Nickel-ion substituted hydroxyapatite matrices for metal-affinity chromatographic purification of recombinant proteins.

Hydroxyapatite (HAp) is a calcium phosphate ceramic, widely used as a matrix for protein chromatography. The crystal structure of HAp is amenable to a wide range of substitutions, thus allowing for the alteration of its properties. In this study, nickel-ion substituted HAp (NiSHAp) was synthesized using a wet-precipitation method, followed by spray drying. This resulted in the structural incorporation of nickel ions within well-defined microspheres, which were suitable for chromatographic applications. The chromatographic experiments were conducted with NiSHAp and compared with spray-dried hydroxyapatite (SHAp) matrices. Protein purification experiments were conducted using refolded recombinant L-asparaginase (L-Asp), which was produced as inclusion bodies in Escherichia coli. The results showed that NiSHAp effectively adsorbed L-Asp, which was selectively eluted using a phosphate buffer, surpassing the efficiency of imidazole-based elution. In contrast, SHAp showed weaker binding and lower selectivity. The significance of this study lies in developing a scalable NiSHAp matrix for protein purification, especially for large-scale applications. The NiSHAp matrix offers a cost-effective alternative to commercial immobilized metal affinity chromatography (IMAC) adsorbents, especially for purifying His-tagged proteins. This innovative approach exhibits the advantages of mixed-mode chromatography by combining the properties of hydroxyapatite and IMAC in a single matrix, with the potential of improved industrial-scale protein purification.

Combinational delivery of anticancer drugs for osteosarcoma treatment using electrosprayed core shell nanocarriers.

In bone cancer treatment, local delivery of chemotherapeutic agents is preferred compared to other routes of administration. Delivery of multiple drugs using biodegradable carriers improves the treatment efficiency and overcomes drug resistance and toxicity. With this approach, we have developed multilayer biodegradable core shell nanoparticles (NPs) using the electro-spraying technique to deliver methotrexate (MTX) and doxorubicin (DOX) for the treatment of osteosarcoma. These core-shell NPs with a mean particle size of 212 ± 41 nm consist of hydroxyapatite (HA) and DOX as core with the outer shell made of chitosan (CH) followed by polycaprolactone (PCL) with MTX. The encapsulation efficiency of MTX was around 85% and DOX was 38%. In vitro drug release studies were performed in phosphate buffered saline (PBS) at pH 5 and pH 7.4 for 8 days. Different release profiles were observed in both acidic and alkaline pH. The sequential release of MTX followed by DOX was observed in both pH in sustained manner. Human osteosarcoma MG 63 (OMG-63) cells lines were used to test the cytotoxicity of drug loaded NPs. Multi-drug encapsulated bioresorbable and biodegradable electro-sprayed core shell NPs will be promising as a bone substitute for the treatment of osteosarcoma.

Lower oesophageal peptic stricture after laparoscopic sleeve gastrectomy: World's first case report.

Laparoscopic sleeve gastrectomy (LSG) is the most commonly performed bariatric surgery worldwide. De novo gastroesophageal reflux disease after LSG has been reported in the range of 0%-34.9%. Benign lower oesophageal peptic stricture is rare and has not been reported till date. We present the first case report of benign oesophageal peptic stricture post-sleeve gastrectomy and its management. The management modalities for peptic stricture post-LSG include proton pump inhibitors, endoscopic dilatation and surgical management. Revisional Roux-en-Y gastric bypass along with optimal usage of serial dilatation and medical treatment has been shown to be an effective treatment for the same.

Eggshell derived brushite bone cement with minimal inflammatory response and higher osteoconductive potential.

Brushite cements are known for excellent osteoconductive and degradation properties, however, its widespread use is limited due to rapid setting time and poor mechanical properties. The eggshell derived calcium phosphates exhibits improved physical and biological properties due to the presence of biologically relevant ions. In this study, eggshell derived brushite cement (EB) was fabricated using ß-tricalcium phosphate synthesized from eggshells. The presence of trace elements in EB prolonged its setting time. The size of brushite crystals in EB was found to be smaller than the pure brushite cement (PB) leading to increased initial compressive strength and higher in vitro degradation rate. The L6 and MG63 cell lines exhibited good biocompatibility with the cement at the end 72 h. In vivo studies of the cements were performed in rat calvarial defect model. Micro CT analysis showed faster degradation and accelerated bone formation in EB filled defect. Histological studies revealed infiltration of inflammatory cells into the implant site for both the cements till 6th week. However, inflammation was found to be significantly reduced at the 12th week in EB compared to PB leading to complete bone bridge formation. Multi-ion substituted EB seems to be a potential bone substitute material with a reasonable setting time for ease of handling, higher mechanical strength, minimal inflammatory response and higher bone regeneration.

Ceramic core with polymer corona hybrid nanocarrier for the treatment of osteosarcoma with co-delivery of protein and anti-cancer drug.

For the treatment of metastatic bone cancer, local delivery of therapeutic agents is preferred compared to systemic administration. Delivery of an anti-cancer drug and a protein that helps in bone regeneration simultaneously is a challenging approach. In this study, a nanoparticulate carrier which delivers a protein and an anti-cancer drug is reported. Bovine serum albumin (BSA) as a model protein was loaded into hydroxyapatite (HA) nanoparticles (NPs) and methotrexate (MTX) conjugated to poly(vinyl alcohol) was coated onto BSA-loaded HA NPs. Coating efficiency was in the range of 10-17 wt%. In vitro drug release showed that there was a steady increase in the release of both BSA and MTX with 76% of BSA and 88% of MTX being released in 13 days. Cytotoxicity studies of the NPs performed using human osteosarcoma (OMG-63) cell line showed the NPs were highly biocompatible and exhibited anti-proliferative activity in a concentration-dependent manner.

Development of Egg Shell Derived Carbonated Apatite Nanocarrier System for Drug Delivery.

Carbonated apatite has a chemical composition quite similar to biological apatite found in native bone. The incorporation of carbonate (CO2-3) ions groups into the apatitic crystal structure can tailor its crystallinity, solubility and biological activity that benefit the bone repair and regeneration. In this study, we report a simple and elegant method of synthesizing carbonated calcium deficient hydroxyapatite (ECCDHA) nanoparticles from egg shell wastes and its efficacy has been compared with synthetic calcium deficient hydroxyapatite (SCDHA) nanoparticles. Egg shell contains about 94% of calcium carbonate. Fourier transform infrared (FT-IR) spectroscopy results confirmed the carbonate substitution in the apatite as B-type and CHNS/O elemental analysis showed 6 wt.% of carbonate content in ECCDHA. Energy dispersive spectroscopy (EDS) analysis confirmed the presence of biologically relevant elements such as magnesium, strontium, fluoride, potassium etc., in ECCDHA inherited from the egg shell. In vitro cell culture studies confirmed that the ECCDHA is cellular compatible and it has enhanced cell adhesion and proliferation of L6 myoblast cells as compared to SCDHA. The potential of ECCDHA suitable for bone drug applications was tested with an antibiotic drug, doxycycline. The results showed higher drug loading and releasing for ECCDHA as compared to SCDHA during the period of study. Based on these results, the ECCDHA may be considered as a potential bone substitute and drug carrier system.

Electrospun 3D Scaffolds for Tissue Regeneration.

Tissue engineering aims to fabricate and functionalise constructs that mimic the native extracellular matrix (ECM) in the closest way possible to induce cell growth and differentiation in both in vitro and in vivo conditions. Development of scaffolds that can function as tissue substitutes or augment healing of tissues is an essential aspect of tissue regeneration. Although there are many techniques for achieving this biomimicry in 2D structures and 2D cell cultures, translation of successful tissue regeneration in true 3D microenvironments is still in its infancy. Electrospinning, a well known electrohydrodynamic process, is best suited for producing and functionalising, nanofibrous structures to mimic the ECM. A systematic control of the processing parameters coupled with novel process innovations, has recently resulted in novel 3D electrospun structures. This chapter gives a brief account of the various 3D electrospun structures that are being tried as tissue engineering scaffolds. Combining electrospinning with other 3D structure forming technologies, which have shown promising results, has also been discussed. Electrospinning has the potential to bridge the gap between what is known and what is yet to be known in fabricating 3D scaffolds for tissue regeneration.

Factors Affecting the Effective Management of Acute Stroke: A Prospective Observational Study.

BACKGROUND: Stroke, characterized by sudden loss of cerebral function, is among one of the leading cause of death and disability world over. The newer treatment modalities have changed the landscape of stroke treatment but are very much time bound. AIM: To characterize pre-hospital and in-hospital factors affecting acute stroke management thus defining lacunae in stroke management. SUBJECTS AND METHODS: A prospective observational study, conducted at the emergency department of a tertiary care center in southern India from August 2015 to July 2016. All stroke patients presenting within first 24 hours of onset were included. A pre -defined Knowledge-Attitude-Practice (KAP) questionnaire was used. RESULTS: Total of 133 patients were eligible out of which 28 were excluded for various reasons. Majority were >60 years age and male (61%). About 60% arrived within window. Distance from the hospital was one of the major factors for arrival within the window period. When compared by KAP questionnaire, bystanders of those arriving within window period had better awareness of stroke symptoms. CONCLUSIONS: Improving awareness of stroke symptoms and increasing availability of EMS is likely increase chances of stroke patients receiving appropriate acute management.

Electrospun Cytocompatible Polycaprolactone Blend Composite with Enhanced Wettability for Bone Tissue Engineering.

Electrospinning is recently used in tissue engineering due to their excellent ability to mimic the structure of extra cellular matrix (ECM), a prerequisite for creating an optimal microenvironment for cell growth. Electrospun nanofibrous composite scaffolds consisting of polycaprolactone (PCL)/Poly(1,4-butylene adipate-co-polycaprolactam) (PBAPCL) blend with hydroxyapatite (HA) have been fabricated to enhance the wettability and osseointegrative properties. Fourier transform-infrared spectroscopy (FT-IR) confirmed molecular interactions of the polymer blend along with the presence of HA. X-ray diffraction analysis (XRD) indicated semi-crystalline nature of the mat and also the presence of HA in the composite mat. The morphology of the fibres, were analyzed using scanning electron microscopy (SEM) and the diameter was found to be in the range of 400­600 nm. The composite fibers were of larger diameter compared to their polymer counterparts. Improved wettability of the electrospun composite mat has been observed by contact angle analysis. In vitro cell culture studies by Live/Dead assay and MTT using human osteosarcoma (HOS) cells indicated the cytocompatible nature of electrospun mat which was further confirmed by cell adhesion using SEM and Actin-phalloidin staining. Addition of PBAPCL and HA to PCL have a beneficial effect on cell growth and proliferation thereby making the composite, a prospective scaffold for bone tissue engineering applications.

Dentin remineralizing ability and enhanced antibacterial activity of strontium and hydroxyl ion co-releasing radiopaque hydroxyapatite cement.

Dental caries is an infection of the mineralized tooth structures that advances when acid secreted by bacterial action on dietary carbohydrates diffuses and dissolves the tooth mineral leading to demineralization. During treatment, clinicians often remove only the superficial infected tooth structures and retain a part of affected carious dentin to prevent excessive dentin loss and pulp exposure. Calcium hydroxide is used to treat the affected dentin because it is alkaline, induces pulp-dentin remineralization and decreases bacterial infection. Presence of strontium ions has also been reported to exhibit anticariogenic activity, and promote enamel and dentin remineralization. The objective of the present study was to develop novel hydroxyapatite cement from tetracalcium phosphate which gradually releases hydroxyl and strontium ions to exhibit antibacterial activity. Its potential to remineralize the dentin sections collected from extracted human molar tooth was studied in detail. The pH of all the experimental cements exhibited a gradual increase to ~10.5 in 10 days with 10% strontium substituted tetracalcium phosphate cement (10SC) showing the highest pH value which was sustained for 6 weeks. 10SC showed better antibacterial property against S. aureus and E. coli at the end of 1 week compared to other cements studied. It also exhibited the highest radiopacity equivalent to 4.8 mm of Al standard. 10SC treated dentin section showed better remineralization ability and highest elastic modulus. We can conclude that the hydroxyl and strontium ions releasing tetracalcium phosphate cement exhibits good antibacterial property, radiopacity and has the potential to encourage dentin remineralization.

Electrospun 3D composite scaffolds for craniofacial critical size defects.

Critical size defects in the craniofacial region can be effectively treated using three dimensional (3D) composite structures mimicking natural extra cellular matrix (ECM) and incorporated with bioactive ceramics. In this study we have shown that the dynamic liquid bath collector can be used to form electrospun polycaprolactone (PCL)-hydroxyapatite (HA) composite structure as unique 3D scaffold. The structure was found to have three distinct sections (base, stem and head) based on the mechanism of its formation and morphology. The size of the head portion was around 15 mm and was found to vary with the process parameters. Scanning electron microscopy (SEM) analysis revealed that the base had random fibres while the fibres in stem and head sections were aligned but perpendicular to each other. X-ray diffraction (XRD) analysis also showed an increase in the crystallinity index of the fibres from base to head section. Cytotoxicity and cytocompatibility studies using human osteosarcoma (HOS) cells showed good cell adhesion and proliferation indicating the suitability of the 3D structure for craniofacial graft applications.

Eggshell-Derived Hydroxyapatite: A New Era in Bone Regeneration.

BACKGROUND: Defects of maxillofacial skeleton lead to personal (functional and aesthetic), social and behavioral problems; which make the person to isolate from the main stream of society. So, bone regeneration is the need for proper structure, function, and aesthetics following cyst enucleation, trauma, and tumor ablative surgery; which helps for overall health of the individual. AIM AND OBJECTIVES: The preliminary study is planned to evaluate and compare the efficacy of eggshell-derived hydroxyapatite (EHA) and synthetic hydroxyapatite (SHA) following cystectomy. MATERIAL AND METHODS: Microwave-processed calcium deficient EHA and commercially available SHA are used for grafting. Total 20 patients enrolled in this study, consisting 10 in each group between 20 and 45 years of age. All the patients were evaluated for bone regeneration at first, second, third, and sixth month's interval, postsurgically, using radiovisiograph and clinical parameters. RESULTS: The bone formation characteristics vary at second month when compared to SHA. This difference may be because of the kinetics involved in the regeneration pattern. The pattern of bone healing was trabecular after third month, indicating complete bone formation. The study showed constant raise of density and remained same at the end of study period. CONCLUSIONS: Both EHA and SHA graft materials are equally efficient in early bone regeneration. Within the limitations of this study the EHA showed promising results. Which indicates the eggshell waste-bio mineral is worthwhile raw material for the production of HA and is a Go Green procedure. Eggshell-derived hydroxyapatite is economic, compared with SHA.

Nano-hydroxyapatite reinforced AZ31 magnesium alloy by friction stir processing: a solid state processing for biodegradable metal matrix composites.

Friction stir processing (FSP) was successfully adopted to fabricate nano-hydroxyapatite (nHA) reinforced AZ31 magnesium alloy composite as well as to achieve fine grain structure. The combined effect of grain refinement and the presence of embedded nHA particles on enhancing the biomineralization and controlling the degradation of magnesium were studied. Grain refinement from 56 to ~4 and 2 µm was observed at the stir zones of FSP AZ31 and AZ31-nHA composite respectively. The immersion studies in super saturated simulated body fluid (SBF 5×) for 24 h suggest that the increased wettability due to fine grain structure and nHA particles present in the AZ31-nHA composite initiated heterogeneous nucleation which favored the early nucleation and growth of calcium-phosphate mineral phase. The nHA particles as nucleation sites initiated rapid biomineralization in the composite. After 72 h of immersion the degradation due to localized pitting was observed to be reduced by enhanced biomineralization in both the FSPed AZ31 and the composite. Also, best corrosion behavior was observed for the composite before and after immersion test. MTT assay using rat skeletal muscle (L6) cells showed negligible toxicity for all the processed and unprocessed samples. However, cell adhesion was observed to be more on the composite due to the small grain size and incorporated nHA.

Functionally multifaceted alginate/curdlan/agarose-based bilayer fibro-porous dressings for addressing full-thickness diabetic wounds.

Full-thickness diabetic wounds are chronic injuries characterized by bleeding, excessive exude, and prolonged inflammation. Single-layer dressings fail to address their disturbed pathophysiology. Therefore, bilayer dressings with structural and compositional differences in each layer have gained attention. We hypothesized that natural polymer (alginate, curdlan, and agarose) based bilayer dressings with inherent healing properties could effectively resolve these issues. Hence, bilayer dressings were fabricated by electrospinning curdlan/agarose/ polyvinyl alcohol blend (top layer) on an alginate/agarose/polyvinyl alcohol-based lyophilized porous (bottom) layer. Ciprofloxacin was incorporated in both layers as a potential antibacterial drug. The bilayer dressing exhibited high swelling (~1300 %), biocompatibility (>90 % with NIH 3T3 and L929 mouse fibroblasts), and hemocompatibility (hemolysis <5 %). In vitro, scratch assay revealed a faster wound closure (~ 95-100 %) than control. Inhibition zone assay revealed antibacterial activity against Staphylococcus aureus and Escherichia coli. Real-time (in vitro) gene expression experiments performed using human THP-1 macrophages exhibited a significant increase in anti-inflammatory cytokines (4.51 fold in IL-10) and a decrease in pro-inflammatory cytokines (1.42 fold in IL-6) in comparison to lipopolysaccharide. Thus, fabricated dressings with high swelling, hemostatic, immunomodulatory, and antibacterial characteristics can serve as potential multifunctional and sustainable templates for healing full-thickness diabetic wounds.

Injectable macroporous naturally-derived apatite bone cement as a potential trabecular bone substitute.

In this study, we have formulated a novel apatite bone cements derived from natural sources (i.e. eggshell and fishbone) with improved qualities that is, porosity, resorbability, biological activity, and so forth. The naturally-derived apatite bone cement (i.e. FBDEAp) was prepared by mixing hydroxyapatite (synthesized from fishbone) and tricalcium phosphate (synthesized from eggshell) as a solid phase with a liquid phase (a dilute acidic blend of cement binding accelerator and biopolymers like gelatin and chitosan) with polysorbate (as liquid porogen) to get a desired bone cement paste. The prepared cement paste sets within the clinically acceptable setting time (≤20 min), easily injectable (>85%) through hands and exhibits physiological pH stability (7.3-7.4). The pure apatite phased bone cement was confirmed by x-ray diffraction and Fourier transform infrared spectroscopy analyses. The FBDEAp bone cement possesses acceptable compressive strength (i.e. 5-7 MPa) within trabecular bone range and is resorbable up to 28% in simulated body fluid solution within 12 weeks of incubation at physiological conditions. The FBDEAp is macroporous in nature (average pore size ~50-400 µm) with interconnected pores verified by SEM and micro-CT analyses. The FBDEAp showed significantly increased MG63 cell viability (>125% after 72 h), cell adhesion, proliferation, and key osteogenic genes expression levels (up to 5-13 folds) compared to the synthetically derived, synthetic and eggshell derived as well as synthetic and fishbone derived bone cements. Thus, we strongly believe that our prepared FBDEAp bone cement can be used as potential trabecular bone substitute in orthopedics.

Enhancing the degradation rate and biomineralization nature of antiferromagnetic Fe-20Mn alloy by groove pressing.

The Fe-Mn alloys are potential candidates for biodegradable implant applications. However, the very low degradation rates of Fe-Mn alloys in the physiological environment are a major disadvantage. In this study, the degradation rate of a Fe-20Mn alloy was improved using the groove pressing (GP) technique. Hot rolled sheets of 2 mm thickness were subjected to GP operation at 1000°C. Uniform fine-grained (UFG) Fe-Mn alloys were obtained using the GP technique. The influence of GP on the microstructure, mechanical properties, degradation behavior in simulated body fluid (SBF), surface wettability, biomineralization, and cytocompatibility was investigated and compared to the annealed (A Fe-Mn) and rolled (R Fe-Mn) sample. The groove-pressed Fe-Mn (G Fe-Mn) alloy had a grain size of approximately 40 ± 16 µm whereas the A Fe-Mn and R Fe-Mn samples had grain sizes of 303 ± 81 and 117 ± 14.5 µm, respectively. Enhanced strength and elongation were also observed with the G Fe-Mn sample. The potentiodynamic polarization test showed the highest Icorr, lowest polarization resistance, and lowest Ecorr for the G Fe-Mn sample among all other samples indicating its higher degradation rate. The weight loss data from immersion tests also shows that the percentage of weight loss increases with time indicating the accelerated degradation behavior of the sample. The static immersion test showed an enhancement in weight loss of 0.46 ± 0.02% and 1.02 ± 0.05% for R Fe-Mn and G Fe-Mn samples, respectively, than A Fe-Mn sample (0.31 ± 0.03%) after 56 days in immersion in SBF. The greater biomineralization tendency in UFG materials is confirmed by the G Fe-Mn sample's stronger hydroxyapatite deposition. When compared to the A Fe-Mn and R Fe-Mn samples, the G Fe-Mn sample has a better wettability, which promotes higher cell adhesion and vitality, showing higher biocompatibility. This study demonstrates that Fe-20Mn processed by GP has potential applications for the manufacture of biodegradable metallic implants.

Fabrication and evaluation of agarose-curdlan blend derived multifunctional nanofibrous mats for diabetic wounds.

Diabetic wounds with complex pathophysiology significantly burden the wound care industry and require novel management strategies. In the present study, we hypothesized that agarose-curdlan based nanofibrous dressings could be an effective biomaterial for addressing diabetic wounds due to their inherent healing properties. Hence, agarose/curdlan/polyvinyl alcohol based nanofibrous mats loaded with ciprofloxacin (0, 1, 3, and 5 wt%) were fabricated using an electrospinning technique with water and formic acid. In vitro evaluation revealed the average diameter of the fabricated nanofibers between 115 and 146 nm with high swelling (~450-500 %) properties. They exhibited enhanced mechanical strength (7.46 ± 0.80 MPa -7.79 ± 0.007 MPa) and significant biocompatibility (~90-98 %) with L929 and NIH 3T3 mouse fibroblasts. In vitro scratch assay showed higher proliferation and migration of fibroblasts (~90-100 % wound closure) compared to electrospun PVA and control. Significant antibacterial activity was observed against Escherichia coli and Staphylococcus aureus. In vitro real-time gene expression studies with human THP-1 cell line revealed a significant downregulation of pro-inflammatory cytokines (8.64 fold decrease for TNF-α) and upregulation of anti-inflammatory cytokines (6.83 fold increase for IL-10) compared to lipopolysaccharide. In brief, the results advocate agarose-curdlan mat as a potential multifunctional, bioactive, and eco-friendly dressing for healing diabetic wounds.

Fabrication of injectable antibiotic-loaded apatitic bone cements with prolonged drug delivery for treating post-surgery infections.

Antibiotic-loaded bioactive bone substitutes are widely used for treating various orthopedic diseases and prophylactically to avoid post implantation infection. Calcium deficient hydroxyapatite (also known as apatitic bone cement) is a potential bioactive bone substitute in orthopedics due to its chemical composition similar to that of natural bone minerals. In this study, fabrication of mannitol (a solid porogen) incorporated injectable synthetic (Syn) and eggshell derived (ESD) apatitic bone cements loaded with antibiotics (gentamicin/meropenem/ rifampicin/vancomycin) was investigated. The release kinetics of the antibiotics were studied by fitting them with different kinetic models. All the antibiotics-loaded apatitic bone cements set within clinically accepted setting time (20 ± 2 min) and with good injectability (>70%). The antibiotics released from these bone cements were found to be controlled and sustained throughout the study time. Weibull and Gompertz (applies in least initial burst and sustain drug release rate models) were the best models to predict the release behavior. They cements had acceptable compressive strength (6-10 MPa; in the range of trabecular bone) and were biodegradable (21%-27% within 12 weeks of incubation) in vitro in simulated body fluids at physiological conditions. These bone cements showed excellent antibacterial activity from day 1 onwards and no bacterial colony was found from day 3 onwards. The viability of MG63 cells in vitro after 72 h was significantly higher after 24 h (i.e., ~110%). The cells were well attached and spread over the surface of the cements with extended morphology. The ESD antibiotic-loaded apatitic bone cements showed better injectability, degradation and cytocompatibility compared when compared to Syn antibiotic-loaded apatitic bone cements. Thus, we believe that the ESD antibiotic-loaded apatitic bone cements are suitable as potential injectable bone substitutes to avoid post-operative implant associated and other acute or chronic bone infections.

Perspectives of nanofibrous wound dressings based on glucans and galactans - A review.

Wound healing is a complex and dynamic process that needs an appropriate environment to overcome infection and inflammation to progress well. Wounds lead to morbidity, mortality, and a significant economic burden, often due to the non-availability of suitable treatments. Hence, this field has lured the attention of researchers and pharmaceutical industries for decades. As a result, the global wound care market is expected to be 27.8 billion USD by 2026 from 19.3 billion USD in 2021, at a compound annual growth rate (CAGR) of 7.6 %. Wound dressings have emerged as an effective treatment to maintain moisture, protect from pathogens, and impede wound healing. However, synthetic polymer-based dressings fail to comprehensively address optimal and quick regeneration requirements. Natural polymers like glucan and galactan-based carbohydrate dressings have received much attention due to their inherent biocompatibility, biodegradability, inexpensiveness, and natural abundance. Also, nanofibrous mesh supports better proliferation and migration of fibroblasts because of their large surface area and similarity to the extracellular matrix (ECM). Thus, nanostructured dressings derived from glucans and galactans (i.e., chitosan, agar/agarose, pullulan, curdlan, carrageenan, etc.) can overcome the limitations associated with traditional wound dressings. However, they require further development pertaining to the wireless determination of wound bed status and its clinical assessment. The present review intends to provide insight into such carbohydrate-based nanofibrous dressings and their prospects, along with some clinical case studies.

Biomimetic ion substituted and Co-substituted hydroxyapatite nanoparticle synthesis using Serratia Marcescens.

Biomimicry is becoming deep-rooted as part of bioceramics owing to its numerous functional advantages. Naturally occurring hydroxyapatite (HA) apart from primary nano structures are also characterised by various ionic substitutions. The ease of accommodating such key elements into the HA lattice is known to enhance bone healing properties of bioceramics. In this work, hydroxyapatite synthesized via biomimetic approach was substituted with individual as well as multiple cations for potential applications in bone repair. Ion substitutions of Sr, Mg and Zn was carried out on HA for the first time by using Serratia grown in a defined biomineralization medium. The individual ions of varying concentration substituted in Serratia HA (SHA) (Sr SHA, Mg SHA and Zn SHA) were analysed for crystallinity, functional groups, morphology and crystal size. All three showed decreased crystallinity, phase purity, large agglomerated aggregates and needle-shaped morphologies. Fourier transform infrared spectroscopy (FTIR) spectra indicated increased carbonate content of 5.8% resembling that of natural bone. Additionally, the reduced O-H intensities clearly portrayed disruption of HA lattice and subsequent ion-substitution. The novelty of this study lies primarily in investigating the co-substitution of a combination of 1% Sr, Zn and Mg in SHA and establishing the associated change in bone parameters. Scanning electron microscope (SEM) and transmission electron microscope (TEM) images clearly illustrated uniform nano-sized agglomerates of average dimensions of 20-50 nm length and 8-15 nm width for Sr SHA; 10-40 nm length and 8-10 nm width for both Zn SHA and Mg SHA and 40-70 nm length and 4-10 nm width in the case of 1% Sr, Zn, Mg SHA. In both individual as well as co-substitutions, significant peak shifts were not observed possibly due to the lower concentrations. However, cell volumes increased in both cases due to presence of Sr2+ validating its dominant integration into the SHA lattice. Rich trace ion deposition was presented by energy dispersive X-ray spectroscopy (EDS) and quantified using inductively coupled plasma optical emission spectrometer (ICP-OES). In vitro cytotoxicity studies in three cell lines viz. NIH/3T3 fibroblast cells, MG-63 osteosarcoma cells and RAW 264.7 macrophages showed more than 90% cell viability proving the biocompatible nature of 1% Sr, Zn and Mg in SHA. Microbial biomineralization by Serratia produced nanocrystals of HA that mimicked "bone-like apatite" as evidenced by pure phase, carbonated groups, reduced crystallinity, nano agglomerates, variations in cell parameters, rich ion deposition and non-toxic nature. Therefore ion-substituted and co-substituted biomineralized nano SHA appears to be a suitable candidate for applications in biomedicine addressing bone injuries and aiding regeneration as a result of its characteristics close to that of the human bone.