Acemannan coated, cobalt-doped biphasic calcium phosphate nanoparticles for immunomodulation regulated bone regeneration.

Biomaterials are used as scaffolds in bone regeneration to facilitate the restoration of bone tissues. The local immune microenvironment affects bone repair but the role of immune response in biomaterial-facilitated osteogenesis has been largely overlooked and it presents a major knowledge gap in the field. Nanomaterials that can modulate M1 to M2 macrophage polarization and, thus, promote bone repair are known. This study investigates a novel approach to accelerate bone healing by using acemannan coated, cobalt-doped biphasic calcium phosphate nanoparticles to promote osteogenesis and modulate macrophage polarization to provide a prohealing microenvironment for bone regeneration. Different concentrations of cobalt were doped in biphasic calcium phosphate nanoparticles, which were further coated with acemannan polymer and characterized. The nanoparticles showed >90% cell viability and enhanced cell proliferation along with osteogenic differentiation as demonstrated by the enhanced alkaline phosphatase activity and osteogenic calcium deposition. The morphology of MC3T3-E1 cells remained unchanged even after treatment with nanoparticles. Acemannan coated nanoparticles were also able to decrease the expression of M1 markers, iNOS, and CD68 and enhance the expression of M2 markers, CD206, CD163, and Arg-1 as indicated by RT-qPCR, flow cytometry, and ICC studies. The findings show that acemannan coated nanoparticles can create a supportive immune milieu by inducing and promoting the release of osteogenic markers, and by causing a reduction in inflammatory markers, thus helping in efficient bone regeneration. As per our knowledge, this is the first study showing the combined effect of acemannan and cobalt for bone regeneration using immunomodulation. The work presents a novel approach for enhancing osteogenesis and macrophage polarization, thus, offering a potent strategy for effective bone regeneration.

Investigating the Role of Amino Acids in Short Peptides for Hydroxyapatite Binding and Osteogenic Differentiation of Mesenchymal Stem Cells to Aid Bone Regeneration.

Bone defects show a slow rate of osteoconduction and imperfect reconstruction, and the current treatment strategies to treat bone defects suffer from limitations like immunogenicity, lack of cell adhesion, and the absence of osteogenic activity. In this context, bioactive supramolecular peptides and peptide gels offer unique opportunities to develop biomaterials that can play a dominant role in the biomineralization of bone tissues and promote bone formation. In this article, we have demonstrated the potential of six tetrapeptides for specific binding to hydroxyapatite (HAp), a major inorganic component of the bone, and their effect on the growth and osteogenic differentiation of mesenchymal stem cells (MSCs). We adopted a simplistic approach of rationally designing amphiphilic peptides by incorporating amino acids, Ser, pSer, Pro, Hyp, Asp, and Glu, which are present in either collagenous or noncollagenous proteins and render properties like antioxidant, calcification, and mineralization. A total of six tetrapeptides, Trp-Trp-His-Ser (WWHS), Trp-Trp-His-pSer (WWHJ), Trp-Trp-His-Pro (WWHP), Trp-Trp-His-Hyp (WWHO), Trp-Trp-His-Asp (WWHD), and Trp-Trp-His-Glu (WWHE), were synthesized. Four peptides were found to self-assemble into nanofibrillar gels resembling the extracellular matrix (ECM), and the remaining two peptides (WWHJ, WWHP) self-assembled into nanorods. The peptides showed excellent cell adhesion, encapsulation, proliferation, and migration and induced the differentiation of mesenchymal stem cells (MSCs), as evident from the enhanced mineralization, resulting from the upregulation of osteogenic markers, RUNX 2, COL I, OPN, and OCN, alkaline phosphatase (ALP) production, and calcium deposition. The peptides also induced the downregulation of inflammatory markers, TNF-α and iNOS, and the upregulation of the anti-inflammatory marker, IL-10, resulting in M2 macrophage polarization. RANKL and TRAP genes were downregulated in a coculture system of MC3T3-E1 and RAW 264.7 cells, implying that peptides promote osteogenesis and inhibit osteoclastogenesis. The peptide-based biomaterials developed in this work can enhance bone regeneration capacity and show strong potential as scaffolds for bone tissue engineering.

Thiol-Functionalized, Antioxidant, and Osteogenic Mesoporous Silica Nanoparticles for Osteoporosis.

Osteoporosis is a chronic bone disorder characterized by decreased bone mass, leading to brittle bones and fractures. Oxidative stress has been identified as the most profound trigger for the initiation and progression of osteoporosis. Current treatment strategies do not induce new bone formation and fail to address a high level of reactive oxygen species (ROS). Mesoporous silica nanoparticles (MSNs) have been explored in bone tissue regeneration owing to their inherent osteogenic property, but they lack antioxidant and cell adhesion properties, required in such applications. We have developed thiolated, bioactive mesoporous silica nanoparticles (MSN-SH) to address this challenge. MSNs were fabricated using the Stöber method, and 11% of the surface was functionalized post-synthesis with thiol groups using MPTMS to obtain MSN-SH. The particle size measured by the dynamic light scattering technique was found to be around 300 nm. The surface morphology was investigated using HR-TEM, and their physical and chemical properties were characterized using various spectroscopic techniques. They exhibited more than 90% antioxidant activity, neutralized ROS formed in cells, and provided protection against ROS-induced cell damage. The cell viability assay in murine osteoblast precursor cells (MC3T3) showed that MSN-SH is cell-proliferative in nature with 140% cell viability. Osteogenic potential was evaluated by measuring the ALP activities, calcium deposition, and gene expression levels of osteogenic markers, such as RUNX2, ALP, OCN, and OPN, and results revealed that MSN-SH increases calcium deposition and induces osteogenesis through upregulation of osteogenic genes and markers without the involvement of any osteogenic supplements. Besides promoting osteogenesis, MSN-SH was found to inhibit osteoclastogenesis. The nanomaterial was found to be regenerative in nature, and it stimulated migration of osteoblast cells and caused a complete wound closure within 48 h. We were able to achieve a multifunctional nanomaterial by simply modifying the surface. MSNs have been explored for bone tissue engineering/osteoporosis as a composite system incorporating metals, like gold and cerium, or as a nanocarrier loaded with growth factors or active drugs. This study offers a simple and economical method to enhance the existing properties of MSNs and impart new activities by a single-step surface modification. It can be concluded that MSN-SH holds promise as a complementary and alternate treatment for osteoporosis along with the standardized therapy.

Effectiveness of multistimulation approach on feeding habits of low-birth-weight babies-A randomized control trial.

Introduction: Low- birth- weight neonates face oral feeding difficulties due to hemodynamic instability, immaturity of central nervous systems, and incomplete development of oral functions. Use of several interventions might help in improvement of the feeding ability of neonates. The objective of the study was to evaluate the effect of the multistimulation approach in low-birth-weight babies on the oral feeding performance, oral intake volume, weight gain and transition time from tube to total oral intake. Methods: A Randomized, parallel-group, multiple arm trial study was conducted, and a total of 44 low birth weight babies were randomized into three parallel groups with a 2:1:1 ratio. Babies who are Hemodynamically stable were included in the trial. In two Intervention groups, one received an oral stimulation program, another intervention group received tactile stimulation, and the control group received routine newborn procedures for the same duration of time. Oral feeding performance was determined by Oral Feeding Skills (OFS) on a daily basis for five days after providing ten days of intervention. Neonates were monitored until hospital discharge. Results: Infants in the stimulation groups had significantly better oral feeding performance than infants in the control group in terms of mean proficiency, transfer rate and overall transfer of feeding volume. There was a substantial increase in mean feeding score, daily weight, oral intake volume, and early transition time in both intervention groups compared to control. There was no significant difference in feeding behaviours between the oromotor and multistimulation groups, but the multistimulation group gained more weight compared to the oromotor group. Conclusions: Infants exposed to the stimulation programme had better feeding skills and a shorter transition period from tube feeding to oral feeding; however, the babies who received multistimulation gained greater weight than babies who received only oromotor stimulation. The study recommends multi stimulation in the form of oromotor, and tactile stimulation can be used as an effective NICU procedure for maintaining an infant's ability to take feeds orally before being discharged from the hospital.

Cisplatin and Probiotic Biomass Loaded Pessaries for the Management of Cervical Cancer.

INTRODUCTION: Cancer is a type of disease, in which the growth of cells is abnormal and uncontrolled. One of the most common cancers among women is cervical cancer. In India, cervical cancer is one of leading causes of cancer mortality among women 30 to 69 years of age, accounting for 17% of all cancer deaths. The work present here shows the combined effects of anticancer drug along with probiotics to circumvent the side effects associated with chemotherapy and to enhance the therapeutic effect. MATERIALS AND METHODS: Cisplatin and drug loaded pessaries were prepared by melt mold method using the blend of PEG's (Polyethylene Glycol) and further characterized for various in vitro and in vivo parameters. RESULTS AND DISCUSSION: The free radical scavenging activity of probiotic Lactobacillus rhamnosus by DPPH (2,2-diphenyl-1-picrylhydrazyl) assay was observed to be 60.77µg/mL The mean weight variation, melting time, content uniformity, friability and hardness of the prepared pessary were 1.25±0.025mg, 10.86±0.64min, 99.89±0.74, 0.25%, 2.2kg/cm2. Histopathology studies presented that the developed formulation are safe for local delivery of cisplatin. CONCLUSION: This study provides the basis for a combination of local delivery approach along with the beneficial effects of probiotic strain which could be better a approach for the treatment of cervical cancer.

Quality of life in children managed for extrahepatic portal venous obstruction.

OBJECTIVES: There are no studies on health-related quality of life (HRQOL) in children with extrahepatic portal venous obstruction (EHPVO). The present study evaluated the QOL in children with EHPVO, prevariceal and postvariceal esophageal variceal eradication, and postsurgery in comparison with healthy controls. METHODS: Children with EHPVO and variceal bleeding were divided into 3 groups: group A, before variceal eradication (n = 50); group B, after variceal eradication (n = 50); and group C, after surgery (n = 12). Group D comprised healthy children (n = 50). Clinical details and investigations were recorded. The Pediatric Quality of Life Inventory parent-proxy HRQOL questionnaire was used for assessment of QOL. RESULTS: Compared with controls, patients with EHPVO in groups A, B, and C had lower median QOL scores in physical, emotional, social, and school functioning health domains. Esophageal variceal eradication had no significant effect on QOL (median total QOL score pre- and postvariceal eradication of 87.5 vs 86.3). Increasing size of spleen (mild 92.5, moderate 88.2, and severe 76.2; P < 0.001), presence of hypersplenism (90 vs 73.7, P = 0.001), and growth retardation (90 vs 82.5, P = 0.04) caused significant reduction of the total QOL score. On multivariate regression analysis, splenic size and growth retardation were found to be independent predictors that affect the QOL. After surgery, a trend toward improvement in physical, psychosocial, and total QOL scores was present, but it was not significant. CONCLUSIONS: Children with EHPVO have a poor QOL that is not affected by variceal eradication. Splenomegaly and growth retardation significantly affect the HRQOL. A trend toward improvement of QOL scores is observed in the postsurgery group.