3D-Printed Polycaprolactone-Based Containing Calcium Zirconium Silicate: Bioactive Scaffold for Accelerating Bone Regeneration.

There is an essential clinical need to develop rapid process scaffolds to repair bone defects. The current research presented the development of calcium zirconium silicate/polycaprolactone for bone tissue engineering utilising melt extrusion-based 3D printing. Calcium zirconium silicate (CZS) nanoparticles were added to polycaprolactone (PCL) porous scaffolds to enhance their biological and mechanical properties, while the resulting properties were studied extensively. No significant difference was found in the melting point of the samples, while the crystallisation temperature points of the samples containing bioceramic increased from 36.1 to 40.2 °C. Thermal degradation commenced around 350 °C for all materials. According to our results, increasing the CZS content from 0 to 40 wt.% (PC40) in porous scaffolds (porosity about 55-62%) improved the compressive strength from 2.8 to 10.9 MPa. Furthermore, apatite formation ability in SBF solution increased significantly by enhancing the CZS percentage. According to MTT test results, the viability of MG63 cells improved remarkably (~29%) in PC40 compared to pure PCL. These findings suggest that a 3D-printed PCL/CZS composite scaffold can be fabricated successfully and shows great potential as an implantable material for bone tissue engineering applications.

Compared to oxcarbazepine and carbamazepine, botulinum toxin type A is a useful therapeutic option for trigeminal neuralgia symptoms: A systematic review.

OBJECTIVES: This review aimed to compare the effectiveness of three treatments: BTX A, CBZ, and OXB, in managing trigeminal neuralgia (TN). MATERIAL AND METHODS: We conducted a thorough search for research articles related to our issue using specific keywords on several databases, including Cochrane Central Register of Controlled Trials, Science Direct, Scopus, PubMed, Elsevier, Springer Journals, Ovid Medline, EBSCO, and Web of Science. Our focus was on publications from 1965 to 2023. RESULTS: We retrieved 46 articles from the search and reviewed them carefully. Out of these, we selected 29 articles that met the inclusion criteria. Among the selected articles, 11 investigated the effects of CBZ and OXB, while 18 explored the impact of BTX A on the improvement of TN symptoms. The response rate ranged between 56% and 90.5% for CBZ and between 90.9% and 94% for OXB. The response rate for BTX A ranged between 51.4% and 100%. All these three treatments had a remarkable effect on the improvement of TN. Importantly, findings highlighted that side effects of CBZ and OXB could lead to treatment discontinuation in some cases, whereas BTX A's side effects have been minimal and less frequent. CONCLUSIONS: Consequently, BTX A emerges as a promising alternative for TN treatment. However, additional clinical trials are necessary to validate this finding, and further research is required to establish a standardized protocol for administering BTX A in TN.

Effect of 980 nm photobiomodulation delivered by a handpiece with Gaussian vs. Flat-Top profiles on proliferation and differentiation of buccal fat pad stem cells.

The aim of this study was to compare the effectiveness of the Gaussian and Flat-Top profiles in proliferation and differentiation of mesenchymal stem cell of buccal fat pad. Based on the timing schedule and type of laser handpieces, the cells were assigned to a control group with no radiation, and two irradiation test groups (980 nm) with Flat-Top (F) (power of 1.1 W, beam area of 1 cm2 ) and standard Gaussian (G) (power of 0.7 W, beam area of 0.5 cm2 ) handpieces. Each test group was divided into three subgroups, receiving one time (60 J/cm2 ), two times (120 J/cm2 ), and three times (180 J/cm2 ) irradiation. 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and Annexin V tests were performed. The Alizarin Red staining and polymerase chain reaction tests were done both at the beginning and the end of the first and second weeks. The degree of mineralization and expression of osteogenic markers, RUNX2, OCN, and OPN were evaluated. Based on the MTT and Annexin V test results, both test groups outperformed the control group in degrees of cell proliferation during the first day of laser irradiation (p < 0.05). After one and two times irradiation, the expression of osteogenic markers in the test groups was significantly higher than the control group. PBM with Flat-Top and Gaussian handpieces can enhance ossification and cell differentiation regardless of the type of handpieces.

Comparison of low-level laser therapy and standard treatment for temporomandibular disorders: An assessment of therapeutic and placebo effects.

BACKGROUND: Despite extensive research on the use of low-power lasers for TMD treatment, the extent of their effectiveness remains uncertain. OBJECTIVE: This study aimed to investigate the therapeutic or placebo effect of LLLT for TMD, and to compare it with standard treatment methods. A unique aspect of this study was the inclusion of a control group that received only standard treatment, allowing for an assessment of the placebo effect of LLLT. METHODS: A total of 42 patients with TMD were referred to Kerman Dental School Pain Clinic and were randomly assigned to three groups: group A received LLLT, group B was a placebo group and group C was a control group that received only standard treatment. The laser groups received gallium-aluminium-arsenide laser treatment twice a week for 10 sessions. Patients' jaw movement rate indicators and VAS index were evaluated at the start of treatment, and indicators were re-recorded every week for 5 weeks. SPSS 21 was used for statistical analysis, including ANOVA and Tukey's post hoc tests for inter-group comparisons. The repeated measurement test was used to analyse the data. RESULTS: All groups showed significant improvement in VAS indicators (p = .0001), lateral jaw movements (p = .0001), forward jaw movement (p = .007) but not for maximum mouth opening. No significant difference was observed between the groups at the end of the study (p = .000). CONCLUSION: Our study provides insights into LLLT's effectiveness for TMD, suggesting it cannot replace standard treatment alone. These findings contribute to the literature and emphasise the importance of including a control group in future studies to assess the placebo effect of LLLT.

Temporomandibular treatments are significantly efficient in improving otologic symptoms.

Symptoms of temporomandibular disorders (TMD) could be present as otologic symptoms like earache and dizziness in some patients. In most cases, these symptoms are not recognized because otolaryngologists fail to diagnose TMD as a source of the problem. This investigation was conducted to evaluate the effect of TMD treatments on the otologic symptoms which after taking history and clinical examinations seemed to be related to TMD. In the present study, the patients who were complaining of otalgia, ear fullness, tinnitus, hearing loss, and dizziness were evaluated by an ear fellow. Forty patients who had no known otologic or other primary causes to explain their symptoms, were referred to the orofacial pain clinic with the possible diagnosis of TMD. If the diagnosis was confirmed by an orofacial pain specialist, a combination of TMD treatments was administered to each case and the patients were followed up. The results showed that following implementation of treatment protocols for TMD, more than 50% of the patients reported complete or partial recovery in the second follow-up (p < 0.05). The most common otologic symptom of the referred cases was earache, and the most common associated complaint was neck pain. All the patients had one or more parafunctional habits. This study showed that TMD treatments were significantly efficient in improving otologic symptoms partially or completely and the authors concluded that for the patients with otolaryngologic unexplained symptoms, an overhaul examination is needed to assess TMD as a possible cause of the patient complaint. It is recommended that in cases with unexplained otologic symptoms, otolaryngologists care more about the neck trigger points (TP) and ask about the patient's parafunctional habits. Otolaryngologists and dentists need to be aware of the risk of developing otologic symptoms caused by these habits or cervical TPs.

Bioactive and Biodegradable Polycaprolactone-Based Nanocomposite for Bone Repair Applications.

This study investigated the relationship between the structure and mechanical properties of polycaprolactone (PCL) nanocomposites reinforced with baghdadite, a newly introduced bioactive agent. The baghdadite nanoparticles were synthesised using the sol-gel method and incorporated into PCL films using the solvent casting technique. The results showed that adding baghdadite to PCL improved the nanocomposites' tensile strength and elastic modulus, consistent with the results obtained from the prediction models of mechanical properties. The tensile strength increased from 16 to 21 MPa, and the elastic modulus enhanced from 149 to 194 MPa with fillers compared to test specimens without fillers. The thermal properties of the nanocomposites were also improved, with the degradation temperature increasing from 388 °C to 402 °C when 10% baghdadite was added to PCL. Furthermore, it was found that the nanocomposites containing baghdadite showed an apatite-like layer on their surfaces when exposed to simulated body solution (SBF) for 28 days, especially in the film containing 20% nanoparticles (PB20), which exhibited higher apatite density. The addition of baghdadite nanoparticles into pure PCL also improved the viability of MG63 cells, increasing the viability percentage on day five from 103 in PCL to 136 in PB20. Additionally, PB20 showed a favourable degradation rate in PBS solution, increasing mass loss from 2.63 to 4.08 per cent over four weeks. Overall, this study provides valuable insights into the structure-property relationships of biodegradable-bioactive nanocomposites, particularly those reinforced with new bioactive agents.

Expression analysis of genes involved in the expansion of hematopoietic stem cells (SCF, Flt3-L, TPO, IL-3, and IL-6) in unrestricted somatic stem cells cultured on fibrin.

Umbilical cord blood (UCB) transplantation is a promising therapeutic approach for patients lacking HLA-matched donors. A main limitation to the use of UCB-derived HSCs (UCB-HSCs) is the low number of transplantable cells. Novel culture strategies are being developed to increase the number of HSCs. Unrestricted somatic stem cells (USSCs) have been identified as promising stromal cells for supporting HSC expansion. The current study aimed to explore the effect of fibrin on the expression of hematopoiesis-related genes (SCF, Flt3-L, TPO, IL-3, and IL-6) in USSCs. USSCs were isolated from UCB and characterized by flow cytometry and in vitro multilineage differentiation ability. DAPI staining and the MTT assay were used to assess the effect of fibrin on USSC viability. The cell attachment was evaluated using SEM. qRT-PCR was performed to evaluate the expression of SCF, Flt3-L, TPO, IL-3, and IL-6 in USSCs cultured on 3D fibrin scaffolds. USSCs were positive for CD73, CD105, and CD166 and negative for CD45. Alizarin red and Oil red O stains confirmed calcium deposition and lipid vacuoles in USSCs. Results obtained from DAPI and MTT assays revealed a positive effect of fibrin on USSC viability. Cells cultured on fibrin express significantly higher levels of SCF and TPO compared to those grown in a 2D environment. The positive effect of fibrin on IL-6 levels was reversed. Fibrin did not affect Flt3-L expression and IL-3 mRNA expression was not detected in either group. The results of this study provide the basis for developing further research on the ex vivo expansion of HSCs with USSCs.

Comparison of pain catastrophizing and anxiety in patients with dyspareunia and healthy women: a cross-sectional study.

Despite the prominent role of cognitive-affective variables, such as pain catastrophizing and anxiety in chronic pain, little is known about their relationship with dyspareunia. This study compared pain-catastrophizing and anxiety in reproductive-aged women with and without dyspareunia. A controlled cross-sectional study was conducted on 398 married women in Iran selected by convenience sampling. Sampling was performed both online and in person. Data were collected using a checklist designed for the study, including background characteristics, self-reported dyspareunia, and two standard questionnaires: the Pain Catastrophizing Scale (PCS) and the Spielberger State-Trait Anxiety Inventory-6 (STAI-6). Results showed that 49.5% of the women reported dyspareunia in the previous six months, with a reduced figure of 42% and 31% when using more specific criteria for dyspareunia. Women with dyspareunia had significantly higher scores for pain catastrophizing and anxiety than the control group without dyspareunia. Pain-catastrophizing was associated with aversion to genital contact and body image dissatisfaction. Anxiety was correlated with age, marriage duration, and sexual abuse. Managing anxiety and catastrophizing thoughts may help dyspareunia patients better cope with pain.

Additive Manufacturing of 3D Anatomical Models-Review of Processes, Materials and Applications.

The methods of additive manufacturing of anatomical models are widely used in medical practice, including physician support, education and planning of treatment procedures. The aim of the review was to identify the area of additive manufacturing and the application of anatomical models, imitating both soft and hard tissue. The paper outlines the most commonly used methodologies, from medical imaging to obtaining a functional physical model. The materials used to imitate specific organs and tissues, and the related technologies used to produce, them are included. The study covers publications in English, published by the end of 2022 and included in the Scopus. The obtained results emphasise the growing popularity of the issue, especially in the areas related to the attempt to imitate soft tissues with the use of low-cost 3D printing and plastic casting techniques.

Knowledge, Skills, and Self-Disclosure Following a Sexual Abuse Prevention Program Among Iranian Preschoolers: A Cluster Quasi-Experimental Controlled Study.

Standard empirical studies are needed despite three decades of research on child sexual abuse prevention programs (CSAPPs). This study aimed to investigate the effects of CSAPP on the child's sexual safety. A multicenter, random cluster, quasi-experimental controlled survey was conducted in a 1:1 ratio in Tehran, Iran, from May to December 2019 in seventy 5- to 6-years-old children from 10 kindergartens. In groups of 7 to 8, the intervention group participated in four sessions of 45 minutes of face-to-face sexual self-care training, 3 to 4 days apart. The control groups received one session on accident safety. Knowledge, self-protective skills, fear, and self-disclosure were assessed respectively by the "Personal Safety Questionnaire (PSQ)," "What If Situation Test (WIST)," "Fear Assessment Thermometer Scale (FATS)," and researcher-made questions before and 8 weeks after the intervention. At the baseline, children obtained 70% of knowledge and 45% of protective skills scores. After the intervention, knowledge, protective skills, and detection of "appropriate requests" were significantly promoted (p < .001). Detecting "inappropriate requests" did not differ; however, all quadruple skills (Say, Do, Tell, and Report) improved significantly. "Girl sex" and "parents' education" were related factors promoting children's protective skills. Sexual abuse self-disclosure was 4.2% (n = 3), and one child reported child sexual abuse (CSA) only after the intervention. Despite the lack of formal education, children's basic knowledge reflects the importance of parents in preventing CSA. However, the CSAPP significantly improved children's skills and revealed one CSA case. CSAPP should not focus solely on risky scenarios because if children cannot distinguish between safe and unsafe situations, they will experience unnecessary anxiety. Even after recognizing the dangerous conditions, CSA prevention will practically fail without appropriate reactions such as escaping and reporting. CSAPP should emphasize individual rights such as body ownership and assertiveness skills and explain the "danger of known people" with detailed scenarios, especially in collectivistic and traditional societies.

Beneficial effects of celery seed extract (Apium graveolens), as a supplement, on anxiety and depression in hypertensive patients: a randomized clinical trial.

BACKGROUND: Anxiety and depression are crucial public health issues, affecting the rising in hospitalizations and death. Anxiety and depression can worsen hypertension and vice versa. OBJECTIVE: The current study has investigated the effects of celery seed extract, as a drug supplement, with the active ingredient of 3-n-butylphthalide, on mental problems primarily anxiety and secondary depression in hypertensive patients. DESIGN: The current study was a randomized, triple-blind, placebo-controlled, cross-over, 4-week clinical trial with a 4-week washout period. Fifty hypertensive patients received 4 placebo or celery seed extract capsules (1.34 g per day) for 4 weeks as a supplement to their usual medication regimen. The blood pressure parameters were assessed using 24-h ambulatory blood pressure monitoring device. Anxiety and depression and their wide range of symptoms were evaluated using Beck anxiety and depression inventories (BAI and BDI). RESULTS: In the celery treatment step, the mean reduction in BAI and BDI scores were 6.78 (P < 0.001) and 3.63 (P < 0.01), respectively. Some symptoms of anxiety including unable to relax, nervousness, numbness, dizziness, flushed face, sweating, and breathing difficulty were significantly improved by celery consumption (P < 0.001). Celery could decrease symptoms of depression such as sadness, crying, loss of energy, insomnia, irritability, fatigue, loss of interest in sex, and punishment feeling (P < 0.01). The mean reduction in blood pressure parameters was also significant during celery therapy (P < 0.001). CONCLUSIONS: The psychometric properties of anxiety and depression were investigated and the results were promising. The results indicated the anti-anxiety and anti-depressive properties of celery seed extract as a supplement in hypertensive patients. CLINICAL TRIAL REGISTRATION: Registry name: Iranian Registry of Clinical Trials (IRCT), Registration number: IRCT20130418013058N8, Registration link: https://www.irct.ir/trial/30021 . The study was carried out between 2018-09-21 and 2020-07-20.

In vitro release of silver ions and expression of osteogenic genes by MC3T3-E1 cell line cultured on nano-hydroxyapatite and silver/strontium-coated titanium plates.

Attempts are ongoing to improve the surface properties of dental implants by application of different coatings, aiming to enhance osseointegration, and decrease the adverse effects of titanium and its alloys used in dental implants. Coating of implant surface with hydroxyapatite (HA) is one suggested strategy for this purpose due to its high biocompatibility and similar structure to the adjacent bone. This study aimed to quantify the release of silver ions and expression of osteogenic genes by MC3T3-E1 cells cultured on nano-HA and silver/strontium (Ag/Sr)-coated titanium plates via the electrochemical deposition method. Plates measuring 10 × 10 × 0.9 mm were fabricated from Ti-6Al-4 V alloy, and polished with silicon carbide abrasive papers before electrochemical deposition to create a smooth, mirror-like surface. After applying homogenous nano-HA coatings with/without silver/strontium on the surface of the plates, the composition of coatings was confirmed by energy-dispersive X-ray spectroscopy (EDS), and their morphological properties were analyzed by scanning electron microscopy (SEM). The coated specimens were then immersed in simulated body fluid (SBF), and the concentration of released sliver ions was quantified by spectroscopy at 7-14 days. The MC3T3-E1 osteoblastic cell line was cultured in osteogenic medium for 7-14 days, and after RNA extraction and cDNA synthesis, the expression of runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN); osteogenic genes was quantified by polymerase chain reaction (PCR) using SYBR Green Master Mix kit. The expression of genes and the released amount of silver ions were compared between the two groups using the Mann-Whitney U test. The two groups were not significantly different regarding silver ion release at 14 days (P > 0.05). However, silver ion release was significantly higher from nano-HA coatings with silver/strontium at 7 days (P = 0.03). The difference in expression of RUNX2 (P = 0.04), OPN (P = 0.04), and OCN (P = 0.03) genes was also significant between nano-HA coating groups with and without silver/strontium at 7 days, and the expressions were higher in nano-HA with silver/strontium group, but this difference was not significant at 14 days. Addition of silver and strontium to specimens coated with nano-HA increased the release of silver ions within the non-toxic range, and enhanced the expression of osteogenic genes particularly after 7 days.

Purine Nucleoside Phosphorylase Deficiency in Two Unrelated Patients with Autoimmune Hemolytic Anemia and Eosinophilia: Two Novel Mutations.

Two Iranian patients with purine nucleoside phosphorylase (PNP) deficiency are described in terms of their clinical and molecular evaluations. PNP deficiency is a rare form of combined immunodeficiency with a profound cellular defect. Patients with PNP deficiency suffer from variable recurrent infections, hypouricemia, and neurological manifestations. Furthermore, patient 1 developed mild cortical atrophy, and patient 2 presented developmental delay, general muscular hypotonia, and food allergy. The two unrelated patients with developed autoimmune hemolytic anemia and T cells lymphopenia and eosinophilia were referred to Immunology, Asthma and Allergy Research Institute (IAARI) in 2019. After taking blood and DNA extraction, genetic analysis of patient 1 was performed by PCR and direct sequencing and whole exome sequencing was applied for patient 2 and the result was confirmed by direct sequencing in the patient and his parents. The genetic result showed two novel variants in exon 3 (c.246_285+9del) and exon 5 (c.569G>T) PNP (NM_000270.4) in the patients, respectively. These variants are considered likely pathogenic based on the American College of Medical Genetics and Genomics (ACMG) guideline. PNP deficiency has a poor prognosis; therefore, early diagnosis would be vital to receive hematopoietic stem cell transplantation (HSCT) as a prominent and successful treatment.

Comparison of Periodontal Ligament Stem Cells with Mesenchymal Stem Cells from Other Sources: A Scoping Systematic Review of In vitro and In vivo Studies.

OBJECTIVE: The application of stem cells in regenerative medicine depends on their biological properties. This scoping review aimed to compare the features of periodontal ligament stem cells (PDLSSCs) with stem cells derived from other sources. DESIGN: An electronic search in PubMed/Medline, Embase, Scopus, Google Scholar and Science Direct was conducted to identify in vitro and in vivo studies limited to English language. RESULTS: Overall, 65 articles were included. Most comparisons were made between bone marrow stem cells (BMSCs) and PDLSCs. BMSCs were found to have lower proliferation and higher osteogenesis potential in vitro and in vivo than PDLSCs; on the contrary, dental follicle stem cells and umbilical cord mesenchymal stem cells (UCMSCs) had a higher proliferative ability and lower osteogenesis than PDLSCs. Moreover, UCMSCs exhibited a higher apoptotic rate, hTERT expression, and relative telomerase length. The immunomodulatory function of adipose-derived stem cells and BMSCs was comparable to PDLSCs. Gingival mesenchymal stem cells showed less sensitivity to long-term culture. Both pure and mixed gingival cells had lower osteogenic ability compared to PDLSCs. Comparison of dental pulp stem cells (DPSCs) with PDLSCs regarding proliferation rate, osteo/adipogenesis, and immunomodulatory properties was contradictory; however, in vivo bone formation of DPSCs seemed to be lower than PDLSCs. CONCLUSION: In light of the performed comparative studies, PDLSCs showed comparable results to stem cells derived from other sources; however, further in vivo studies are needed to determine the actual pros and cons of stem cells in comparison to each other.

Growth Factors in Periodontal Complex Regeneration.

The ultimate goal of periodontal treatments is the regeneration of all lost periodontal tissues including bone, cementum and the periodontal ligament (PDL). Until now, the clinical methods for periodontal regeneration have been associated with significant failure or incomplete success. Various studies have reported the promising effects of growth factors/cytokines on periodontal regeneration. Growth factors/cytokines include proteins or steroid hormones that bind to cellular receptors, known as signalling molecules, and that trigger cellular responses that eventually stimulate cell proliferation and differentiation. The present review aims to provide an overview of the main growth factors that play an important role in and have been used in the regeneration of periodontal components.

Effect of celery (Apium graveolens) seed extract on hypertension: A randomized, triple-blind, placebo-controlled, cross-over, clinical trial.

In the present work, the antihypertensive effects of celery seed extract (Apium graveolens) with active ingredients, such as 3-n-butylphthalide, were studied as a drug supplement in the treatment of hypertension. This study was a randomized, triple-blind, placebo-controlled, cross-over clinical trial. Fifty-two patients were divided into two groups (celery and placebo) and completed the two-step clinical trial. Four celery seed extract capsules (totally 1.34 g per day) or 4 placebo capsules per day were administered to the patients during a 4-week clinical trial. The blood pressure was assessed using a 24-hr ambulatory blood pressure monitoring method. In celery group, systolic blood pressure changed from 141.2 ± 5.91 to 130.0 ± 4.38 mmHg (p < .001) while diastolic blood pressure changed from 92.2 ± 5.74 to 84.2 ± 4.87 mmHg (p < .001). Moreover, the mean arterial blood pressure changed from 108.5 ± 5.76 to 99.5 ± 4.66 mmHg (p < .001), and pulse pressure decreased from 49.0 ± 6.21 to 45.8 ± 6.01 mmHg (p < .01). However, no significant changes were observed in placebo group in terms of the above-mentioned parameters (p > .05). Furthermore, no significant side effect was reported in the celery group, compared to the placebo group (p > .05). The results were promising and indicated the therapeutic effects of celery seed extract as a supplement in the management of hypertension.

Safety evaluation and biochemical efficacy of celery seed extract (Apium Graveolens) capsules in hypertensive patients: a randomized, triple-blind, placebo-controlled, cross-over, clinical trial.

The present study was conducted to evaluate the safety of celery seed extract (Apium graveolens), as a medicinal herb with active ingredients such as 3-n-butylphthalide (NBP), in hypertensive patients. This study was a randomized, triple-blind, placebo-controlled, cross-over clinical trial. Hypertensive patients (51 participants) received 4 celery seed capsules (a total of 1.34 g extract per day) or 4 placebo capsules per day for 4 weeks as a supplement to their usual medication regimen. The results indicated that the celery seed capsule not only was safe for hypertensive patients but also caused a reduction in BP, FBS, and lipid profile values. Also, it had beneficial effects on kidney and liver functions. No significant change was observed in blood cells and serum electrolytes (p > 0.05). The mean reduction in BUN and SCr were 3.43 and 0.075 mg/dL, and in SGPT and SGOT were 4.08 and 3.03 U/L, respectively (p < 0.05). FBS reduced from 108.53 to 97.96 mg/dL after 4 weeks of celery administration (p < 0.01). The decrease in TC, TG, LDL, and increase in HDL were 16.37, 16.22, 11.84, and 2.52 mg/dL, respectively (p < 0.001). According to the promising results of this clinical trial, celery seed extract can be considered a safe supplement for hypertensive patients. The study is limited by the small sample size; therefore, larger randomized trials are required.

3D Printed Composite Scaffolds in Bone Tissue Engineering: A Systematic Review.

OBJECTIVE: This study aimed to analyze the effect of fabrication factors on both biological and physico-chemical features of 3-dimensional (3D) printed composite scaffolds. METHOD: Electronic search was done according to the PRISMA guideline in PubMed and Scopus databases limited to English articles published until May 2021. Studies in which composite scaffolds were fabricated through computer-aided design and computer-aided manufacturing (CADCAM)- based methods were included. Articles regarding the features of the scaffolds fabricated through indirect techniques were excluded. RESULTS: Full text of 121 studies were reviewed, and 69 met the inclusion criteria. According to analyzed studies, PCL and HA were the most commonly used polymer and ceramic, respectively. Besides, the solvent-based technique was the most commonly used composition technique, which enabled preparing blends with high concentrations of ceramic materials. The most common fabrication method used in the included studies was Fused Deposition Modeling (FDM). The addition of bio-ceramics enhanced the mechanical features and the biological behaviors of the printed scaffolds in a ratio-dependent manner. However, studies that analyzed the effect of ceramic weight ratio showed that scaffolds with the highest ceramic content did not necessarily possess the optimal biological and non-biological features. CONCLUSION: The biological and physico-chemical behaviors of the scaffold can be affected by pre-printing factors, including utilized materials, composition techniques, and fabrication methods. Fabricating scaffolds with high mineral content as of the natural bone may not provide the optimal condition for bone formation. Therefore, it is recommended that future studies compare the efficiency of different kinds of biomaterials rather than different weight ratios of one type.

Developing Novel Fabrication and Optimisation Strategies on Aggregation-Induced Emission Nanoprobe/Polyvinyl Alcohol Hydrogels for Bio-Applications.

The current study describes a new technology, effective for readily preparing a fluorescent (FL) nanoprobe-based on hyperbranched polymer (HB) and aggregation-induced emission (AIE) fluorogen with high brightness to ultimately develop FL hydrogels. We prepared the AIE nanoprobe using a microfluidic platform to mix hyperbranched polymers (HB, generations 2, 3, and 4) with AIE (TPE-2BA) under shear stress and different rotation speeds (0-5 K RPM) and explored the FL properties of the AIE nanoprobe. Our results reveal that the use of HB generation 4 exhibits 30-times higher FL intensity compared to the AIE alone and is significantly brighter and more stable compared to those that are prepared using HB generations 3 and 2. In contrast to traditional methods, which are expensive and time-consuming and involve polymerization and post-functionalization to develop FL hyperbranched molecules, our proposed method offers a one-step method to prepare an AIE-HB nanoprobe with excellent FL characteristics. We employed the nanoprobe to fabricate fluorescent injectable bioadhesive gel and a hydrogel microchip based on polyvinyl alcohol (PVA). The addition of borax (50 mM) to the PVA + AIE nanoprobe results in the development of an injectable bioadhesive fluorescent gel with the ability to control AIEgen release for 300 min. When borax concentration increases two times (100 mM), the adhesion stress is more than two times bigger (7.1 mN/mm2) compared to that of gel alone (3.4 mN/mm2). Excellent dimensional stability and cell viability of the fluorescent microchip, along with its enhanced mechanical properties, proposes its potential applications in mechanobiology and understanding the impact of microstructure in cell studies.

Prefabrication technique by preserving a muscular pedicle from masseter muscle as an in vivo bioreactor for reconstruction of mandibular critical-sized bone defects in canine models.

In vivo bioreactors serve as regenerative niches that improve vascularization and regeneration of bone grafts. This study has evaluated the masseter muscle as a natural bioreactor for ßTCP or PCL/ßTCP scaffolds, in terms of bone regeneration. The effect of pedicle preservation, along with sole, or MSC- or rhBMP2-combined application of scaffolds, has also been studied. Twenty-four mongrel dogs were randomly placed in six groups, including ßTCP, ßTCP/rhBMP2, ßTCP/MSCs, PCL/ßTCP, PCL/ßTCP/rhBMP2, and PCL/ßTCP/MSCs. During the first surgery, the scaffolds were implanted into the masseter muscle for being prefabricated. After 2 months, each group was divided into two subgroups prior to mandibular bone defect reconstruction; one with a preserved vascularized pedicle and one without. After 12 weeks, animals were euthanized, and new bone formation was evaluated using histological analysis. Histological analysis showed that all ß-TCP scaffold groups had resulted in significantly greater rates of new bone formation, either with a pedicle surgical approach or non-pedicle surgical approach, comparing to their parallel groups of ßTCP/PCL scaffolds (p ≤ .05). Pedicled ß-TCP scaffold groups that were treated with either rhBMP2 (48.443% ± 0.250%) or MSCs (46.577% ± 0.601%) demonstrated the highest rates of new bone formation (p ≤ .05). Therefore, masseter muscle can be used as a local in vivo bioreactor with potential clinical advantages in reconstruction of human mandibular defects. In addition, scaffold composition, pedicle preservation, and treatment with MSCs or rhBMP2, influence new bone formation and scaffold degradation rates in the prefabrication technique.