The regeneration of diabetic bone defects remains challenging as the innate healing process is impaired by glucose fluctuation, reactive oxygen species (ROS), and overexpression of proteinases (such as matrix metalloproteinases, MMPs). A “diagnostic” and therapeutic dual‐logic‐based hydrogel for diabetic bone regeneration is therefore developed through the design of a double‐network hydrogel consisting of phenylboronic‐acid‐crosslinked poly(vinyl alcohol) and gelatin colloids. It exhibits a “diagnostic” logic to interpret pathological cues (glucose fluctuation, ROS, MMPs) and determines when to release drug in a diabetic microenvironment and a therapeutic logic to program different cargo release to match immune‐osteo cascade for better tissue regeneration. The hydrogel is also shown to be mechanically adaptable to the local complexity at the bone defect. Furthermore, the underlying therapeutic mechanism is elucidated, whereby the logic‐based cargo release enables the regulation of macrophage polarization by remodeling the mitochondria‐related antioxidative system, resulting in enhanced osteogenesis in diabetic bone defects. This study provides critical insight into the design and biological mechanism of dual‐logic‐based tissue‐engineering strategies for diabetic bone regeneration.

The regeneration of bone defects in patients with diabetes mellitus (DM) is remarkably impaired by hyperglycemia and over-expressed proinflammatory cytokines, proteinases (such as matrix metalloproteinases, MMPs), etc. In view of the fact that exosomes represent a promising nanomaterial, herein, we reported the excellent capacity of stem cells from apical papilla-derived exosomes (SCAP-Exo) to facilitate angiogenesis and osteogenesis whether in normal or diabetic conditions in vitro. Then, a bioresponsive polyethylene glycol (PEG)/DNA hybrid hydrogel was developed to support a controllable release of SCAP-Exo for diabetic bone defects. This system could be triggered by the elevated pathological cue (MMP-9) in response to the dynamic diabetic microenvironment. It was further confirmed that the administration of the injectable SCAP-Exo-loaded PEG/DNA hybrid hydrogel into the mandibular bone defect of diabetic rats demonstrated a great therapeutic effect on promoting vascularized bone regeneration. In addition, the miRNA sequencing suggested that the mechanism of dual-functional SCAP-Exo might be related to highly expressed miRNA-126-5p and miRNA-150-5p. Consequently, our study provides valuable insights into the design of promising bioresponsive exosome-delivery systems to improve bone regeneration in diabetic patients.

A meta-analysis was performed for a comparison of outcomes between sutureless technique and conventional surgery for primary repair for total anomalous pulmonary venous connection (TAPVC). Electronic databases including PubMed, EMbase, Scopus, and Cochrane Library were searched systematically for the single-arm studies regarding sutureless repair or conventional surgery, and two-arm studies compared the outcomes of sutureless repair and conventional surgery for TAPVC. Corresponding data were extracted and the methodological quality was assessed by two reviewers independently. 26 studies were included, involving a total of 2702 patients. It was observed that compared with conventional surgery, sutureless technique was associated with a lower occurrence rate of post-operative pulmonary veins obstruction (PVO) (4.6% vs. 13.5%, OR 0.54 in favor of sutureless technique) and re-operations due to PVO (3.4% vs. 12.4%, 0.25 in favor of sutureless technique). However, meta-analyses of post-operative early (OR 0.57; 95% CI 0.27-1.19; P = 0.13), late (OR 0.37; 95% CI 0.13-1.06; P = 0.13), and overall (OR 0.61; 95% CI 0.36-1.03; P = 0.07) mortality showed no significant difference between sutureless technique and conventional surgery. Compared with conventional surgery, sutureless technique was associated with a lower occurrence rate of post-operative PVO and re-operations due to PVO. Meanwhile, post-operative early, late, and overall mortality were not statistically different between two surgical approaches. Sutureless technique is beneficial in the primary repair of TAPVC regarding post-operative PVO and re-operations due to PVO. However, the level of evidence was low and randomized controlled trials should be designed to evaluate the safety and effectiveness of sutureless technique for TAPVC.

No abstract