Development of Anisotropic Electrically Conductive GNP-Reinforced PCL-Collagen Scaffold for Enhanced Neurogenic Differentiation under Electrical Stimulation.

The internal electric field of the human body plays a crucial role in regulating various biological processes, such as, cellular interactions, embryonic development and the healing process. Electrical stimulation (ES) modulates cytoskeleton and calcium ion activities to restore nervous system functioning. When exposed to electrical fields, stem cells respond similarly to neurons, muscle cells, blood vessel linings, and connective tissue (fibroblasts), depending on their environment. This study develops cost-effective electroconductive scaffolds for regenerative therapy. This was achieved by incorporating carboxy functionalized graphene nanoplatelets (GNPs) into a Polycaprolactone (PCL)-collagen matrix. ES was used to assess the scaffolds' propensity to boost neuronal differentiation from MSCs. This study reported that aligned GNP-reinforced PCL-Collagen scaffolds demonstrate substantial MSC differentiation with ES. This work effectively develops scaffolds using a simple, cost-effective synthesis approach. The direct coupling approach generated a homogeneous electric field to stimulate cells cultured on GNP-reinforced scaffolds. The scaffolds exhibited improved mechanical and electrical characteristics, as a result of the reinforcement with carbon nanofillers. In vitro results suggest that electrical stimulation helps differentiation of mesenchymal stem-like cells (MSC-like) towards neuronal. This finding holds great potential for the development of effective treatments for tissue injuries related to the nervous system.

Assessment of the mechanistic role of an Indian traditionally used ayurvedic herb Bacopa monnieri (L.)Wettst. for ameliorating oxidative stress in neuronal cells.

ETHNOPHARMACOLOGICAL RELEVANCE: This study has important ethnopharmacological implications since it systematically investigated the therapeutic potential of Bacopa monnieri(L.) Wettst. (Brahmi) in treating neurological disorders characterized by oxidative stress-a growing issue in the aging population. Bacopa monnieri, which is strongly rooted in Ayurveda, has long been recognized for its neuroprotective and cognitive advantages. The study goes beyond conventional wisdom by delving into the molecular complexities of Bacopa monnieri, particularly its active ingredient, Bacoside-A, in countering oxidative stress. The study adds to the ethnopharmacological foundation for using this herbal remedy in the context of neurodegenerative disorders by unravelling the scientific underpinnings of Bacopa monnieri's effectiveness, particularly at the molecular level, against brain damage and related conditions influenced by oxidative stress. This dual approach, which bridges traditional wisdom and modern investigation, highlights Bacopa monnieri's potential as a helpful natural remedy for oxidative stress-related neurological diseases. AIM OF THE STUDY: The aim of this study is to investigate the detailed molecular mechanism of action (in vitro, in silico and in vivo) of Bacopa monnieri (L.) Wettst. methanolic extract and its active compound, Bacoside-A, against oxidative stress in neurodegenerative disorders. MATERIALS AND METHODS: ROS generation activity, mitochondrial membrane potential, calcium deposition and apoptosis were studied through DCFDA, Rhodamine-123, FURA-2 AM and AO/EtBr staining respectively. In silico study to check the effect of Bacoside-A on the Nrf-2 and Keap1 axis was performed through molecular docking study and validated experimentally through immunofluorescence co-localization study. In vivo antioxidant activity of Bacopa monnieri extract was assessed by screening the oxidative stress markers and stress-inducing hormone levels as well as through histopathological analysis of tissues. RESULTS: The key outcome of this study is that the methanolic extract of Bacopa monnieri (BME) and its active component, Bacoside-A, protect against oxidative stress in neurodegenerative diseases. At 100 and 20 µg/ml, BME and Bacoside-A respectively quenched ROS, preserved mitochondrial membrane potential, decreased calcium deposition, and inhibited HT-22 mouse hippocampus cell death. BME and Bacoside-A regulated the Keap1 and Nrf-2 axis and their downstream antioxidant enzyme-specific genes to modify cellular antioxidant machinery. In vivo experiments utilizing rats subjected to restrained stress indicated that pre-treatment with BME (50 mg/kg) downregulated oxidative stress markers and stress-inducing hormones, and histological staining demonstrated that BME protected the neuronal cells of the Cornu Ammonis (CA1) area in the hippocampus. CONCLUSIONS: Overall, the study suggests that Bacopa monnieri(L.) Wettst. has significant potential as a natural remedy for neurodegenerative disorders, and its active compounds could be developed as new drugs for the prevention and treatment of oxidative stress-related diseases.

Electro-conductive chitosan/graphene bio-nanocomposite scaffold for tissue engineering of the central nervous system.

Degenerative central nervous system (CNS) disorders and traumatic brain injuries are common nowadays. These may induce the loss of neuronal cells and delicate connections essential for optimal CNS function. The CNS tissue has restricted regeneration ability, hindering the development of effective therapies. Developing cell and tissue instructive materials may bring up new treatment possibilities. In this study, chitosan-graphene nano platelets (GNPs) composite films were developed to regenerate brain cells. This study evaluates the effects of GNP concentration (0.5, 1 and 2 wt%) and their alignment on mechanical, electrical, surface, protein adsorption and biological properties of the regenerative scaffolds. Incorporating and aligning GNPs into chitosan matrix improved all the physical and biological properties. On reinforced scaffolds, HT22 cell morphology mimics pyramidal brain cells, which are responsible for the brain's highly branched neural network. Additionally, the reinforced scaffolds supported Mesenchymal Stem like Cells growth and were biocompatible in vivo. The alignment of GNPs in the chitosan matrix offered the appropriate physicochemical and biological properties to promote adhesion, proliferation and shape morphogenesis of hippocampal HT22 neuronal cells. Overall, this study delineates the enormous potential offered by the GNP-reinforced scaffolds for regeneration of central nervous system, especially the brain.

4D Printed Programmable Shape-Morphing Hydrogels as Intraoperative Self-Folding Nerve Conduits for Sutureless Neurorrhaphy.

There are only a few reports of implantable 4D printed biomaterials, most of which exhibit slow deformations rendering them unsuitable for in situ surgical deployment. In this study, a hydrogel system is engineered with defined swelling behaviors, which demonstrated excellent printability in extrusion-based 3D printing and programmed shape deformations post-printing. Shape deformations of the spatially patterned hydrogels with defined infill angles are computationally predicted for a variety of 3D printed structures, which are subsequently validated experimentally. The gels are coated with gelatin-rich nanofibers to augment cell growth. 3D-printed hydrogel sheets with pre-programmed infill patterns rapidly self-rolled into tubes in vivo to serve as nerve-guiding conduits for repairing sciatic nerve defects in a rat model. These 4D-printed hydrogels minimized the complexity of surgeries by tightly clamping the resected ends of the nerves to assist in the healing of peripheral nerve damage, as revealed by histological evaluation and functional assessments for up to 45 days. This work demonstrates that 3D-printed hydrogels can be designed for programmed shape changes by swelling in vivo to yield 4D-printed tissue constructs for the repair of peripheral nerve damage with the potential to be extended in other areas of regenerative medicine.

Biotribological behaviour, biodegradability and osteocompatibility of Mg-3Zn/HA composite based intramedullary inserts in avian model.

Bioactivity, structural integrity and tribological behaviour of biodegradable orthopaedic fracture fixing accessories considerably impact their actual performance in the body environment. Immune system in the living body quickly responds to the wear debris as foreign material and begins a complex inflammatory response. Magnesium (Mg) based biodegradable implants are widely studied for temporary orthopaedic applications, due to their similar elastic modulus and density to natural bones. However, Mg is highly vulnerable to corrosion and tribological damage in actual service conditions. To address these challenges via a combined approach, the Mg-3 wt% Zinc (Zn)/x hydroxyapatite (HA, x = 0, 5 and 15 wt%) based composites (fabricated via spark plasma sintering route) are evaluated in terms of biotribocorrosion and in-vivo biodegradation and osteocompatibility behaviour in an avian model. The addition of 15 wt% HA in the Mg-3Zn matrix has significantly enhanced the wear and corrosion resistance in the physiological environment. X-ray radiograph analysis of the Mg-HA-based intramedullary inserts implanted in the humerus bone of birds showed consistent progression of degradation and positive tissue response up to 18 weeks. The 15 wt% HA reinforced composites have shown better bone regeneration properties than other inserts. This study provides new insights into developing next-generation Mg-HA-based biodegradable composites for temporary orthopaedic implants, with excellent biotribocorrosion behaviour.

Pterostilbene-isothiocyanate impedes RANK/TRAF6 interaction to inhibit osteoclastogenesis, promoting osteogenesis in vitro and alleviating glucocorticoid induced osteoporosis in rats.

Prolonged glucocorticoid treatment often leads to glucocorticoid-induced osteoporosis (GIOP), a common iatrogenic complication. This study has explored the anti-osteoporotic potential of semi-synthetic compound, pterostilbene isothiocyanate (PTER-ITC) in GIOP rat model and bone formation potential in vitro. Dysregulated bone-remodelling leads to osteoporosis. PTER-ITC has shown anti-osteoclastogenic activity in vitro. However, its molecular target remains unidentified, which has been explored in this study through in silico and experimental approaches. Alizarin Red S and von-Kossa staining, and alkaline phosphatase (ALP) activity showed the osteogenic differentiation potential of PTER-ITC in pre-osteoblastic mouse MC3T3-E1 and human hFOB 1.19 cells, further, confirmed through the expressions of osteogenic markers at transcriptional (RT-qPCR) and translational (immunoblotting) levels. The anti-osteoclastogenic property of PTER-ITC was confirmed through inhibition of actin ring formation in mouse RAW 264.7 and human THP-1 macrophagic cells. Molecular docking and molecular dynamic simulation showed that PTER-ITC inhibited the crucial osteoclastogenic RANK/TRAF6 interaction, which was further confirmed biochemically through co-immunoprecipitation assay. Osteoporotic bone architecture [validated through scanning electron microscopy (SEM), X-ray radiography, and micro-computed tomography (µ-CT)], physiology (confirmed through compression testing, Young's modulus and stress versus strain output) and histology (verified through hematoxylin-eosin, Alizarin Red S, von-Kossa and Masson-trichrome staining) of PTER-ITC-treated GIOP female Wistar rats were assuaged. Osteoporotic amelioration through PTER-ITC treatment was further substantiated through serum biomarkers, like, parathyroid hormone (PTH), ALP, calcium (Ca2+), Procollagen type I N-terminal propeptide (P1NP), and 25-hydroxy vitamin D. In conclusion, this study identifies the molecular target of PTER-ITC in impeding osteoclastogenesis and facilitating osteogenesis to ameliorate osteoporosis.

Copper and cobalt doped bioactive glass-fish dermal collagen electrospun mat triggers key events of diabetic wound healing in full-thickness skin defect model.

The wounds arising out of underlying hyperglycemic conditions such as diabetic foot ulcers demand a multifunctional tissue regeneration approach owing to several deficiencies in the healing mechanisms. Herein, four different types of electrospun microfibers by combining Rohu fish skin-derived collagen (Fcol) with a bioactive glass (BAG)/ion-doped bioactive glass, namely, Fcol/BAG, Fcol/CuBAG, Fcol/CoBAG, and Fcol/CuCoBAG was developed to accelerate wound healing through stimulation of key events such as angiogenesis and ECM re-construction under diabetic conditions. SEM analysis shows the porous and microfibrous architecture, while the EDX mapping provides evidence of the incorporation of dopants inside various inorganic-organic composite mats. The viscoelastic properties of the microfibrous mats as measured by a nano-DMA test show a higher damping factor non-uniform tan-delta value. The maximum ultimate tensile strength and toughness are recorded for fish collagen with copper doped bioactive glass microfibers while the least values are demonstrated by microfibers with cobalt dopant. In vitro results demonstrate excellent cell-cell and cell-material interactions when human dermal fibroblasts (HDFs) were cultured over the microfibers for 48 h. When these mats were applied over full-thickness diabetic wounds in the rabbit model, early wound healing is attained with Fcol/CuBAG, Fcol/CoBAG, and Fcol/CuCoBAG microfibers. Notably, these microfibers-treated wounds demonstrate a significantly (p < 0.01) higher density of blood vessels by CD-31 immunostaining than control, Duoderm, and Fcol/BAG treated wounds. Mature collagen deposition and excellent ECM remodeling are also evident in wounds treated with fish collagen/ion-doped bioactive glass microfibers suggesting their positive role in diabetic wound healing.

Single unit functionally graded bioresorbable electrospun scaffold for scar-free full-thickness skin wound healing.

Full-thickness wounds are difficult to heal spontaneously. Scaffolds, meant for treating full-thickness wounds, should ensure proper tissue regeneration, both structurally and functionally. An ideal scaffold should mimic the physical, mechanical and biochemical properties of natural skin. However, available mono- or bi-layer skin scaffolds lack in the precise architecture and functionality, thus, failing to provide scar-free regeneration of full-thickness skin wounds. These unmet challenges of scar-free skin regeneration have been addressed in the present study for the first time. This research deals with the synthesis of a low-cost, structurally and functionally graded single unit biodegradable polymeric scaffold. The functional gradient in this scaffold was achieved by varying polymer concentration and electrospinning parameters. This gradient in the scaffold provided the required microenvironment for proper functional and structural reconstruction of all the layers of natural skin. The mechanical property of the scaffold matched that of the natural skin. Besides, the degradation kinetics of the scaffold was in coordination with the regeneration time for the full-thickness wound. The porosity and hydrophilicity gradients of the scaffold helped it mimic the in vivo hypodermal, dermal and epidermal microenvironments of the skin, simultaneously. Co-culturing PCS-201 (dermal fibroblasts) and HaCaT (keratinocytes) on the scaffold resulted in successful regeneration through cellular proliferation, differentiation and organization of the skin tissue. The scaffold also displayed better wound healing in vivo, in terms of speedy wound closure and proper tissue regeneration, in comparison to the standard treatment. Altogether, this study successfully established a simple, one-step synthesis process of a functionally graded, bioresorbable scaffold for scar-free, native-like, structural and functional regeneration of full-thickness skin wounds. Due to cost-effectiveness, easy synthesis process and microarchitectural features, the designed scaffold possesses a potential of translation to a good commercial wound healing product.

Enhanced neurogenic differentiation on anisotropically conductive carbon nanotube reinforced polycaprolactone-collagen scaffold by applying direct coupling electrical stimulation.

Electrical stimulation is conducive to neural regeneration. Different types of stimuli propagation patterns are required for regenerating cells in peripheral and central nervous systems. Modulation of the pattern of stimuli propagation cannot be achieved through external means. Reinforcing scaffolds, with suitably shaped conductive second phase materials, is a promising option in this regard. The present study has taken the effort of modulating the pattern (arrangement) of reinforced phase, namely multiwalled carbon nanotubes (MWCNT), in a biodegradable scaffold made of PCL-collagen mixture, by applying an external electric field during curing. Because of their extraordinary physical properties, MWCNTs have been selected as nano-reinforcement for this study. The nature of reinforcement affects the electrical conductivity of the scaffold and also determines the type of cell it can support for regeneration. Further, electrical stimulation, applied during incubation, was observed to have a positive influence on differentiating neural cells in vitro. However, the structure of the nano-reinforcement determined the differentiated morphology of the cells. Reinforced MWCNTs being tubes, imparted bipolarity to the cells. Therefore, these scaffolds, coupled with electrical stimulation possess significant potential to be used for directional regeneration of the nerves.

Brassica oleracea Extracts Prevent Hyperglycemia in Type 2 Diabetes Mellitus.

This study investigated the protective effect of extracts from flowers of Brassica oleracea L. var. italica Plenck on type 2 diabetes mellitus and its associated disorders. Three different doses of each extract (petroleum ether, ethanol, and aqueous) were administered orally for 42 days. Biochemical parameters, behavioral studies, and histological studies were measured at different periods. Mortality was found to be nil up to 2,000 mg/kg. Statistically significant (P<0.001) improvement in serum glucose level was observed in the groups receiving 400 mg/kg of petroleum ether, aqueous, or ethanol extracts compared with the negative control group. Insulin level was decreased by aqueous extracts, whereas lipid profiles were improved by aqueous and ethanol extracts. A reduction in transfer latency was observed in treatments of all three extract types. Ethanol extract treatment (400 mg/kg) showed maximum percentage inhibition in a lipid peroxidation assay. Additionally, the aqueous and ethanol extract treatments markedly reduced tumor necrosis factor-α, interleukin-6, and glycosylated hemoglobin levels. Histological results showed that high doses of extracts alleviated the damages induced by type 2 diabetes mellitus in various organs and bones. Based on the results of this study, it can be concluded that B. oleracea has the potential to alleviate type 2 diabetes mellitus.

Assessment of protein adhesion behaviour and biocompatibility of magnesium/Co-substituted HA-based composites for orthopaedic application.

Protein adsorption has a great influence on Mg-based metallic implants, which affects cell attachment and cell growth. Adsorption of the proteins (via electrostatic interaction, hydrophobic/hydrophilic, and hydrogen-bonding) on the implant surface is greatly influenced by the surface chemistry of the implant. Hydroxyapatite (HA) is a class of CaP ceramic, beneficial for protein adsorption as it possesses Ca2+ and PO43- in it, which are believed to be the protein binding sites on the HA surface. Moreover, HA is the popular choice for reinforcement in the magnesium matrix owing to its similarity with bone mineral composition. However, negligible interaction between HA and Mg particles during sintering is the major limitation for frequent usage of Mg-HA implants. Doping of HA with Mg2+ and Zn2+ (CoHA) ions leads to its chemistry similar to natural apatite in human bone and facilitates comparatively better bonding with the MgZn matrix. This study mainly aims to delve into the protein adsorption behaviour of Magnesium/Co-substituted HA-based Composites (M3Z-CoHA) along with their biocompatibility. Qualitative and quantitative protein adsorption analysis shows that the addition of 15 wt% CoHA to Mg matrix enhanced protein adsorption by ~60% and renders cell viability >90% after day 1, supporting cellular growth and proliferation. The implants also initiated osteogenic differentiation of the cells after day 7. The leached-out products from all the composites showed no toxicity. The morphology of the cells in all the composites was found as healthy as the control cells. Overall, the composite with 15 wt% HA reinforcement (M3Z-15CoHA) has shown favourable protein adsorption behaviour and cytocompatibility.

Promises of Functionally Graded Material in Bone Regeneration: Current Trends, Properties, and Challenges.

Functionally graded materials (FGMs) are emerging materials systems, with structures and compositions gradually changing in a particular direction. Consequently, the properties of the materials gradually change in the desired direction to achieve particular nonhomogeneous service demands without abrupting the compositional and behavioral interface at the macroscale. FGMs have been found to have high potential as orthopedic implants; because the functional gradient can be adapted in such a manner that the core of FGM should be compatible with the density and strength of bone, interlayers can maintain the structural integrity and outermost layers would provide bioactivity and corrosion resistance, thus overall tailoring the stress shielding effect. This review article discusses the typical FGM systems existing in nature and the human body, focusing on bone tissue. Further, the reason behind the application of these FGMs systems in orthopedic implants is explored in detail, considering the physical and biological necessities. The substantial focus of the present critical review is devoted to two primary topics related to the usage of FGMs for orthopedic implants: (1) the synthesizing techniques currently available to produce FGMs for load-bearing orthopedic applications and (2) the properties, such as mechanical, structural, and biological behavior of the FGMs. This review article gives an insight into the potential of FGMs for orthopedic applications.

Nutraceutical regulation of miRNAs involved in neurodegenerative diseases and brain cancers.

The human brain is a well-connected, intricate network of neurons and supporting glial cells. Neurodegenerative diseases arise as a consequence of extensive loss of neuronal cells leading to disruption of their natural structure and function. On the contrary, rapid proliferation and growth of glial as well as neuronal cells account for the occurrence of malignancy in brain. In both cases, the molecular microenvironment holds pivotal importance in the progression of the disease. MicroRNAs (miRNA) are one of the major components of the molecular microenvironment. miRNAs are small, noncoding RNAs that control gene expression post-transcriptionally. As compared to other tissues, the brain expresses a substantially high number of miRNAs. In the early stage of neurodegeneration, miRNA expression upregulates, while in oncogenesis, miRNA expression is gradually lost. Neurodegeneration and brain cancer is presumed to be under the influence of identical pathways of cell proliferation, differentiation and cell death which are tightly regulated by miRNAs. It has been confirmed experimentally that miRNA expression can be regulated by nutraceuticals - macronutrients, micronutrients or natural products derived from food; thereby making dietary supplements immensely significant for targeting miRNAs having altered expression patterns during neurodegeneration or oncogenesis. In this review, we will discuss in detail, about the common miRNAs involved in brain cancers and neurodegenerative diseases along with the comprehensive list of miRNAs involved separately in both pathological conditions. We will also discuss the role of nutraceuticals in the regulation of those miRNAs which are involved in both of these pathological conditions.

Decellularized xenogenic cartilage extracellular matrix (ECM) scaffolds for the reconstruction of osteochondral defects in rabbits.

The use of decellularized native allogenic or xenogenic cartilaginous extracellular matrix (ECM) biomaterials is widely expanding in the fields of tissue engineering and regenerative medicine. In this study, we aimed to develop an acellular, affordable, biodegradable, easily available goat conchal cartilaginous ECM derived scaffolding biomaterial for repair and regeneration of osteochondral defects in rabbits. Cartilages harvested from freshly collected goat ears were decellularized using chemical agents, namely, hypotonic-hypertonic (HH) buffer and Triton X-100 solution, separately. The morphologies and ultrastructure orientations of the decellularized cartilages remained unaltered in spite of complete cellular loss. Furthermore, when the acellular cartilaginous ECMs were cultured with murine mesenchymal stem cells (MSCs) (C3H10T1/2 cells), cellular infiltration and proliferation were thoroughly monitored using SEM, DAPI and FDA stained images, whereas the MTT assay proved the biocompatibility of the matrices. The increasing amounts of secreted ECM proteins (collagen and sGAG) indicated successful chondrogenic differentiation of the MSCs in the presence of the treated cartilage samples. In vivo biocompatibility studies showed no significant immune response or tissue rejection in the treated samples but tissue necrosis in control samples after 3 months. Upon implantation of the constructs in rabbits' osteochondral defects for 3 months, the histological and micro-CT evaluation revealed significant enhancement and regeneration of neocartilage and subchondral bony tissues. The IGF-1 loaded cartilaginous constructs showed comparatively better healing response after 3 months. Our results showed that decellularized xenogenic cartilaginous biomaterials preserved the bioactivity and integrity of the matrices that also favored in vitro stem cell proliferation and chondrogenic differentiation and enabled osteochondral regeneration, thus paving a new way for articular cartilage reconstruction.

Synthesis and evaluation of magnesium/co-precipitated hydroxyapatite based composite for biomedical application.

Owing to its inductive attributes, hydroxyapatite is an ideal reinforcement to tailor the degradation kinetics of magnesium-based temporary orthopedic implants. However, the large difference in the melting temperature of hydroxyapatite and magnesium lead to an insignificant interaction between them during the sintering process, which has been a major limitation in their consolidation. Doping of pure HA with Mg2+ and Zn2+ ions could be a viable solution by making it coherent with the Mg matrix. Further, such doping also results in a chemistry more similar to the natural apatite in human bone. In this study, Mg2+ and Zn2+ ions doped hydroxyapatite (CoHA) is synthesized and reinforced to obtain high density in Mg-based composites, fabricated through spark plasma sintering. Composite with 15 wt % CoHA offered ~113% improvement in the ultimate compressive strength. Higher relative density, due to improved consolidation, might be the reason for higher mechanical strength. Hydrogen evolution (up to 64 h) and static immersion studies (up to 28 days) revealed comparatively higher corrosion resistance for 10 wt% CoHA composites. This study gives insight into the potential of fabrication and designing of the M3Z-CoHA composites for temporary orthopedic implants.

Development and Characterization of Acellular Caprine Choncal Cartilage Matrix for Tissue Engineering Applications.

Because of poor regenerative capabilities of cartilage, reconstruction of similar rigidity and flexibility is difficult, challenging, and restricted. The aim of the present investigation was to develop cost-effective acellular xenogeneic biomaterial as cartilage substitution. Two novel biometrics have been developed using different chemical processes (Na-deoxycholate + SDS and GndHCl + NaOH) to decellularize caprine (goat) ear cartilage and further extensively characterized before preclinical investigation. Complete cell removal was ascertained by hematoxylin and eosin staining followed by DNA estimation. No adverse effect on extracellular matrix (ECM) was found by quantifying collagen and sulfated glycosaminoglycans (sGAG) content as well as collagen, sGAG and elastin staining. Results showed no drastic changes in ECM structure apart from desired sGAG loss. Scanning electron microscopy images confirmed cellular loss and unaltered orientation. Nano-indentation study on cartilage matrices indicated interesting output showing better results among decellularized groups. Increased elastic modulus and hardness indicated better stiffness and more active energy dissipation mechanism due to decellularization. Fluid uptake and retention property remained unchanged after decellularization as analyzed by swelling behavior study. Additionally, acellular materials were confirmed to be nonreactive and nonhemolytic as assessed by in vitro hemocompatibility study. In vivo study (up to 3 months) on rabbits showed no symptoms of graft rejection/ tissue necrosis, established through postoperative histology and biochemical analyses of tissue explants. With regard to size, shape, biomechanics, source of origin and nonimmunogenic properties, these developed materials can play versatile role in biomedical/ clinical applications and pave a new insight as alternatives in cartilage reconstruction.

Biocompatibility and biodegradability evaluation of magnesium-based intramedullary bone implants in avian model.

At present days osteosynthesis modalities for avian fracture management are inadequate. External coaptation is the most practiced method however, specialized clinics have started introducing intramedullary pinning, external skeletal fixation with tie-in-fixation for fracture immobilization. Magnesium (Mg) based biomaterials are trustable developments in the field of orthopedics compared to their permanent stainless steel counterparts concerning long term adverse reaction. Mg implants are becoming promising for their use as intramedullary accessories because they are bioresorbable with high strength-weight ratio and the similarities in density and elastic modulus to the natural bones. However, their severe biodegradation trait restricts frequent use as load-bearing orthopedic implants. In this study, the biocompatibility and biodegradability of Mg based intramedullary cylindrical spacers (2.4 mm diameter × 8 mm height) reinforced with 0, 5, 15 wt% of hydroxyapatite (HA, Ca10 (PO4 )6 (OH)2 ) were evaluated in 18 Uttara-fowl birds. Clinical, radiological (from immediate postoperative days till 24th week), biochemical (first three postoperative weeks) and histopathological study of test bone were carried out to evaluate implant degradation and osteocompatibility. Biodegradation of Mg-3Zn/0HA and Mg-3Zn/15HA initiated a bit earlier at second week of implantation, while that of Mg-3Zn/5HA at 3-fourth week, and found biocompatible and biodegradable with no observable clinical and histopathological changes.

Functionally gradient magnesium-based composite for temporary orthopaedic implant with improved corrosion resistance and osteogenic properties.

Magnesium (Mg) is a potential alternative for conventional orthopaedic implant materials owing to its biodegradation behavior and physical characteristics similar to natural human bone. Due to its biomimetic mechanical attributes, Mg in orthopaedic applications could reduce the risk of the 'stress shielding effect'. However, the major limitation of Mg is its high in-vivo corrosion rate. Thermal sprayed coatings of osteoconductive ceramics like hydroxyapatite (HA) have been explored as a potential solution, albeit with limited success due to the low melting point of Mg, which restricts the ease of fabricating surface-adherent ceramic coating. The present study focuses on overcoming this limitation through a Mg-HA functionally gradient material (FGM) system, which is expected to provide a highly corrosion-resistant surface and uniform mechanical integrity throughout the structure. In addition to corrosion resistance, the FGM system has improved biocompatibility and osteoconductivity without compromising its mechanical stability. The FGM, with a compositional gradient of Mg-HA composite, consisting of Mg at the core and increasing HA towards the outer layer, has been fabricated through spark plasma sintering. Mechanical properties of the overall structure were better than those of the best individual composite. More importantly, corrosion resistance of the FGM structure was significantly improved (~154%) as compared to individual composites. In addition, alkaline phosphatase activity, osteogenic gene expression and cell viability, all pertaining to efficient osteogenic differentiation, were enhanced for FGM and 15 wt% HA reinforced composites. These observations suggest that the FGM structure is promising for temporary biodegradable orthopaedic implants.

Assessment of biomechanical stability and formulation of a statistical model on magnesium based composite in two different milieus.

Magnesium (Mg) based temporary implants are an appealing new solution to counter the problems associated with the currently available temporary orthopaedic implants, used in fracture fixing. To make the extensive use of Mg-based implants in-vivo, mechanical integrity in the physiological environment is a prerequisite. This study presents an insight into the biomechanical stability of Mg-3Zn/HA (0, 5, and 15 wt % of HA) composites in two different milieus (simulated body fluid (SBF) and serum contained SBF (m-SBF)). After 14 days of static immersion in SBF, ~65% mechanical strength was compromised in the case of 15 wt % HA reinforcement. However, the degradation rate was slowed down by ~35% with the addition of 15 wt % HA in Mg-3Zn. Mg-3Zn/HA composite, when soaked in both fluids, was found to induce apatite layer formation on the surfaces for several days. However, in the case of m-SBF immersion, 15 wt % HA facilitated less precipitation of apatite growth when compared to SBF immersion. Nevertheless, m-SBF immersed 15 wt % HA composite facilitated better corrosion resistance and excellent mechanical stability after 14 days of immersion. The approach thereby assists in establishing an effective mechanism between the degradation and mechanical stability in in-vitro immersion. In addition, this study has also developed a semi-empirical model for prediction of the compressive strength of these composites as a function of the number of days of immersion and the content of hydroxyapatite (HA). This semi-empirical model will help in predicting the biomechanical stability for long-term in-vitro exposures, which might be of use in evaluating the effect of the in-vivo environment.

Anisotropically Conductive Biodegradable Scaffold with Coaxially Aligned Carbon Nanotubes for Directional Regeneration of Peripheral Nerves.

Fascicular rearrangement of an injured peripheral nerve requires reconnection of nerve sprouts from anterior and Büngner bands from distal sides of the lesion, failing to which leads to inefficient regeneration of the injured nerve. However, existing neural scaffolds have limited neuroregeneration efficiency because of either the lack of alignment of fibers and a conductive second phase, leading to compromised electrical conductivity, or the lack of extracellular matrix components and in vivo validation. The present study reports a biocompatible, multiwall carbon nanotube (MWCNT)-reinforced, anisotropically conductive, electrospun, aligned nanofibrous scaffold, ensuring maximal peripheral nerve regeneration. Electrospinning parameters were modulated to deposit random and parallel fibers in separate scaffolds for comparative analysis on the effect of fiber alignment on regeneration. Both types of scaffolds were reinforced with MWCNTs to impart electrical conductivity. Nonreinforced scaffolds were nonconductive. In this comparative study, MWCNT-reinforced, aligned scaffolds showed better tensile property with increased conductivity along the direction of alignment, thereby ensuring an escalated neural-regeneration rate. Collectively, in vitro studies established the scaffolds to be highly biocompatible, promoting cell growth and proliferation. With 85% more anisotropic conductivity in the direction of the alignment and the degradation kinetics tuned to the regeneration regime, the MWCNT-reinforced, aligned scaffold efficiently healed injured sciatic nerves in rats within 30 days. Rigorous revivification of the tissue was due to coordinated Wallerian degeneration and expedited guided axonal regeneration. Structural and functional analysis of nerves in vivo showed the aligned, MWCNT-reinforced scaffold to be very efficient in peripheral sciatic nerve regeneration. This study notes the efficacy of the coaxially aligned, MWCNT-reinforced neural scaffold, with a capability of establishing remarkable advancement in the field of peripheral neural regeneration.