxorubicin for Targeted Combination Chemotherapy.

There are an increasing number of studies showing the order of drug presentation plays a critical role in achieving optimal combination therapy. Here, a nanoparticle design is presented using ion pairing and drug-polymer conjugate for the sequential delivery of gefitinib (Gi) and doxorubicin (Dox) targeting epidermal growth factor receptor (EGFR) signaling applicable for the treatment of triple negative breast cancers. To realize this nanoparticle design, Gi complexed with dioleoyl phosphatidic acid (DOPA) via ion paring was loaded onto the nanoparticle made of Dox-conjugated poly(l-lactide)-block-polyethylene glycol (PLA-b-PEG) and with an encapsulation efficiency of ∼90%. The nanoparticle system exhibited a desired sequential release of Gi followed by Dox, as verified through release and cellular uptake studies. The nanoparticle system demonstrated approximate 4-fold and 3-fold increases in anticancer efficacy compared to a control group of Dox-PLA-PEG conjugate against MDA-MB-468 and A549 cell lines in terms of half maximal inhibitory concentration (IC50), respectively. High tumor accumulation of the nanoparticle system was also substantiated for potential in vivo applicability by noninvasive fluorescent imaging.

Sequential delivery of erlotinib and doxorubicin for enhanced triple negative Breast cancer treatment using polymeric nanoparticle.

Recent studies of signaling networks point out that an order of drugs to be administrated to the cancerous cells can be critical for optimal therapeutic outcomes of recalcitrant metastatic and drug-resistant cell types. In this study, a development of a polymeric nanoparticle system for sequential delivery is reported. The nanoparticle system can co-encapsulate and co-deliver a combination of therapeutic agents with different physicochemical properties [i.e. epidermal growth factor receptor (EGFR) inhibitor, erlotinib (Ei), and doxorubicin (Dox)]. Dox is hydrophilic and was complexed with anionic lipid, 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA), via ion pairing to form a hydrophobic entity. Then it was co-encapsulated with hydrophobic Ei in a poly(L-lactide)-b-polyethylene glycol (PLA-b-PEG) nanoparticle by nanoprecipitation. The complexation of Dox with DOPA greatly helps the encapsulation of Dox, and substantially reduces the release rate of Dox. This nanoparticle system was found to burst the release of Ei with a slow and sustained profile of Dox, which is an optimal course of administration for these two drugs as previously reported. The efficacy of this sequential delivery nanoparticle system was validated in vitro and its in vivo potential applicability was substantiated by fluorescent imaging of high tumor accumulation.

Calcium phosphate-polymer hybrid nanoparticles for enhanced triple negative breast cancer treatment via co-delivery of paclitaxel and miR-221/222 inhibitors.

In this study, a development of a novel calcium phosphate-polymer hybrid nanoparticle system is reported.The nanoparticle system can co-encapsulate and co-deliver a combination of therapeutic agents with different physicochemical properties (i.e., inhibitors for microRNA-221 and microRNA-222 (miRi-221/222) and paclitaxel (pac)).miRi-221/222 are hydrophilic and were encapsulated with calcium phosphate by co-precipitation in a water-in-oil emulsion.The precipitates were then coated with an anionic lipid, dioleoylphosphatidic acid (DOPA), to co-encapsulate hydrophobic paclitaxel outside the hydrophilic precipitates and inside the same nanoparticle.The nanoparticles formed by following this approach had a size of about ≤100nm and contained both lipid-coated calcium phosphate/miRi and paclitaxel.This nanoparticle system was found to simultaneously deliver paclitaxel and miRi-221/222 to their intracellular targets, leading to inhibit proliferative mechanisms of miR-221/222 and thus significantly enhancing the therapeutic efficacy of paclitaxel.

Herceptin conjugated PLGA-PHis-PEG pH sensitive nanoparticles for targeted and controlled drug delivery.

A dual functional nano-scaled drug carrier, comprising of a targeting ligand and pH sensitivity, has been made in order to increase the specificity and efficacy of the drug delivery system. The nanoparticles are made of a tri-block copolymer, poly(d,l lactide-co-glycolide) (PLGA)-b-poly(l-histidine) (PHis)-b-polyethylene glycol (PEG), via nano-precipitation. To provide the nanoparticle feature of endolysosomal escape and pH sensitivity, poly(l-histidine) was chosen as a proton sponge polymer. Herceptin, which specifically binds to HER2 antigen, was conjugated to the nanoparticles through click chemistry. The nanoparticles were characterized via dynamic light scattering (DLS) and transmission electron microscopy (TEM). Both methods showed the sizes of about 100nm with a uniform size distribution. The pH sensitivity was assessed by drug releases and size changes at different pH conditions. As pH decreased from 7.4 to 5.2, the drug release rate accelerated and the size significantly increased. During in vitro tests against human breast cancer cell lines, MCF-7 and SK-BR-3 showed significantly increased uptake for Herceptin-conjugated nanoparticles, as compared to non-targeted nanoparticles. Herceptin-conjugated pH-sensitive nanoparticles showed the highest therapeutic effect, and thus validated the efficacy of a combined approach of pH sensitivity and active targeting.