Bone self-healing is limited and generally requires external intervention to augment bone repair and regeneration. While traditional methods for repairing bone defects such as autografts, allografts, and xenografts have been widely used, they all have corresponding disadvantages, thus limiting their clinical use. Despite the development of a variety of biomaterials, including metal implants, calcium phosphate cements (CPC), hydroxyapatite, etc., the desired therapeutic effect is not fully achieved. Currently, polymeric scaffolds, particularly hydrogels, are of interest and their unique configurations and tunable physicochemical properties have been extensively studied. This review will focus on the applications of various cutting-edge bioactive hydrogels systems in bone regeneration, as well as their advantages and limitations. We will examine the composition and defects of the bone, discuss the current biomaterials for bone regeneration, and classify recently developed polymeric materials for hydrogel synthesis. We will also elaborate on the properties of desirable hydrogels as well as the fabrication techniques and different delivery strategies. Finally, the existing challenges, considerations, and the future prospective of hydrogels in bone regeneration will be outlined.
A Gd(III)-nanodiamond conjugate [Gd(III)-ND] was prepared and characterized, enabling detection of nanodiamonds by MR imaging. The Gd(III)-ND particles significantly reduced the T1 of water protons with a per-Gd(III) relaxivity of 58.82 ± 1.18 mM−1s−1 at 1.5 Tesla (60 MHz). This represents a tenfold increase compared to the monomer Gd(III) complex (r1 = 5.42 ± 0.20 mM−1s−1) and is among the highest per-Gd(III) relaxivities reported.
Cisplatin and other DNA-damaging chemotherapeutics are widely used to treat a broad spectrum of malignancies. However, their application is limited by both intrinsic and acquired chemoresistance. Most mutations that result from DNA damage are the consequence of error-prone translesion DNA synthesis, which could be responsible for the acquired resistance against DNAdamaging agents. Recent studies have shown that the suppression of crucial gene products (e.g., REV1, REV3L) involved in the errorprone translesion DNA synthesis pathway can sensitize intrinsically resistant tumors to chemotherapy and reduce the frequency of acquired drug resistance of relapsed tumors. In this context, combining conventional DNA-damaging chemotherapy with siRNAbased therapeutics represents a promising strategy for treating patients with malignancies. To this end, we developed a versatile nanoparticle (NP) platform to deliver a cisplatin prodrug and REV1/ REV3L-specific siRNAs simultaneously to the same tumor cells. NPs are formulated through self-assembly of a biodegradable poly(lactide-coglycolide)-b-poly(ethylene glycol) diblock copolymer and a self-synthesized cationic lipid. We demonstrated the potency of the siRNA-containing NPs to knock down target genes efficiently both in vitro and in vivo. The therapeutic efficacy of NPs containing both cisplatin prodrug and REV1/REV3L-specific siRNAs was further investigated in vitro and in vivo. Quantitative realtime PCR results showed that the NPs exhibited a significant and sustained suppression of both genes in tumors for up to 3 d after a single dose. Administering these NPs revealed a synergistic effect on tumor inhibition in a human Lymph Node Carcinoma of the Prostate xenograft mouse model that was strikingly more effective than platinum monotherapy.siRNA delivery | chemosensitivity | combination therapy A dvances in genomics and cell biology have highlighted the heterogeneity and complexity of cancer. It is generally accepted that cancer is usually the result of a combination of interconnected disease pathways that may not be treated effectively with 1D therapeutic mechanisms (1). The inhibition of a pathway by a single-drug therapy often results in the emergence of drug resistance and tumor relapse, largely because of pathway redundancy, cross-talk, compensatory and neutralizing actions, and antitarget activities that commonly occur with single-drug cancer therapy (2). In some cases, relapse can result in the emergence of phenotypically distinct and possibly more virulent tumors. For example, treatment of prostatic adenocarcinoma with androgen ablation therapies, such as abiraterone or enzalutamide, results in the development of abiraterone or enzalutamide refractory castration-resistant prostate cancer that is phenotypically nonadenocarcinoma and represents a rare and often lethal form of prostate cancer with a neuroendocrine phenotype (3).Platinum agents are among the most widely used cytotoxic agents for cancer therapy. Cisplatin and other DNA adductforming chemotherapeutics caus...
Conjugate agent: A GdIII enriched DNA‐AuNP conjugate for intracellular magnetic resonance and fluorescence imaging is reported. The agent exhibits high relaxivity per particle and high cell uptake properties that provide a means to image and map small cell populations.
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