Understanding Matrix Stiffness in Vinyl Polymer Hydrogels: Implications in Bone Tissue Engineering.

Matrix elasticity helps to direct bone cell differentiation, impact healing processes, and modify extracellular matrix deposition, all of which are required for tissue growth and maintenance. In this work, we evaluated the role of inorganic nanocrystals or mineral inducers such as nanohydroxyapatite, alkaline phosphatase, and nanoclay also known as montmorillonite deposited on vinyl-based hydrogels in generating matrices with different stiffness and their role in cell differentiation. Poly-2-(dimethylamino)ethyl methacrylate (PD) and poly-2-hydroxypropylmethacrylamide (PH) are the two types of vinyl polymers chosen for preparing hydrogels via thermal cross-linking. The hydrogels exhibited porosity, which decreased with an increase in stiffness. Each of the compositions is non-cytotoxic and maintains the viability of pre-osteoblasts (MC3T3-E1) and human bone marrow mesenchymal stem cells (hBMSCs). The PD hydrogels in the presence of ALP showed the highest mineralization ability confirmed through the alizarin assay and a better structural environment for their use as scaffolds for tissue engineering. The study reveals that understanding such interactions can generate hydrogels that can serve as efficient 3D models to study biomineralization.

Surface Engineered Osteoblast-Extracellular Vesicles Serve as an Efficient Carrier for Drug and Small RNA to Actively Target Osteosarcoma.

Osteosarcoma (OS) is a rare malignant tumor that affects soft tissue and has high rates of lung metastasis and mortality. The primary treatments for OS include preoperative chemotherapy, surgical resection of the lesion, and postoperative chemotherapy. However, OS chemotherapy presents critical challenges related to treatment toxicity and multiple drug resistance. To address these challenges, nanotechnology has developed nanosystems that release drugs directly to OS cells, reducing the drug's toxicity. Extracellular vesicles (EVs) are nanosized lipid-bilayer bound vesicles that act as cell-derived vehicles and drug delivery systems for several cancers. This study aims to utilize EVs for OS management by co-delivering Hdac1 siRNA and zoledronic acid (zol). The EVs' surface is modified with folic acid (FA) and their targeting ability is compared to that of native EVs. The results showed that the EVs' targeting ability depends on the parent cell source, and FA conjugation further enhanced it. Furthermore, EVs were used as the carrier for co-loading drug (zol) and small RNA (Hdac-1). This approach of using surface engineered EVs as carriers for cargo loading and delivery can be a promising strategy for osteosarcoma management.

Polymeric Nanoformulation of Zoledronic Acid Rescues Osteoblasts from the Harmful Effect of its Native Form: An In Vitro Investigation of Cytotoxic Potential on Osteoblasts and Osteosarcoma Cells.

Osteosarcoma (OS) is a malignant tumor, fatal for pediatric patients who do not respond to chemotherapy, alternative therapies and drugs can provide better outcomes. Zoledronic acid (Zol) belonging to the class of bisphosphonates (BPs) has a direct antitumor ability to prevent Ras GTPases modification and stimulate apoptosis. Despite advances in maintaining balance in skeletal events and direct anticancer properties, Zol causes cytotoxicity to normal healthy pre-osteoblast cells, hampering mineralization and differentiation. The study reports the preparation and evaluation of a nanoformulation that can diminish the existing drawbacks of native Zol. The cytotoxic effect is evaluated on bone cancer cells and healthy bone cells with three different cell lines namely, K7M2 (mouse OS cell line), SaOS2 (human OS cell line), and MC3T3E1 (healthy cell counterpart). It is observed that Zol nanoformulation is uptaken more (95%) in K7M2 whereas in MC3T3E1, the percent population internalizing nanoparticles (NPs) is 45%. Zol has a sustained release of 15% after 96 h from the NP which leads to a rescuing effect on the normal pre-osteoblast cells. In conclusion, it can be stated that Zol nanoformulation can be used as a good platform for a sustained release system with minimum side effects to normal bone cells.

The role of polyplexes in developing a green sustainable approach in agriculture.

Rise in global population has increased the food demands and thus the competition among farmers to produce more and more. In the race to obtain higher productivity, farmers have resorted to injudicious farming practices that include the reckless use of nitrogenous fertilizers and intensive cropping on farmlands. Such practices have paved the path for large scale infestations of crops and plants by pests thus affecting the plant productivity and crop vigour. There are several traditional techniques to control pest infestations in plants such as the use of chemical or bio-pesticides, and integrated pest management practices which face several drawbacks. Delivery of gene/nucleic acid in plants through genetic engineering approaches is a more sustainable and effective method of protection against pests. The technology of RNA interference (RNAi) provides a sustainable solution to counter pest control problems faced by other traditional techniques. The RNAi technique involves delivery of dsDNA/dsRNA or other forms of nucleic acids into target organisms thereby bringing about gene silencing. However, RNAi is also limited to its use because of their susceptibility to degradation wherein the use of cationic polymers can provide a tangible solution. Cationic polymers form stable complexes with the nucleic acids known as "polyplexes", which may be attributed to their high positive charge densities thus protecting the exogenous nucleic acids from extracellular degradation. The current paper focuses on the utility of nucleic acids as a sustainable tool for pest control in crops and the use of cationic polymers for the efficient delivery of nucleic acids in pests thus protecting the plant from infestations.