infections, and biochemical disorders could be addressed with a wide variety of bone substitutes or implants. [1] Bone is a mineralized composite of inorganic and organic units, mostly hydroxyapatite (HA) and type I collagen, respectively. [2] To mimic the nature of bone, scientists have researched several aspects of the biomaterials of bone substitutes or implants over the past decades, [3] and chemical composition of them is a primary consideration. Currently, magnesium (Mg 2+ ) and Mg 2+ alloys are gaining increasing research interest due to their promising merits, such as biodegradability, relatively slow corrosion rates, and suitable mechanical properties. [4] However, the osteoinductive effect of Mg 2+ alloys could not be directly determined due to complex alloy constituents, complicated surface modification technology, and intricate physiological microenvironments.A bone mineral precursor, amorphous calcium phosphate (ACP), could be fabricated with Mg 2+ ions, which act as an ACP phase stabilizer to maintain a noncrystal phase. [5] Mg 2+ could partially substitute Ca 2+ ions in the apatite structure and inhibit ACP transformation into HA. [5a] Chemically, it has been shown that Mg 2+ ions retard the crystallization of ACP and control the final aging of crystals. [5c] Moreover, Mg 2+ is considered the main intracellular antagonist of Ca 2+ . [6] Hence, there is an unreasonable paradox that Mg 2+ exerts its role during bone formation as an indispensable element due to its inhibitory effects on biomineralization, which were ignored by previous studies. [6,7] Thus, logically, Mg 2+ is proposed to have a complicated connection with osteogenesis.To answer this question derived from the field of regenerative and bioengineering medicine, the best approach is to investigate development, which could subsequently guide regeneration. [2,8] Mineralization development is a kind of complex chemical reaction among calcium (Ca 2+ ), phosphate (PO 4 3− ), Mg 2+ , and some amino acids. [2] Among the bones in vertebrates, the cranial bone is unique because it provides spaces, support, and protection for soft brain tissues, and has two different developmental mechanisms, namely, endochondral and intramembranous ossification. [9] Therefore, the development of the skull is a proper model. [10] Numerous studies have demonstrated that several kinds of factors play explicit roles during cranial development, [8,9,11] but which elements and how these elements influence the formation and mineralization of the skull, in particular, HA and type I collagen, are not well defined.Magnesium (Mg 2+ ), as a main component of bone, is widely applied to promote bone growth and regeneration. However, Mg 2+ can chemically inhibit the crystallization of amorphous calcium phosphate into hydroxyapatite (HA). The underlying mechanisms by which Mg 2+ improves bone biomineralization remain elusive. Here, it is demonstrated that Mg 2+ plays dual roles in bone biomineralization from a developmental perspective. During embryonic development, the Mg 2+ ...

T cell immunotherapy holds significant challenges in solid tumors, mainly due to the T cells’ low activation and the decreased synthesis–release of therapeutic proteins, including perforin and granzyme B, which are present in lysosomes. In this study, a lysosome‐targeting nanoparticle (LYS‐NP) is developed by way of a mineralized metal–organic framework (MOF) coupled with a lysosome‐targeting aptamer (CD63‐aptamer) to enhance the antitumor effect of T cells. The MOF synthesized from Zn2+ and dimethylimidazole has good protein encapsulation and acid sensitivity, and is thus an ideal lysosomal delivery vector. Calcium carbonate (CaCO3) is used to induce MOF mineralization, improve the composite material's stability in encapsulating therapeutic protein, and provide calcium ions with synergistic effects. Before mineralization, perforin and granzyme B—T cell‐needed therapeutic proteins for tumors—are preloaded with the MOF. Moreover, T cells are pretreated with processed tumor‐specific antigens to activate or produce memory before reprogramming the lysosomes, facilitating the T cell receptor (TCR) for release of the therapeutic proteins. Using T cells recombined by LYS‐NPs, a significant enhancement of breast cancer control is confirmed.

Sensory neurons promote profound suppressive effects on neutrophils during Streptococcus pyogenes infection and contribute to the pathogenesis of necrotizing infection (“flesh-eating disease”). Thus, the development of new antibacterial agents for necrotizing infection is promising because of the clear streptococcal neuro-immune communication. Herein, based on the immune escape membrane exterior and competitive membrane functions of the glioma cell membrane, a novel nano neuro-immune blocker capsule was designed to prevent neuronal activation and improve neutrophil immune responses for necrotizing infection. These nano neuro-immune blockers could neutralize streptolysin S, suppress neuron pain conduction and calcitonin gene-related peptide release, and recruit neutrophils to the infection site, providing a strong therapeutic effect against necrotizing infection. Furthermore, nano neuro-immune blockers could serve as an effective inflammatory regulator and antibacterial agent via photothermal effects under near-infrared irradiation. In the Streptococcus pyogenes-induced necrotizing fasciitis mouse model, nano neuro-immune blockers showed significant therapeutic efficacy by ameliorating sensitivity to pain and promoting the antibacterial effect of neutrophils.

No abstract

Immune response to implantation materials plays a critical role during early local inflammation and biomaterial-induced regeneration or restoration. A novel platelet concentrate termed i-PRF (injectable platelet-rich fibrin) has recently been developed without any additives by low centrifugation speeds. To date, scientists have investigated the capability of releasing growth factors to improve regeneration but have ignored whether i-PRF can inhibit the inflammatory effect around the wound. The present study investigated the anti-inflammation effects of i-PRF on immune response-related cells, especially macrophages and dendric cells. We found that i-PRF reduced pro-inflammatory M1 phenotype of macrophages and activated dendritic cells around muscle defect that was injected with bacterial suspension. Moreover, in vitro experiments showed similar results. i-PRF deleted inflammatory response caused by lipopolysaccharide to some extent. We determined that TLR4, an activator of inflammatory stimulation and p-p65, a key factor belongs to classical inflammatory related NF-κB signal pathway, can be inhibited by use of i-PRF. Results indicate the potential anti-inflammatory role of i-PRF during regeneration and restoration.