Type 2 diabetes mellitus (T2DM) commonly affects the bone mineral phase and advanced glycation end-products (AGEs) which eventually led to changes in bone material properties on the nano and macro-scale. Several anti-diabetic compounds are widely used to control high blood sugar or glucose caused by T2DM. Low Dose Naltrexone (LDN), an opiate receptor antagonist, and a known TLR4 antagonist, treatment can improve glucose tolerance and insulin sensitivity in high-fat-diet (HFD) induced T2DM mice. However, the influences of LDN on the local bone quality, mineralization of the bone, and the skeletal AGEs levels have not been fully elucidated. The objective of this study is to understand the effect of LDN on Raman assisted bone quality, skeletal AGEs (determined by Raman spectroscopy), and nano-mechanical properties in HFD induced T2DM mice bone. In order to investigate these, mice and corresponding bones were divided into four groups (divided based on diet and treatment), (a) normal control diet treated with saline water, (b) normal control diet treated with LDN, (c) HFD treated with saline water, and (d) HFD treated with LDN. In T2DM condition (HFD treated with saline water), alteration of Raman-based compositional measures in bone quality including mineral-to-matrix ratios, carbonate substitution, mineral crystallinity, and collagen quality was observed. Our data also indicated that T2DM enhances the skeletal AGEs, and impairs the nano-mechanical properties. Interestingly, present results indicated that LDN controls the Raman-based compositional measures in bone quality in HFD induced T2DM mice bone. Additionally, LDN also protects the alteration of the skeletal AGEs levels and nano-mechanical properties in T2DM mice bone. This study concluded that LDN can control the HFD induced T2DM affected bone abnormalities at multiple hierarchical levels.A truly bioinspired approach to design optimization should follow the energetically favorable natural paradigm of "minimum inventory with maximum diversity". This study was inspired by constructive regression of trabecular bone - a natural process of network connectivity optimization occurring early in skeletal development. During trabecular network optimization, the original excessively connected network undergoes incremental pruning of redundant elements, resulting in a functional and adaptable structure operating at lowest metabolic cost. We have recapitulated this biological network topology optimization algorithm by first designing in silico an excessively connected network in which elements are dimension-independent linear connections among nodes. Based on bioinspired regression principles, least-loaded connections were iteratively pruned upon simulated loading. Evolved networks were produced along this optimization trajectory when pre-set convergence criteria were met. These biomimetic networks were compared to each other, and to the reference network derived from mature trabecular bone. Our results replicated the natural network optimization algorithm in uniaxial compressive loading. However, following triaxial loading, the optimization algorithm resulted in lattice networks that were more stretch-dominated than the reference network, and more capable of uniform load distribution. As assessed by 3D printing and mechanical testing, our heuristic network optimization procedure opens new possibilities for parametric design.Different bioinks have been used to produce cell-laden alginate-based hydrogel constructs for cell replacement therapy but some of these approaches suffer from issues with print quality, long-term mechanical instability, and bioincompatibility. In this study, new alginate-based bioinks were developed to produce cell-laden grid-shaped hydrogel constructs with stable integrity and immunomodulating capacity.  https://www.selleckchem.com/products/l-arginine-l-glutamate.html  Integrity and printability were improved by including the co-block-polymer Pluronic F127 in alginate solutions. To reduce inflammatory responses, pectin with a low degree of methylation was included and tested for inhibition of Toll-Like Receptor 2/1 (TLR2/1) dimerization and activation and tissue responses under the skin of mice. The viscoelastic properties of alginate-Pluronic constructs were unaffected by pectin incorporation. The tested pectin protected printed insulin-producing MIN6 cells from inflammatory stress as evidenced by higher numbers of surviving cells within the pectin-containing construct following exposure to a cocktail of the pro-inflammatory cytokines namely, IL-1β, IFN-γ, and TNF-α. The results suggested that the cell-laden construct bioprinted with pectin-alginate-Pluronic bioink reduced tissue responses via inhibiting TLR2/1 and support insulin-producing β-cell survival under inflammatory stress. Our study provides a potential novel strategy to improve long-term survival of pancreatic islet grafts for Type 1 Diabetes (T1D) treatment.Stent implantation has become one of the most widely used methods for the treatment of cardiovascular diseases. However, endothelial dysfunction and abnormal inflammatory response following implantation may lead to delayed re-endothelialization, resulting in vascular restenosis and stent thrombus. To address the concerns, we constructed nanospindles composed of TiO2 and Ti4Ni2O through hydrothermal treatment of amorphous Ni-Ti-O nanopores anodically grown on NiTi alloy. The results show the treatment can significantly improve hydrophilicity and reduce Ni ion release, essentially independent of hydrothermal duration. The nanospindle surfaces not only promote the expression of endothelial functionality but also activate macrophages to induce a favorable immune response, downregulate pro-inflammatory M1 markers and upregulate pro-healing M2 markers. Moreover, nitric oxide (NO) synthesis, VEGF secretion, and migration of endothelial cells are enhanced after cultured in macrophage conditioned medium. The nanospindles thus are promising as vascular stent coatings to promote re-endothelization.Biomaterials based on bioactive glass with gold nanoparticle composites have many applications in tissue engineering due to their tissue regeneration and angiogenesis capacities. The objectives of the study were to develop new composites using bioactive glass with gold nanospheres (BGAuSP) and gold nanocages (BGAuIND), individually introduced in alginate-pullulan (Alg-Pll) polymer, to evaluate their biocompatibility potential, and to compare the obtained results with those achieved when β-tricalcium phosphate-hydroxyapatite (βTCP/HA) replaced the BG. The novel composites underwent structural and morphological characterization followed by in vitro viability testing on fibroblast and osteoblast cell lines. Additionally, the biomaterials were subcutaneously implanted in Sprague Dawley rats, for in vivo biocompatibility assessment during 3 separate time frames (14, 30 and 60 days). The biological effects were evaluated by histopathology and immunohistochemistry. The physical characterization revealed the cross-linking between polymers and glasses/ceramics and demonstrated a suitable thermal stability for sterilization processes.