Despite bone's impressive ability to heal after traumatic injuries and fractures, a significant need still exists for developing strategies to promote healing of nonunion defects. To address this issue, we developed collagen-based hydrogels containing two-dimensional nanosilicates. Nanosilicates are ultrathin nanomaterials with a high degree of anisotropy and functionality that results in enhanced surface interactions with biological entities compared to their respective three-dimensional counterparts. The addition of nanosilicates resulted in a 4-fold increase in compressive modulus along with an increase in pore size compared to collagen-based hydrogels. In vitro evaluation indicated that the nanocomposite hydrogels are capable of promoting osteogenesis in the absence of any osteoinductive factors. A 3-fold increase in alkaline phosphatase activity and a 4-fold increase in the formation of a mineralized matrix were observed with the addition of the nanosilicates to the collagen-based hydrogels. Overall, these results demonstrate the multiple functions of nanosilicates conducive to the regeneration of bone in nonunion defects, including increased network stiffness and porosity, injectability, and enhanced mineralized matrix formation in a growth-factor-free microenvironment.

Although hydrogels are able to mimic native tissue microenvironments, their utility for biomedical applications is severely hampered due to limited mechanical stiffness and low toughness. Despite recent progress in designing stiff and tough hydrogels, it is still challenging to achieve a cell-friendly, high modulus construct. Here, we report a highly efficient method to reinforce collagen-based hydrogels using extremely low concentrations of a nanoparticulate-reinforcing agent that acts as a cross-link epicenter. Extraordinarily, the addition of these nanoparticles at a 10 000-fold lower concentration relative to polymer resulted in a more than 10-fold increase in mechanical stiffness and a 20-fold increase in toughness. We attribute the high stiffness of the nanocomposite network to the chemical functionality of the nanoparticles, which enabled the cross-linking of multiple polymeric chains to the nanoparticle surface. The mechanical stiffness of the nanoengineered hydrogel can be tailored between 0.2 and 200 kPa simply by manipulating the size of the nanoparticles (4, 8, and 12 nm), as well as the concentrations of the nanoparticles and polymer. Moreover, cells can be easily encapsulated within the nanoparticulate-reinforced hydrogel network, showing high viability. In addition, encapsulated cells were able to sense and respond to matrix stiffness. Overall, these results demonstrate a facile approach to modulate the mechanical stiffness of collagen-based hydrogels and may have broad utility for various biomedical applications, including use as tissue-engineered scaffolds and cell/protein delivery vehicles.

Nanoparticle shape has emerged as a key regulator of nanoparticle transport across physiological barriers, intracellular uptake, and biodistribution. We report a facile approach to synthesize ellipsoidal nanoparticles through self-assembly of poly(glycerol sebacate)-co-poly(ethylene glycol) (PGS-co-PEG). The PGS-PEG nanoparticle system is highly tunable, and the semiaxis length of the nanoparticles can be modulated by changing PGS-PEG molar ratio and incorporating therapeutics. As both PGS and PEG are highly biocompatible, the PGS-co-PEG nanoparticles show high hemo-, immuno-, and cytocompatibility. Our data suggest that PGS-co-PEG nanoparticles have the potential for use in a wide range of biomedical applications including regenerative medicine, stem cell engineering, immune modulation, and cancer therapeutics. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2048-2058, 2018.

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Peptide receptor radionuclide therapy is used to treat solid tumors by locally delivering radiation. However, due to nephro-and hepato-toxicity, it is limited by its dosage. To amplify radiation damage to tumor cells, radiolabeled nanogels can be used. We show that by tuning the mechanical properties of nanogels significant enhancement in circulation half-life of the gel could be achieved. We demonstrate why and how small changes in the mechanical properties of the nanogels influence its cellular fate. Nanogels with a storage modulus of 37 kPa were minimally phagocytosed by monocytes and macrophages compared to nanogels with 93 kPa modulus. Using PET/CT a significant difference in the blood circulation time of the nanogels was shown. Computer simulations affirmed the results and predicted the mechanism of cellular uptake of the nanogels. Altogether, this work emphasizes the important role of elasticity even for particles that are inherently soft such as nano-or microgels.

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Superparamagnetic FeAs nanoparticles with a fairly high blocking temperature (T B) have been synthesized through a hot injection precipitation technique. The synthesis involved usage of triphenylarsine (TPA) as the As precursor, which reacts with Fe(CO)5 by ligand displacement at moderate temperatures (300 °C). Addition of a surfactant, hexadecylamine (HDA), assists in the formation of the nanoparticles, due to its coordinating ability and low melting point which provides a molten flux like condition making this synthesis a solventless method. Decomposition of the carbonaceous precursors, HDA, TPA and Fe(CO)5, also produces the carbonaceous shell coating the FeAs nanoparticles. Magnetic characterization of these nanoparticles revealed the superparamagnetic nature of these nanoparticles with a perfect anhysteretic nature of the isothermal magnetization above T B. The T B observed in this system was indeed high (240 K) when compared with other superparamagnetic systems conventionally utilized for magnetic storage devices. It could be further increased by decreasing the strength of the applied magnetic field. The narrow hysteresis with low magnitude of coercivity at 5 K suggested soft ferromagnetic ordering in these nanoparticle ensembles. Mössbauer and XPS studies indicated that the Fe was present in +3 oxidation state and there was no signature of Fe(0) that could have been responsible for the increased magnetic moment and superparamagnetism. Typically for superparamagnetic nanoparticle ensemble, the need for isolation of the superparamagnetic domains (thereby inhibiting particle aggregation and enhancing the T B) has been in constant limelight. Carbonaceous coating on these as-synthesized nanoparticles formed in situ provided the physical nonmagnetic barrier needed for such isolation. The high T B and room temperature magnetic moment of these FeAs@C nanoparticles also make them potentially useful for applications in ferrofluids and magnetic refrigeration. In principle this method can be used as a general route toward synthesis of other arsenide nanostructures including the transition metal arsenide which show interesting magnetic and electronic properties (e.g., CoAs, MnAs) with finer control over morphology, composition and structure.

Endogenous targeted radiotherapy is emerging as an integral modality to treat a variety of cancer entities. Nevertheless, despite the positive clinical outcome of the treatment using radiolabeled peptides, small molecules, antibodies, and nanobodies, a high degree of hepatotoxicity and nephrotoxicity still persist. This limits the amount of dose that can be injected. In an attempt to mitigate these side effects, the use of nanocarriers such as nanoparticles (NPs), dendrimers, micelles, liposomes, and nanogels (NGs) is currently being explored. Nanocarriers can prolong circulation time and tumor retention, maximize radiation dosage, and offer multifunctionality for different targeting strategies. In this review, the authors first provide a summary of radiation therapy and imaging and discuss the new radiotracers that are used preclinically and clinically. They then highlight and identify the advantages of radio‐nanomedicine and its potential in overcoming the limitations of endogenous radiotherapy. Finally, the review points to the ongoing efforts to maximize the use of radio‐nanomedicine for efficient clinical translation.