No abstract

A guided bone regeneration membrane is a pivotal therapeutic modality used to maintain sufficient space for bone regeneration, which is of great significance in curing alveolar bone defects. Metformin has been found to possess the ability of promoting osteogenic differentiation of bone mesenchymal stem cells. To develop guided bone regeneration membranes with better osteoinductive ability, metformin was incorporated into polycaprolactone/chitosan nanofibrous membranes by electrospinning technique, followed by glutaraldehyde crosslinking to reinforce chitosan stability in aqueous solutions. The fabricated nanofibrous membranes were then characterized by scanning electron microscope, Fourier transform infrared spectroscopy, water contact angle testing, mechanical properties test, and drug release test. Furthermore, rats bone mesenchymal stem cells were seeded on membranes for the evaluation of the effect of metformin-loaded polycaprolactone/chitosan nanofibrous membranes on cell morphology, alkaline phosphate activity, and osteogenic mineralization in vitro. Our results showed that nanofibers were fabricated successfully with smooth surface free from beads formation. The crosslinked-polycaprolactone/chitosan/metformin membranes had a more appropriate water contact angle of 44.25 ± 1.37° and the drug release curve of metformin featured early sudden release and slow release in the later stage over a 23-day period. Besides, in vitro studies suggested that the crosslinked-polycaprolactone/chitosan/metformin membrane was more suitable for cell adhesion, proliferation, and osteogenic differentiation of bone mesenchymal stem cells. Consequently, the metformin-loaded polycaprolactone/chitosan nanofibrous membranes would be promoted for bone regeneration as guided bone regeneration membranes.

Full-thickness oral mucosal defects are accompanied by significant blood loss and frequent infections. Instead of conventional therapies that separate hemostasis and anti-inflammation in steps, emerging hydrogels can integrate multiple functions for the successive process after defect including hemostasis/inflammatory phase, proliferative phase, and remodeling phase. However, these functions can be easily compromised by rapid swelling and degradation of hydrogels in wet oral environment. Herein, a low-swelling adhesive hydrogel with rapid hemostasis and potent anti-inflammatory capability was developed using a dual cross-linking strategy as well as a safe and facile fabrication method. It was double cross-linked hydrogel consisting of gelatin methacrylate (GelMA), nanoclay, and tannic acid (TA) (referred to as GNT). GNT hydrogel exhibited low-swelling (one-eighth of that of GelMA), excellent stretchability (211.86%), and good adhesive properties (5 times the adhesive strength of GelMA). Physicochemical characterization illuminated the close interactions among the three components. A systematic investigation of the therapeutic effects of GNT hydrogels was performed. In vitro and in vivo experimental results demonstrated the potent hemostatic property and excellent antibacterial and anti-inflammatory effects of GNT hydrogels. The RNA sequencing analysis results for rat full-thickness oral mucosal samples showed that GNT reduced inflammation levels by down-regulating the expression of multiple inflammation-related pathways, including TNF and IL-17 pathways. It also enhanced the expression levels of tissue regeneration-related genes and thus accelerated defective mucosal repair. More importantly, the therapeutic effects of GNT were superior to those of a commercial oral tissue repair membrane when applied for full-thickness oral mucosal defect repair in rabbits. In summary, the prepared low-swelling adhesive GNT hydrogel with rapid hemostasis and potent anti-inflammatory is a promising therapy for full-thickness mucosal defect in the moist and dynamic oral environment.

It has been confirmed that substantial vascularization is an effective strategy to heal large-scale bone defects in the field of bone tissue engineering. The local application of deferoxamine (DFO) is among the most common and effective methods for promoting the formation of blood vessels, although its short half-life in plasma, rapid clearance, and poor biocompatibility limit its therapeutic suitability. Herein, zeolitic imidazolate framework-8 (ZIF-8) was selected as a vehicle to extend the halflife of DFO. In the present study, a nano DFO-loaded ZIF-8 (DFO@ZIF-8) drug delivery system was established to promote angiogenesis−osteogenesis coupling. The nanoparticles were characterized, and their drug loading efficiency was examined to confirm the successful synthesis of nano DFO

bullet points:1. The review discusses the current strategies of 3D bioprinting applied in fabrication of vasculature constructs including vascularized tissue constructs and vascular tubular structures.2. Vascularized tissue constructs are generated by direct printing or indirect printing and extrusion bioprinting is the main technique in these two printing strategies.3. Free-standing vascular structures can be fabricated by a variety of strategies to adjust the diameter and branches of vascular-like structures.