The rapid emergence of antibiotic resistance in pathogenic microbes is becoming an imminent global public health problem. Local application of antibiotics might be a solution. In local application, materials need to act as the drug delivery system. The drug delivery system should be biodegradable and prolonged antibacterial effect should be provided to satisfy clinical demand. Hydrogel is a promising material for local antibacterial application. Hydrogel refers to a kind of biomaterial synthesized by a water-soluble natural polymer or a synthesized polymer, which turns into gel according to the change in different signals such as temperature, ionic strength, pH, ultraviolet exposure etc. Because of its high hydrophilicity, unique three-dimensional network, fine biocompatibility and cell adhesion, hydrogel is one of the suitable biomaterials for drug delivery in antimicrobial areas. In this review, studies from the past 5 years were reviewed, and several types of antimicrobial hydrogels according to different ingredients, different preparations, different antimicrobial mechanisms, different antimicrobial agents they contained and different applications, were summarized. The hydrogels loaded with metal nanoparticles as a potential method to solve antibiotic resistance were highlighted. Finally, future prospects of development and application of antimicrobial hydrogels are suggested.

In recent years, in situ chemotherapy mediated by biodegradable polymer platforms has attracted increased attention. Herein, an advanced drug delivery system, combretastatin A-4 (CA4) and docetaxel (DTX)-loaded microsphere embedded in injectable thermosensitive polypeptide hydrogel (i.e., hydrogel-microsphere (Gel-MP) construct), was reported for sequential release of drugs with different mechanisms to treat osteosarcoma synergistically. The Gel-MP construct showed sequential biodegradability and excellent biocompatibility. CA4 was preferentially released from hydrogel with faster degradation to disturb the vascular structure of the tumor and reduce the exchange of nutrients between the tumor and surrounding tissues, which created interstitial space in the tissue for DTX penetration to inhibit tumor cell proliferation. The in vivo treatment with Gel/CA4-MP/DTX efficiently suppressed the growth of mouse K7 osteosarcoma compared to other formulations. More importantly, by systematical study of histopathology and immunohistochemistry, the Gel-MP construct can significantly upregulate antiproliferation effect and reduce toxicity of drugs. Therefore, this injectable and locally sequential delivery system has a bright prospect in clinical application of in situ synergistic chemotherapy.

Titanium alloy prostheses have been widely used for the treatment of orthopedic diseases, in which the interconnected porosity and appropriate pore size are crucial for the osseointegration capacity. Three-dimensional (3D) printing technology provides an efficient method to construct prosthesis scaffolds with controllable internal and surface structure, but printing high-porosity (>60%) scaffolds with pore diameters below 300 μm as implants structures has not yet been studied. In this work, four types of titanium alloy scaffolds with interconnected porosity more than 70% were successfully prepared by selective laser melting (SLM). The actual mean pore sizes of cylindrical scaffolds are 542, 366, 202, and 134 μm. Through the in vitro characterization of the scaffolds, in vivo experiments, and mechanical experiments, it is concluded that as the scaffold pore diameter decreases, the titanium alloy scaffold with diameter of 202 μm has the strongest osseointegration ability and is also the most stable one with the surrounding bone. These findings provide a reference for the clinical pore-size design of porous scaffolds with optimal bone growth stability on the surface of the titanium alloy implant.

TMEM16A, a calcium-activated chloride channel (CaCC), is highly amplified and expressed in human cancers and is involved in the growth and metastasis of some malignancies. Inhibition of TMEM16A represents a novel pharmaceutical approach for the treatment of cancers and metastases. The purpose of this study is to identify a new TMEM16A inhibitor, investigate the effects of this inhibitor on the proliferation and metastasis of TMEM16A-amplified SW620 cells, and to elucidate the underlying molecular mechanism in vitro. We identified a novel small-molecule TMEM16A inhibitor dehydroandrographolide (DP). By using patch clamp electrophysiology, we showed that DP inhibited TMEM16A chloride currents in Fisher rat thyroid (FRT) cells that were transfected stably with human TMEM16A and in TMEM16A-overexpressed SW620 cells but did not alter cystic fibrosis transmembrane conductance regulator (CFTR) chloride currents. Further functional studies showed that DP suppressed the proliferation of SW620 cells in a dose- and time-dependent manner using MTT assays. Moreover, DP significantly inhibited migration and invasion of SW620 cells as detected by wound-healing and transwell assays. Further mechanistic study demonstrated that knockdown of human TMEM16A decreased the inhibitory effect of DP on the proliferation of SW620 cells and that TMEM16A-dependent cells (SW620 and HCT116) were more sensitive to DP than TMEM16A-independent cells (SW480 and HCT8). In addition, we found that treatment of SW620 cells with DP led to a decrease in TMEM16A protein levels but had no effect on TMEM16A mRNA levels. The current work reveals that DP, a novel TMEM16A inhibitor, exerts its anticancer activity on SW620 cells partly through a TMEM16A-dependent mechanism, which may introduce a new targeting approach for an antitumour therapy in TMEM16A-amplified cancers.