Targeted drug delivery of engineered mesenchymal stem/stromal-cell-derived exosomes in cardiovascular disease: recent trends and future perspectives.

In recent years, stem cells and their secretomes, notably exosomes, have received considerable attention in biomedical applications. Exosomes are cellular secretomes used for intercellular communication. They perform the function of intercellular messengers by facilitating the transport of proteins, lipids, nucleic acids, and therapeutic substances. Their biocompatibility, minimal immunogenicity, targetability, stability, and engineerable characteristics have additionally led to their application as drug delivery vehicles. The therapeutic efficacy of exosomes can be improved through surface modification employing functional molecules, including aptamers, antibodies, and peptides. Given their potential as targeted delivery vehicles to enhance the efficiency of treatment while minimizing adverse effects, exosomes exhibit considerable promise. Stem cells are considered advantageous sources of exosomes due to their distinctive characteristics, including regenerative and self-renewal capabilities, which make them well-suited for transplantation into injured tissues, hence promoting tissue regeneration. However, there are notable obstacles that need to be addressed, including immune rejection and ethical problems. Exosomes produced from stem cells have been thoroughly studied as a cell-free strategy that avoids many of the difficulties involved with cell-based therapy for tissue regeneration and cancer treatment. This review provides an in-depth summary and analysis of the existing knowledge regarding exosomes, including their engineering and cardiovascular disease (CVD) treatment applications.

Ultrasound Responsive Smart Implantable Hydrogels for Targeted Delivery of Drugs: Reviewing Current Practices.

Over the last two decades, the process of delivering therapeutic drugs to a patient with a controlled release profile has been a significant focus of drug delivery research. Scientists have given tremendous attention to ultrasound-responsive hydrogels for several decades. These smart nanosystems are more applicable than other stimuli-responsive drug delivery vehicles (ie UV-, pH- and thermal-, responsive materials) because they enable more efficient targeted treatment via relatively non-invasive means. Ultrasound (US) is capable of safely transporting energy through opaque and complex media with minimal loss of energy. It is capable of being localized to smaller regions and coupled to systems operating at various time scales. However, the properties enabling the US to propagate effectively in materials also make it very difficult to transform acoustic energy into other forms that may be used. Recent research from a variety of domains has attempted to deal with this issue, proving that ultrasonic effects can be used to control chemical and physical systems with remarkable specificity. By obviating the need for multiple intravenous injections, implantable US responsive hydrogel systems can enhance the quality of life for patients who undergo treatment with a varied dosage regimen. Ideally, the ease of self-dosing in these systems would lead to increased patient compliance with a particular therapy as well. However, excessive literature has been reported based on implanted US responsive hydrogel in various fields, but there is no comprehensive review article showing the strategies to control drug delivery profile. So, this review was aimed at discussing the current strategies for controlling and targeting drug delivery profiles using implantable hydrogel systems.

Effect of High Positive Acceleration (+Gz) Environment on Dental Implant Osseointegration:A Preliminary Animal Study.

OBJECTIVE: To observe the effect of high positive acceleration (+Gz) environment on dental implant osseointegration in a rabbit model and to investigate its mechanism. METHODS: Forty-eight New Zealand white rabbits were randomly divided into 6 groups. The rabbit's mandibular incisors were extracted and 1 implant was placed in each socket immediately. After 1 week of rest, the rabbits were exposed to a high +Gz environment, 3 times a week. The rabbits were sacrificed at 3 weeks (2 weeks +Gz exposure), 5 weeks (4 weeks +Gz exposure), and 12 weeks (4 weeks +Gz exposure and 7 weeks normal environment) after surgery, respectively. Specimens were harvested for micro-CT scanning, histological analysis, and real-time polymerase chain reaction examination. RESULTS: Compared with those in the control group, the mRNA expression levels of bone morphogenetic protein-2 (BMP-2), osteopontin (OPN), and transforming growth factor-ß1 (TGF-ß1) were significantly lower (P < 0.05), while the mRNA expression level of receptor activator of nuclear factor κB ligand (RANKL) and the RANKL/osteoprotegerin (OPG) ratio were significantly higher (P < 0.05) at 3 weeks; values of bone volume fraction, trabecular number, bone-implant contact (BIC), and TGF-ß1 and OPG mRNA expression levels were significantly lower (P < 0.05), and the value of trabecular separation, RANKL mRNA expression level and RANKL/OPG ratio were significantly higher (P < 0.05) at 5 weeks; and the value of BIC was still significantly lower (P < 0.05) at 12 weeks in the experimental group. CONCLUSION: Early exposure to the high +Gz environment after implant surgery might have an adverse effect on osseointegration, and its mechanism could be related to the inhibition of osteoblast activity and promotion of osteoclast activity.

[Comparison and analysis of human dentin matrix protein 1 promoter activity in three different cells].

OBJECTIVE: To observe and compare the luciferase activities of different length segments of human dentin matrix protein 1 promoter in human dental pulp stem cells (HDPSC), osteoblasts (OC) and Hela cells. METHODS: The differentlength desired DNA segments were obtained from 2 195 bp Dmp1 promoter cloned by PCR method. The amplified promoter segments with different length were cloned into luciferase report gene vector pGL3-Basic, the correct orientation of those inserts was verified by cutting with two different restrict enzymes. The luciferase activity was observed after different pGL3-PDmp1 vectors were transfected transiently into those three different-type cells. RESULTS: 6 Dmp1 promoter segments with different-length were obtained successfully, and luciferase report gene vectors with different promoter segments were successfully constructed after identified by restriction enzymes cutting. They had different luciferase activities when they were transfected transiently into HDPSC, and the region of -505(-)-193 bp and -935(-)-505 bp could be regarded as the specific promoters of Dmp1 promoter for HDPSC and OC respectively, which could include the basic regulatory elements. CONCLUSION: The correct clone of the upstream of human Dmp1 promoter segments with different length had been obtained, and they had strong luciferase activities in HDPSC and OC, but very low in Hela cell. These results will make an important basis for studying mineralized tissue-specific transcriptional regulation mechanisms of Dmp1.