Engineered Extracellular Vesicles: A potential treatment for regeneration.

Extracellular vesicles (EVs) play a critical role in various physiological and pathological processes. EVs have gained recognition in regenerative medicine due to their biocompatibility and low immunogenicity. However, the practical application of EVs faces challenges such as limited targeting ability, low yield, and inadequate therapeutic effects. To overcome these limitations, engineered EVs have emerged. This review aims to comprehensively analyze the engineering methods utilized for modifying donor cells and EVs, with a focus on comparing the therapeutic potential between engineered and natural EVs. Additionally, it aims to investigate the specific cell effects that play a crucial role in promoting repair and regeneration, while also exploring the underlying mechanisms involved in the field of regenerative medicine.

Regulatory Effects of Three-Dimensional Cultured Lipopolysaccharide-Pretreated Periodontal Ligament Stem Cell-Derived Secretome on Macrophages.

Phenotypic transformation of macrophages plays important immune response roles in the occurrence, development and regression of periodontitis. Under inflammation or other environmental stimulation, mesenchymal stem cells (MSCs) exert immunomodulatory effects through their secretome. It has been found that secretome derived from lipopolysaccharide (LPS)-pretreated or three-dimensional (3D)-cultured MSCs significantly reduced inflammatory responses in inflammatory diseases, including periodontitis, by inducing M2 macrophage polarization. In this study, periodontal ligament stem cells (PDLSCs) pretreated with LPS were 3D cultured in hydrogel (termed SupraGel) for a certain period of time and the secretome was collected to explore its regulatory effects on macrophages. Expression changes of immune cytokines in the secretome were also examined to speculate on the regulatory mechanisms in macrophages. The results indicated that PDLSCs showed good viability in SupraGel and could be separated from the gel by adding PBS and centrifuging. The secretome derived from LPS-pretreated and/or 3D-cultured PDLSCs all inhibited the polarization of M1 macrophages, while the secretome derived from LPS-pretreated PDLSCs (regardless of 3D culture) had the ability to promote the polarization of M1 to M2 macrophages and the migration of macrophages. Cytokines involved in the production, migration and polarization of macrophages, as well as multiple growth factors, increased in the PDLSC-derived secretome after LPS pretreatment and/or 3D culture, which suggested that the secretome had the potential to regulate macrophages and promote tissue regeneration, and that it could be used in the treatment of inflammation-related diseases such as periodontitis in the future.

Pretreated Mesenchymal Stem Cells and Their Secretome: Enhanced Immunotherapeutic Strategies.

Mesenchymal stem cells (MSCs) with self-renewing, multilineage differentiation and immunomodulatory properties, have been extensively studied in the field of regenerative medicine and proved to have significant therapeutic potential in many different pathological conditions. The role of MSCs mainly depends on their paracrine components, namely secretome. However, the components of MSC-derived secretome are not constant and are affected by the stimulation MSCs are exposed to. Therefore, the content and composition of secretome can be regulated by the pretreatment of MSCs. We summarize the effects of different pretreatments on MSCs and their secretome, focusing on their immunomodulatory properties, in order to provide new insights for the therapeutic application of MSCs and their secretome in inflammatory immune diseases.

Electrospun porous poly(3-hydroxybutyrate-co-4-hydroxybutyrate)/lecithin scaffold for bone tissue engineering.

Bone tissue engineering has emerged as a promising restorative strategy for bone reconstruction and bone defect repair. It is challenging to establish an appropriate scaffold with an excellent porous microstructure for bone defects and thereby promote bone repair. In this study, electrospinning as a simple and efficient technology was employed to fabricate a porous poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) scaffold coated with lecithin. The morphology, phase composition, and physical properties of the electrospun P34HB/lec scaffold were characterized. Meanwhile, cellular behaviors of bone marrow mesenchymal stem cells (BMSCs), including proliferation, adhesion, migration, osteogenic differentiation, and related gene expression, were also investigated. Finally, a rat subcutaneous implant model and a calvarial defect model were used to evaluated the biocompatibility and effect of these scaffolds on bone repair, respectively. The in vitro results demonstrated that these electrospun fibers were interwoven with each other to form the porous P34HB/lec scaffold and the addition of lecithin improved the hydrophilicity of the pure P34HB scaffold, enhanced the efficiency of cell migration, and decreased inflammatory response. Furthermore, the in vivo results showed that P34HB/lec scaffold had excellent biocompatibility, improved the vascularization, and promoted the bone regeneration. All these results indicated that nanofibers of P34HB scaffolds in combination with the lecithin could exert a synergistic effect on promoting osteogenesis and regeneration of bone defects; thus, the P34HB scaffold with lecithin showed great application potential for bone tissue engineering.

Supramolecular Hydrogel Based on an Osteogenic Growth Peptide Promotes Bone Defect Repair.

Current bone defect treatment strategies are associated with several risks and have major limitations. Therefore, it is necessary to develop an inexpensive growth factor delivery system that can be easily produced in large quantities and can promote long-term bone regeneration. An osteogenic growth peptide (OGP) is a 14 amino acid peptide with a short peptide sequence active fragment. In this study, we developed two OGP-based self-assembling supramolecular hydrogels (F- and G-sequence hydrogels) and investigated the in vitro and in vivo effects on proliferation and osteogenesis, including the mechanism of hydrogel-mediated bone defect repair. The hydrogels presented excellent biocompatibility and cell proliferation-promoting properties (1.5-1.7-fold increase). The hydrogels could effectively upregulate the expression of osteogenic factors, including RUNX2, BMP2, OCN, and OPN, to promote osteogenesis differentiation. Interestingly, 353 differentially expressed genes were identified in hBMSCs treated with hydrogels. The hydrogels were proved to be involved in the inflammatory pathways and folate-related pathways to mediate the osteogenesis differentiation. Furthermore, the therapeutic efficiency (bone volume/total volume, trabecular number, and bone mineral density) of hydrogels on bone regeneration in vivo was evaluated. The results showed that the hydrogels promoted bone formation in the early stage of bone defect healing. Taken together, this study was the first to develop and evaluate the properties of OGP-based self-assembling supramolecular hydrogels. Our study will provide inspiration for the development of delivering OGP for bone regeneration.

Remediation of Pb-Contaminated Soil Using a Novel Magnetic Nanomaterial Immobilization Agent.

The management of heavy metal contaminated soil has received extensive research attention. In this study, a novel immobilization agent (SiO2@Fe3O4@C-COOH) was combined with traditional immobilization agents (TIAs), i.e., CaO, organic matter (OM), and calcium superphosphate (CSP), and used to remediate Pb-contaminated soil. The immobilization effects of Pb in soil was evaluated through pot experiments involving wheat cultivation. The results indicated that SiO2@Fe3O4@C-COOH delivered a higher Pb immobilization efficiency than did TIAs such as CaO, OM, and CSP. The application of SiO2@Fe3O4@C-COOH in combination with TIAs (CaO, OM, and CSP) synergistically enhanced the Pb immobilization efficiency of the soil to 85.10%. Further, joint application in a 54.19% reduction of Pb content in wheat roots, a 65.78% reduction in stems, and a 47.96% in leaves. Thus, the combined application of SiO2@Fe3O4@C-COOH and TIAs significantly reduced the bioavailability of Pb, achieved the purpose of Pb stabilization and soil remediation, and has the potential for wide-spread application in the remediation of Pb-contaminated soils.

[Effect of osthole on periodontal remodeling during orthodontic tooth movement in rats].

PURPOSE: To investigate the effect of osthole on periodontal remodeling during orthodontic tooth movement (OTM) in rats. METHODS: Seventy two 8-week-old male SD rats were randomly equally divided into 3 groups: two experimental groups of osthole with low (20 mg/kg) and high (40 mg/kg) concentration and the control group. Models of OTM were routinely established. Rats in the experimental groups were respectively given osthole by intragastric administration, while rats in the control group received the same volume of solvent. The rats were sacrificed on 7th, 14th, 21st and 28th day after orthodontic treatment, and the maxilla was harvested and the distance between the first and second molar was measured in each stage. Hematoxylin-eosin (H-E) staining, tartrate resistant acid phosphatase (TRACP) staining were performed. The results were analyzed with SPSS 20.0 software package for one-way analysis of variance. RESULTS: The mesio-moving distance of the three groups successively increased gradually. On the 7th day, there was no difference between the low concentration group and the control group (P>0.05); at other time point, the experimental groups exhibited significant differences from the control group(P<0.05), and the high concentration group had more obviously mesio-movement than the low concentration group(P<0.05). Histological observation showed that in the tension side, osteoblast appeared, but more apparent in the experimental groups than in the control group. In the pressure side, the number of osteoclast reached the peak at the 7th day, and much more osteoclasts were seen in the experimental groups than in the control group (P<0.05), in high concentration group than in low concentration group (P<0.05). The number of osteoclast decreased subsequently, but significant difference existed between the experimental groups and the control group (P<0.05) on the 14th day. At other time points, there was no significant difference among the three groups(P>0.05). CONCLUSIONS: Osthole could increase the number of osteoclast in periodontium and promote bone remodeling at the early stage of treatment, its effect is dose-dependence during OTM.

Short-term effects of nicotine on orthodontically induced root resorption in rats.

OBJECTIVE: To investigate the effect of nicotine exposure on root resorption in an in vivo rat model of orthodontic tooth movement (OTM), and its association with odontoclastogenesis and receptor activator of nuclear factor-kappa B ligand (RANKL) expression. MATERIALS AND METHODS: Forty-eight 10-week-old male Wistar rats were divided into three groups. The negative control group was untreated. The left maxillary first molars in the nicotine-treated group and the positive control group received OTM with an initial force of 0.6 N in the mesial direction. Also, the nicotine-treated group received intraperitoneal injection of nicotine at 7 mg/kg per day. After 21 days, the rats were humanely killed. Eight rats from each group were randomly chosen for crater volume analysis by micro-computed tomography. For the remaining eight rats in each group, specimen slices were generated for histologic examination to determine the odontoclast number and the mean optical density value of RANKL. RESULTS: The resorption volumes in the nicotine-treated group were significantly larger than those in the control groups. Also, the nicotine-treated group displayed significantly higher number of odontoclasts and elevated RANKL expression compared to the control groups. CONCLUSIONS: In an in vivo rat model, nicotine exposure promotes odontoclastogenesis and RANKL expression, evoking aggravated root resorption during OTM.

Assessing changes in quality of life using the Oral Health Impact Profile (OHIP) in patients with different classifications of malocclusion during comprehensive orthodontic treatment.

BACKGROUND: The objectives of this study were to investigated changes in OHRQoL among patients with different classifications of malocclusion during comprehensive orthodontic treatment. METHODS: Clinical data were collected from 81 patients (aged 15 to 24) who had undergone comprehensive orthodontic treatment. Participants were classified 3 groups: Class I (n = 35), II (n = 32) and III (n = 14) by Angle classification. OHRQoL was assessed using the Oral Health Impact Profile (OHIP-14). All subjects were examined and interviewed at baseline (T0), after alignment and leveling (T1), after correction of molar relationship and space closure (T2), after finishing (T3). Friedman 2-way analysis of variance (ANOVA) and Wilcoxon signed rank tests were used to compare the relative changes of OHRQoL among the different time points. A Bonferroni correction with P < 0.005 was used to declare significance. RESULTS: Significant reductions were observed in all seven OHIP-14 domains of three groups except for social disability (P > 0.005) in class I and class II, Handicap in class II and class III (P > 0.005). Class I patients showed significant changes for psychological disability and psychological discomfort domain at T1, functional limitation, physical pain at T2. Class III patients showed a significant benefit in all domains except physical pain and functional limitation. Class II patients showed significant changes in the physical pain, functional disability, and physical disability domains at T1. CONCLUSIONS: The impact of comprehensive orthodontic treatment on patients' OHRQoL do not follow the same pattern among patients with different malocclusion. Class II patients benefits the most from the stage of space closure, while class I patients benefits the first stage (alignment and leveling) of treatment in psychological disability and psychological discomfort domains.

Effects of icariin on orthodontic tooth movement in rats.

PURPOSE: Orthodontic tooth movement (OTM) is achieved through bone remodeling of the alveolar bone. Icariin, the active ingredient isolated from Herba Epimedii which is a traditional Chinese medicine (TCM) commonly used for osteoporosis treatment in China. The purpose of the study is to explore the effect of icariin on OTM in rats, and analyze the possible mechanism involved. METHODS: 48 rats were selected and divided into 2 groups: the control group and the experimental group. Rats in the experimental group were given 20 mg/kg/day icariin by intragastric administration, while the control group received the same volume solvent. All rats were placed a closed coil spring between their upper first molar and incisor, exerting a force of about 40 g to establish animal models of OTM. As the first molar moved mesially, a space between the first and second molar was created. The rats were sacrificed in batch on the 7th, 14th, 21st and 28th days after orthodontic treatment. The amount of tooth movement was measured, and histomorphometric analysis based on slices from periodontium adjacent to the maxillary first molars were used to observe new bone formation, bone resorption and quantify osteoclasts. KEY RESULTS: Icariin increased OTM (P<0.05) by 65.2%, 35.3%, 11.7% and 16.7% on day 7, 14, 21, 28 respectively compared with the control group. The number of osteoclasts in the icariin group showed a transient but sudden increase and then a persistent decrease. CONCLUSIONS: Icariin could accelerate OTM in rats through promoting bone remodeling of alveolar bone.

Effects of strontium ranelate on bone formation in the mid-palatal suture after rapid maxillary expansion.

BACKGROUND: The aim of this experimental study was to investigate the effects of strontium ranelate on bone regeneration in the mid-palatal suture in response to rapid maxillary expansion (RME). METHODS: Thirty-six male 6-week-old Wistar rats were randomly divided into three groups, ie, an expansion only (EO) group, an expansion plus strontium ranelate (SE) group, and a control group. An orthodontic appliance was set between the right and left upper molars of rats with an initial expansive force of 0.98 N. Rats in the SE group were administered strontium ranelate (600 mg/kg body weight) and then euthanized in batches on days 4, 7, and 10. Morphological changes in the mid-palatal suture were investigated using micro-computed tomography and hematoxylin and eosin staining after RME. Bone morphogenetic protein-2 expression in the suture was also examined to evaluate bone formation in the mid-palatal suture. Image-Pro Plus software was then used to determine the mean optical density of the immunohistochemical images. Analysis of variance was used for statistical evaluation at the P<0.05 level. RESULTS: With expansive force, the mid-palatal suture was expanded, but there was no statistically significant difference (P>0.05) between the SE and EO groups. The bone volume of the suture decreased after RME, but was higher in the SE group than in the EO group on days 7 and 10. Further, expression of bone morphogenetic protein-2 in the SE group was higher than in the other two groups (P<0.05). CONCLUSION: Strontium ranelate may hasten new bone formation in the expanded mid-palatal suture, which may be therapeutically beneficial in prevention of relapse and shortening the retention period after RME.