Can the venerated silk be the next generation nanobiomaterialfor biomedical device designing, regenerative medicine and drugdelivery? Prospects and hitches

Of late, the relevance of silk in a myriad of material science and biotechnological realms has been realized, as attested by the incessantly clambering number of reports and patents in the scienti fic repositories. The write-up is geared off with a scrutiny into the pertinence of the basic nano-structural features of silk, christened as the ‘queen of textile’ for exemplary bioengi- neering applications including designing and fabrication of devices for micro fluidics, opto fluidics, chemo/bio sensing, etc. Then, the major thrust of this short review is directed towards comprehending the prospects of using silk-based biomaterials (e.g. sca ffolds, electrospun membranes, films, hydrogels, bioinks) for tissue engineering and regenerative medicine as well as targeted delivery of various biomolecular cargoes/therapeutic agents, etc., as vouched by few avant-garde endeavours of the recent years. The write-up is entwined with a discussion on the various factors that could plausibly hinder the realization of silk as the next-generation nanobiomaterial, suggestions for some approaches to dodge and deal with the practical snags and what lies ahead!

Molecular Modeling of Cell Adhesion Peptides on Hydroxyapatite and TiO₂Surfaces: Implication in Biomedical Implant Devices

Molecular modeling as a tool in studying peptide-substrate interactions provides insight on peptide adsorption conformation, adsorption energy, and stability of the peptide-inorganic interface. This work investigates the hydration and interaction of cell-adhesion peptides, specifically RGD and YIGSR, with the hydroxyapatite surface and TiO2 surface in cluster and periodic boundary condition approaches. The comparison of adsorption energies of RGD and YIGSR on both Hydroxyapatite (HA) and TiO2 surfaces reveals the similarities in adsorption energy and orientation pattern of peptides on both surfaces. The models demonstrate that initial peptide orientation affects adsorption energy for both. YIGSR is consistently more strongly adsorbed to HA-(001) surfaces and steps than RGD for both the surfaces. In addition, RGD maintained its “hairpin”-like structure during adsorption on a flat HA-(001) surface, and a slightly “relaxed hairpin” structure on TiO2 (110) surface. Adsorption energies of RGD on TiO2 (110) surface are significantly more favorable compared to HA-(001) surface, suggesting potential role of TiO2 as biomedical implants when tissue regeneration occurs via cell signaling.

Purification of Nanoparticles by Liquid Chromatography for Biomedical and Engineering Applications

Nanoparticles are extensively used for various applications in science, engineering and medicine. Synthesis of nanoparticles with high purity is essential to utilize the same in different fields of science and technology. In the present study, liquid chromatography is utilized to purify the nanoparticles. Predominantly, gold nanoparticles were synthesized from gold auric cholide and preserved in phosphate or citrate buffer. A method to purify gold nanoparticles is essential because of the possible interference from gold auric chloride and other impurities in buffer. Herein, a method has been developed using high performance liquid chromatography to purify gold nanoparticles with 100 nm in size from gold auric chloride and residues. UV-Vis spectroscopy was also done to ascertain the purity of the nanoparticles.

Nanocomposites and bone regeneration

This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite （HA） and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA （reduced grain size）, one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/ healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

Osteogenic and antibacterial dual functions of a novel levofloxacin loaded mesoporous silica microspheres/nano-hydroxyapatite/ polyurethane composite scaffold

Lev/MSNs/n-HA/PU has been proved to be a novel scaffold material to treat bone defect caused by chronic osteomyelitis.We have previously identified that this material can effectively treat chronic osteomyelitis caused by Staphylococcus aureus in vivo.However,the potential mechanisms of antibacterial and osteogenic induction properties remain unclear.Thus,for osteogenesis property,immunohistochemistry,PCR,and Western blot were performed to detect the expression of osteogenic markers.Furthermore,flow cytometry and TUNEL were applied to analyze MC3T3-E1 proliferation and apoptosis.For antibacterial property,the material was co-cultivated with bacteria,bacterial colony forming units was counted and the release time of the effective levofloxacin was assayed by agar disc-diffusion test.Moreover,scanning electron microscope was applied to observe adhesion of bacteria.In terms of osteogenic induction,we found BMSCs adherently grew more prominently on Lev/MSNs/n-HA/PU.Lev/MSNs/n-HA/PU also enhanced the expression of osteogenic markers including OCN and COL1a1,as well as effectively promoted the transition from G1 phase to G2 phase.Furthermore,Lev/MSNs/n-HA/PU could reduce apoptosis of MC3T3-E1.Besides,both Lev/MSNs/n-HA/PU and n-HA/PU materials could inhibit bacterial colonies,while Lev/MSNs/n-HA/PU possessed a stronger antibacterial activities,and lower bacterial adhesion than n-HA/PU.These results illustrated that Lev/MSNs/n-HA/PU composite scaffold possess favorable compatibility in vitro,which induce osteogenic differentiation of MSCs,promote proliferation and differentiation of MC3T3-E1,and inhibit apoptosis.Moreover,clear in vitro antibacterial effect of Lev/MSNs/n-HA/PU was also observed.In summary,this study replenishes the potential of Lev/MSNs/n-HA/PU composite scaffold possess dual functions of anti-infection and enhanced osteogenesis for future clinical application.

Properties of carbon nanotube-dispersed Sr-hydroxyapatite injectable material for bone defects

This study concerns the synthesis of gel materials based on carbon nanotubes dispersed strontium-modified hydroxyapatite(Sr-HA)at different compositions obtained by sol–gel technology and their influence on human-bone-marrow-derived mesenchymal stem cells.Furthermore,an evaluation of the influence of nanotubes and Strontium on physico-chemical,morphological,rheological and biological properties of hydroxyapatite gel was also performed.Morphological analysis(scanning electron microscopy)shows a homogeneous distribution of modified nanotubes in the ceramic matrix improving the bioactive properties of materials.The biological investigations proved that Sr-HA/carbon nanotube gel containing 0–20 mol(%)of Sr showed no toxic effect and promote the expression of early and late markers of osteogenic differentiation in cell culture performed in basal medium without osteogenic factors.Finally,the SrHA/carbon nanotube gels could have a good potential application as filler in bone repair and regeneration and may be used in the osteoporotic disease treatment.

Nanofiber–microsphere (nano-micro) matrices for bone regenerative engineering: a convergence approach toward matrix design

Bone is an essential organ for health and quality of life.Due to current shortfalls in therapy for bone tissue engineering,scientists have sought the application of synthetic materials as bone graft substitutes.As a composite organic/inorganic material with significant extra cellular matrix(ECM),one way to improve bone graft substitutes may be to engineer a synthetic matrix that is influenced by the physical appearance of natural ECM networks.In this work,the authors evaluate composite,hybrid scaffolds for bone tissue engineering based on composite ceramic/polymer microsphere scaffolds with synthetic ECM-mimetic networks in their pore spaces.Using thermally induced phase separation,nanoscale fibers were deposited in the pore spaces of structurally sound microsphere-based scaffold with a density proportionate to the initial polymer concentration.Porosimetry and mechanical testing indicated no significant changes in overall pore characteristics or mechanical integrity as a result of the fiber deposition process.These scaffolds displayed adequate mechanical integrity on the scale of human trabecular bone and supported the adhesion and proliferation of cultured mouse calvarial osteoblasts.Drawing from natural cues,these scaffolds may represent a new avenue forward for advanced bone tissue engineering scaffolds.

The challenge to improve the response of biomaterials to the physiological environment

New applications of biomaterials often require advanced structures containing synthetic and natural components that are tuned to provide properties unique to a specific application.We discuss how structural characteristics of biomaterials,especially hydrophilic ones,can be used in conjunction with non-ideal thermodynamics to develop advanced medical systems.We show a number of examples of biocompatible,intelligent biomaterials that can be used for organ replacement,biosensors,precise drug delivery over days or weeks,and regenerative medicine.

Immunomodulatory nanodiamond aggregate-based platform for the treatment of rheumatoid arthritis

We previously demonstrated that octadecylamine-functionalized nanodiamond(ND-ODA)and dexamethasone(Dex)-adsorbed ND-ODA(ND-ODA–Dex)promoted anti-inflammatory and proregenerative behavior in human macrophages in vitro.In this study,we performed a pilot study to investigate if these immunomodulatory effects translate when used as a treatment for rheumatoid arthritis in mice.Following local injection in limbs of mice with collagen type II-induced arthritis,microcomputed tomography showed that mice treated with a low dose of ND-ODA and ND-ODA–Dex did not experience bone loss to the levels observed in non-treated arthritic controls.A low dose of ND-ODA and ND-ODA–Dex also reduced macrophage infiltration and expression of proinflammatory mediators iNOS and tumor necrosis factor-a compared to the arthritic control,while a high dose of ND-ODA increased expression of these markers.Overall,these results suggest that ND-ODA may be useful as an inherently immunomodulatory platform,and support the need for an in-depth study,especially with respect to the effects of dose.

Engineering advanced dynamic biomaterials to optimize adoptive T-cell immunotherapy

Adoptive T-cell therapy(ACT)is a promising therapeutic approach based on the concept of potent T-cell mediated immunity against the tumor.The outcome of antigen-specific T-cells responses relies on the interaction between T-cells and antigen-presenting cells,which provides signals for generating different T-cell phenotypes with different roles in tumor removal.However,such interaction is often not optimal in vivo and results in low therapeutic efficacy.To reach the full potential of the T-cell response,current research put effort into developing dynamic biomaterials as artificial antigen-presenting cells to study and regulate the T-cell activity for controlling T-cell fate.In this perspective,we provide(1)an overview of ACT and general T-cells behaviors,(2)explore the insight on how biomaterials can be used for studying and regulating T-cell behaviors,(3)and discuss conceptual gaps in knowledge for biomaterials-based immunotherapy.

Facile synthesis of nano-sized CuFe2S3:morphology and diverse functional tuning and crystal growth mechanism exploring

Ternary chalcogenide compounds are such promising and have been used for much practical applications.As a sort of these compounds,cubanite(CuFe2S3)possess some unique properties which can be used in different fields.In our study,we developed a facile one pot synthesis of CuFe2S3 nanocrystals(NCs)at a low reaction temperature,and achieved a morphology and phase composition tuning of the NCs through changing a variety of precursors and surfactants,meanwhile improved their magnetism and optical properties.Eventually,well-ordered and‘nano-brick’like CuFe2S3 NCs were obtained and showed best magnetism and near-infrared fluorescence properties.Furthermore,the NCs were proved with good biocompatibility and possibility for cell labeling.This kind of materials with lower toxicity and potential of magnetic is bound to remedy the defects of photoluminescence quantum dots(QDs)and be with higher potential in the field of biological diagnosis and multi-functional system construction.

Nanotechnology applications in osteodistraction

Most current strategies for bone regeneration have relatively satisfactory results.However,there are drawbacks and limitations associated with their use and availability,and even controversial reports about their efficacy and cost-effectiveness.The induction of new bone formation through distraction osteogenesis(DO)is widespread clinical application in the treatment of bone defects,limb deformities,and fracture nonunions.However,a lengthy period of external fixation is usually needed to allow the new bone to consolidate,and complications such as refracture at the distraction gap often occur.Although various biomaterials have been used as injectable delivery systems in DO models,little has been reported on the use of nanobiomaterials as carrier materials for the sustained release of growth factors in bone regeneration.One area of focus in nanotechnology is the delivery of osteogenic factors in an attempt to modulate the formation of bone.This review article seeks to demonstrate the potential of nanobiomaterials to improve biological applications pertinent to osteodistraction.