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Osteochondral tissue is a highly specialized and complex tissue composed of articular cartilage and subchondral bone that are separated by a calcified cartilage interface. Multilayered or gradient scaffolds, often in conjunction with stem cells and growth factors, have been developed to mimic the respective layers for osteochondral defect repair. In this study, we designed a hyaline cartilage-hypertrophic cartilage bilayer graft (RGD/RGDW) with chondrocytes. Previously, we demonstrated that RGD peptide-modified chondroitin sulfate cryogel (RGD group) is chondro-conductive and capable of hyaline cartilage formation. Here, we incorporated whitlockite (WH), a Mg 2+ -containing calcium phosphate, into RGD cryogel (RGDW group) to induce chondrocyte hypertrophy and form collagen X-rich hypertrophic cartilage. This is the first study to use WH to produce hypertrophic cartilage. Chondrocytes-laden RGDW cryogel exhibited significantly upregulated expression of hypertrophy markers in vitro and formed ectopic hypertrophic cartilage in vivo , which mineralized into calcified cartilage in bone microenvironment. Subsequently, RGD cryogel and RGDW cryogel were combined into bilayer (RGD/RGDW group) and implanted into rabbit osteochondral defect, where RGD layer supports hyaline cartilage regeneration and bioceramic-containing RGDW layer promotes calcified cartilage formation. While the RGD group (monolayer) formed hyaline-like neotissue that extends into the subchondral bone, the RGD/RGDW group (bilayer) regenerated hyaline cartilage tissue confined to its respective layer and promoted osseointegration for integrative defect repair., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The increase in plastic products and disposal poses a severe environmental challenge because of their poor biodegradability and undesirable disposal by landfilling. Recycling is the best possible solution to the environmental challenges implemented by the plastic industry. Pyrolysis is a process that converts waste plastics into pyrolytic oil, and it can be used as fuel in a blended form. The viscosity and lubricity of the LDWP (low-density waste polyethylene) pyrolytic oil were lower than standard diesel. Capparis spinosa methyl ester (CME) is blended and experimented with to overcome the lubricity issue of pyrolytic oil. In this investigation, 5%, 10%, and 15% CME were blended with PD20 (20% LDWP oil + 80% diesel) blend on a volume basis. Experiments were conducted to examine the effects of CME on combustion, performance, and emissions using the combination of CME and PD20 blend tested at 0%, 25%, 50%, 75%, and 100% loading conditions. All three ternary mixtures showed enhanced combustion performance and increased NO x and smoke emissions. Due to better combustion, the efficiency of the blend PCD10 (10% CME + 20% LDWP oil + 70% diesel) was higher than the PD20 blend and significantly closer to diesel. Hence, PCD10 is suggested as an alternative to diesel fuel., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The cranial sutures are proposed to be a stem cell niche, harbouring skeletal stem cells that are directly involved in development, homeostasis and healing. Like the craniofacial bones, the sutures are formed from both mesoderm and neural crest. During cranial bone repair, neural crest cells have been proposed to be key players; however, neural crest contributions to adult sutures are not well defined, and the relative importance of suture proximity is unclear. Here, we use genetic approaches to re-examine the neural crest-mesoderm boundaries in the adult mouse skull. These are combined with calvarial wounding experiments suggesting that suture proximity improves the efficiency of cranial repair. Furthermore, we demonstrate that Gli1+ and Axin2+ skeletal stem cells are present in all calvarial sutures examined. We propose that the position of the defect determines the availability of neural crest-derived progenitors, which appear to be a key element in the repair of calvarial defects., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

The field of tissue engineering and regenerative medicine has been evolving at a rapid pace with numerous novel and interesting biomaterials being reported. Hydrogels have come a long way in this regard and have been proven to be an excellent choice for tissue regeneration. This could be due to their innate properties such as water retention, and ability to carry and deliver a multitude of therapeutic and regenerative elements to aid in better outcomes. Over the past few decades, hydrogels have been developed into an active and attractive system that can respond to various stimuli, thereby presenting a wider control over the delivery of the therapeutic agents to the intended site in a spatiotemporal manner. Researchers have developed hydrogels that respond dynamically to a multitude of external as well as internal stimuli such as mechanics, thermal energy, light, electric field, ultrasonics, tissue pH, and enzyme levels, to name a few. This review gives a brief overview of the recent developments in such hydrogel systems which respond dynamically to various stimuli, some of the interesting fabrication strategies, and their application in cardiac, bone, and neural tissue engineering.

Gene therapy is a promising approach for the treatment of many diseases. However, the effective delivery of the cargo without degradation in vivo is one of the major hurdles. With the advent of lipid nanoparticles (LNPs) and cell-derived nanovesicles (CDNs), gene delivery holds a very promising future. The targeting of these nanosystems is a prerequisite for effective transfection with minimal side-effects. In this review, we highlight the emerging strategies utilized for the effective targeting of LNPs and CDNs, and we summarize the preparation methodologies for LNPs and CDNs. We have also highlighted the non-ligand targeting of LNPs toward certain organs based on their composition. It is highly expected that continuing the developments in the targeting approaches of LNPs and CDNs for the delivery system will further promote them in clinical translation., Competing Interests: The authors declare that they have no conflict of interests., (This journal is © The Royal Society of Chemistry.)

Sensing the mechanical properties of the substrates or the matrix by the cells and the tissues, the subsequent downstream responses at the cellular, nuclear and epigenetic levels and the outcomes are beginning to get unraveled more recently. There have been various instances where researchers have established the underlying connection between the cellular mechanosignalling pathways and cellular physiology, cellular differentiation, and also tissue pathology. It has been now accepted that mechanosignalling, alone or in combination with classical pathways, could play a significant role in fate determination, development, and organization of cells and tissues. Furthermore, as mechanobiology is gaining traction, so do the various techniques to ponder and gain insights into the still unraveled pathways. This review would briefly discuss some of the interesting works wherein it has been shown that specific alteration of the mechanical properties of the substrates would lead to fate determination of stem cells into various differentiated cells such as osteoblasts, adipocytes, tenocytes, cardiomyocytes, and neurons, and how these properties are being utilized for the development of organoids. This review would also cover various techniques that have been developed and employed to explore the effects of mechanosignalling, including imaging of mechanosensing proteins, atomic force microscopy (AFM), quartz crystal microbalance with dissipation measurements (QCMD), traction force microscopy (TFM), microdevice arrays, Spatio-temporal image analysis, optical tweezer force measurements, mechanoscanning ion conductance microscopy (mSICM), acoustofluidic interferometric device (AID) and so forth. This review would provide insights to the researchers who work on exploiting various mechanical properties of substrates to control the cellular and tissue functions for tissue engineering and regenerative applications, and also will shed light on the advancements of various techniques that could be utilized to unravel the unknown in the field of cellular mechanobiology., (© 2023. The Author(s).)

The therapeutics for bone tissue regeneration requires constant advancements owing to the steady increase in the number of patients suffering from bone-related disorders, and also to find efficient and cost-effective treatment modalities. One of the major advancements in the field of therapeutics is the development of mRNAs. mRNAs, which have been extensively tested for the vaccines, could be very well utilized as a potential inducer for bone regeneration. The ability of mRNAs to enter the cells and instruct the cellular machinery to produce the required native proteins such as BMP or VEGF is a great way to avoid the issues faced with growth factor deliveries such as the production cost, loss of biological function etc. However, there have been a few hurdles for using mRNAs as an effective therapeutic agent, such as proper dosing, tolerating the degradation by RNases, improving the half-life, controlling the spatio-temporal release and reducing the off-target effects. This brief review discusses the various developments in the field of mRNA therapeutics especially for bone tissue engineering, how nano-formulations are being developed to effectively deliver the mRNAs into the cells by evading the immune responses, how researchers have developed certain strategies to increase the half-life, to successfully deliver the mRNAs to specific bone defect area and bring about effective bone regeneration., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Calcium-based injectable hydrogels with various bioactive active molecules possess a great potential for bone regeneration. Herein, we have synthesized a chitin-PLGA-calcium sulfate hydrogel (CSG) containing bioactive molecules - lactoferrin (LF) and substance P (SP). SEM and XRD analysis revealed that CS crystal growth was altered with the addition of LF. Rheological measurements indicated that the injectability of the hydrogels was maintained after the addition of LF, however, there was a reduction in storage modulus after LF addition. The addition of LF increased stem cell proliferation whereas, SP enhanced the cell migration. Osteogenic gene expression revealed that LF concentration at 25 μg/mg of CSG was optimal for a favourable outcome. To this optimized LF containing CSG, SP was incorporated and 0.05 μg/mg was found to be most effective (CSG-L3S2) in vitro studies. Further, the μ-CT and histological studies confirmed that CSG-L3S2 showed enhanced bone regeneration compared to the controls in critical-sized calvarial defect of mice. Thus the results indicate that a combination of the chemotactic agent (SP), pleiotropic growth protein (LF), and CS in the chitin-PLGA hydrogel could be a promising approach for non-load bearing bone defects., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study reports the application of retention modeling and quality by design practices for reverse-phase liquid chromatographic method development of a new chemical entity. Prior to the retention modeling, preliminary screening experiments were performed for the selection of stationary phase, organic modifiers, and method parameters. Based on the results of preliminary method conditions, t G -T (gradient time - temperature) 2-D modeling with 4 input runs, and t G -T-t c (gradient time-temperature-ternary composition) 3-D modeling with 12 input runs were designed to build a model for achieving the optimized separation. Modeling of reverse phase separations was based on the measurement of both retention times and peak areas. A design space with appropriate input variables and control strategy was established prior to optimization and robustness evaluation following the quality by design framework. DryLab Ⓡ was used to predict the optimized gradient profile and separation temperature. The robustness evaluation was carried out using the multiple factors at a time approach and the control space was established. The interdependence of control space and the control strategy was demonstrated by evaluating method robustness using two levels of system suitability criteria. The predictive accuracy of the retention modeling was established through experimental verification of the in-silico predictions. The quality by design based method development approach demonstrated the in-silico optimization as an integral component of reverse-phase chromatographic method development to evaluate the interplay of factors such as organic modifiers, separation temperature and gradient time, which greatly integrated and enhanced method robustness during method development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Background: The current life expectancy in India is <70 years. Type 2 diabetes mellitus (T2DM) is known to reduce life expectancy by 6-8 years. Hence elderly people with T2DM in India would be rare. We report on the clinical profile of Asian Indian patients with T2DM who lived beyond 90 years of age and compared them with T2DM patients aged 50 to 60 years. Methods: From the diabetes electronic medical records of >470,000 diabetes patients, we identified T2DM patients who had lived ≥90 years and compared them with those in the 50-60 years age group, matched for gender and duration of diabetes. Clinical data included age at last visit, age at diagnosis, duration of diabetes, family history, smoking and alcohol, details of medications, body mass index (BMI), and blood pressure. Biochemical data included fasting and postprandial plasma glucose, glycated hemoglobin, fasting and stimulated C-peptide levels, lipid profile, and renal function studies. Assessment of retinopathy, nephropathy, neuropathy, coronary artery disease (CAD), and peripheral vascular disease (PVD) was also done. Results: A total of 325 T2DM patients aged ≥90 years and 278 T2DM patients aged between 50 and 60 years were selected for the study. Patients aged ≥90 years had higher systolic blood pressure ( P  < 0.001) and lower BMI ( P  < 0.001) than those between 50 and 60 years. Prevalence of retinopathy (29.7% vs. 53.5%) and macroalbuminuria (3.7% vs. 16.0%) was lower in the ≥90 years T2DM patients than in the 50-60 years age group. However, prevalence of neuropathy (89.8% vs. 50.8%), PVD (13.5% vs. 2.0%), and CAD (60.3% vs. 32.0%) was higher among the ≥90 years patients. Eighty-five percent of the T2DM aged ≥90 years were on oral hypoglycemic agents (OHAs), (of whom 64.9% were on sulfonylurea), 12% were on insulin, and 3% on diet alone. Among the 50-60 years old, 87.8% were on OHAs and 12.2% on insulin. Conclusions: This is the first report on the clinical profile of Asian Indians with T2DM aged ≥90 years, and significant differences are seen in their clinical profile compared with younger T2DM patients.

Human mesenchymal stem cells (hMSCs) are prone to senescence and lose their differentiation potential when expanded under nonfavorable conditions. This leads to the underutilization of hMSCs in clinical situations such as bone regeneration. The use of growth factors and small molecules as supplements and changing the physical properties of the cell culture surface have been explored to maintain the self-renewal and differentiation potential of hMSCs during the in vitro expansion phase. Here, we have explored the effect of polyrotaxanes (PRXs) with different molecular mobilities along with either soluble or immobilized fibroblast growth factor 2 (FGF2) in the maintenance of the osteogenic differentiation potential of hMSCs during in vitro expansion. We found that a less expanded shape of the hMSCs was associated with highly mobile PRX surfaces, and less mobile PRX surfaces led to flattened cell morphology. The presence of FGF2 induced further expansion of the cell shape and size. The immobilization of FGF2 helped to improve the yield of hMSCs on highly mobile surfaces by promoting cell attachment to the surfaces. hMSCs cultured on highly mobile PRX surfaces exhibited poor actin cytoskeletal organization and retention of the transcriptional regulator, yes-associated protein (YAP), in cytoplasm in contrast to the hMSCs on less mobile PRX surfaces. When the hMSCs that proliferated under these conditions were collected and subjected to osteogenic differentiation on tissue culture polystyrene (TCPS) surfaces, we found that only the hMSCs cultured on highly mobile PRXs with FGF2 in both soluble and immobilized forms showed mineralization indicative of osteogenic differentiation. Further, we found that hMSCs cultured on highly mobile PRX surfaces expressed higher levels of stemness marker genes, Nanog and Oct4 . These results indicate that culturing hMSCs on PRX surfaces with different molecular mobilities even for a short period of time (4 days) was sufficient to cause a drastic change in the osteogenic potential. From these results, it is suggested that apart from the use of supplements such as FGF2 in its freely soluble or immobilized form, the consideration of proper molecular mobility of the substrates could enable us to design better culture conditions for the hMSCs with osteogenic potential.

The irregular urchin, Metalia persica (Mortensen, 1940), a heart urchin of the family Brissidae, is reported for the first time from the southeastern coast of India. A single specimen was collected from fishing by-catch at Chinna Neelankarai (12º 56' 29.7" N, 80º 15' 36.6" E),  Chennai on April 5, 2018. Metalia persica was previously recorded only from the Persian Gulf (Arabian Gulf). This study records Metalia persica for the first time from Indian waters, in the Bay of Bengal, and elucidates features of the anal fasciole.

Different approaches have been developed to improve the scaffold properties that provide structural support and biological interaction to achieve the desired environment for tissue regeneration. We previously reported that addition of human fibroblast growth factor 18 (hFGF18) to acryloyl group-modified cholesterol-bearing pullulan (CHPOA) nanogel-crosslinked (NanoClik) hydrogels that contain human bone morphogenetic protein 2 (hBMP2) stabilized bone healing in mouse calvarial defect model. In this study, we evaluated the use of disc-shaped dried nanogel-crosslinked gel as carriers of growth factors in order to seek possible clinical application in future. Both conventionally-dried NanoClik disc and nanogel-crosslinked porous (NanoCliP) disc made by freeze-drying that contained the growth factors induced bone healing but not as much as with NanoClik hydrogel application but addition of RGD peptides (RGD-NanoCliP disc) improved the healing. All type of discs showed the same biphasic ovalbumin-Alexa Fluor 488 protein release profile in vitro, an initial burst followed by a gradual sustained release more than one week, which was confirmed in vivo. Histological analysis showed remarkable new bone formation with more calcification in RGD-NanoCliP disc with the growth factors and the osteogenesis appeared to begin in the dura mater in contact with the disc. These observations suggest: (1) the fitness of the durable discs to the bone defect is a critical factor for bone healing, which is supplemented by addition of RGD peptides, (2) the porosity is suitable for osteoblast recruitment, (3) growth factor release pattern of the CHPOA nanogel based gels is ideal for bone healing.

Bone is a metabolically active organ that undergoes continuous remodeling throughout life. However, many complex skeletal defects such as large traumatic bone defects or extensive bone loss after tumor resection may cause failure of bone healing. Effective therapies for these conditions typically employ combinations of cells, scaffolds, and bioactive factors. In this review, we pay attention to one of the three factors required for regeneration of bone, bioactive factors, especially the fibroblast growth factor (FGF) family. This family is composed of 22 members and associated with various biological functions including skeletal formation. Based on the phenotypes of genetically modified mice and spatio-temporal expression levels during bone fracture healing, FGF2, FGF9, and FGF18 are regarded as possible candidates useful for bone regeneration. The role of these candidate FGFs in bone regeneration is also discussed in this review.

Introduction: The use of complementary and alternative medicine (CAM) as a source of cure has gained much spectrum worldwide, despite skeptics and advocates of evidence-based practice conceptualized such therapies as human nostrum., Objective: This study aimed to explore the factors affecting CAM use among rural communities in Malaysia., Methods: A cross-sectional study was carried out on 288 occupants across four rural villages within the District of Selama, Perak, Malaysia. A survey that consisted of socio-economic characteristics, history of CAM use and the validated Holistic Complementary and Alternative Medicine Questionnaire (HCAMQ) were used., Results: The prevalence of self-reported CAM use over the past one year was 53.1%. Multiple logistic regression analyses yielded three significant predictors of CAM use: monthly household income of less than MYR 2500, higher education level, and positive attitude towards CAM., Conclusion: Psycho-socioeconomic factors were significantly associated with CAM use among rural communities in Malaysia.