Pharmacological manipulation of macrophage autophagy effectively rejuvenates the regenerative potential of biodegrading vascular graft in aging body.

Declined regenerative potential and aggravated inflammation upon aging create an inappropriate environment for arterial regeneration. Macrophages are one of vital effector cells in the immune microenvironment, especially during biomaterials mediated repairing process. Here, we revealed that the macrophage autophagy decreased with aging, which led to aggravated inflammation, thereby causing poor vascular remodeling of artificial grafts in aging body. Through loading the autophagy-targeted drugs, rapamycin and 3-MA (3-methyladenine), in PCL (polycaprolactone) sheath of the PGS (poly glycerol sebacate) - PCL vascular graft, the essential role of macrophage autophagy was confirmed in regulating macrophage polarization and biomaterial degradation. Moreover, the utilization of rapamycin promoted anti-inflammatory polarization of macrophage by activating autophagy, which further promoted myogenic differentiation of vascular progenitor cells and accelerated endothelialization. Our study elucidated the contribution of pharmacological manipulation of macrophage autophagy in promoting regeneration of small caliber artery, which may pave a new avenue for clinical translation of vascular grafts in aging body.

Mussel patterned with 4D biodegrading elastomer durably recruits regenerative macrophages to promote regeneration of craniofacial bone.

Crosstalk between bone marrow mesenchymal stem cells (BMSCs) and macrophages plays vital role in bone healing. By investigating the mechanism of collagen membrane-guided bone regeneration, we found compact structure and rapid membrane degradation compromised the duration of M2 macrophages influx, which restricts the recruitment of BMSCs that is essential for bone healing. To tackle this issue, a biodegrading elastomeric compound consisting of poly(glycerol sebacate) (PGS) and polycaprolactone (PCL) was fabricated into hierarchically porous membrane. The rational design of 3D microstructure enabled sufficient polydopamine (PDA) coating. Without any addition of growth factors, the 3D-patterned PDA membrane enables early and durable influx of M2 macrophages, which in turn promotes BMSCs recruitment and osteogenic differentiation. Furthermore, 4D-morphing of the membrane fully regenerates the dome shaped calvarial bone as well as arc-shape bone in peri-implant alveolar defect without filling xenogenous substitute. This study revealed the superiority of 3D printed microstructures in immunomodulatory materials. The availability of 4D-morphing for PGS/PCL construct expanded their advantages in reconstructing craniofacial bone.

Fast degrading elastomer stented fascia remodels into tough and vascularized construct for tracheal regeneration.

Tracheal reconstruction remains a major surgical challenge, mainly owing to the scarce of resilient hollow grafts with identifiable vascular pedicle in humans. In this study, we developed a three-layer, elastomeric, trachea-like composite made of poly glycerol sebacate (PGS) and polycaprolactone (PCL), which presented appropriate resilient property, timely degradation and interconnected pores. C shape PCL rings fabricated with selective laser sintering (SLS) techniques are regularly positioned around porous PGS tubes and fixed by PCL electrospinning sheath. Such an elastomeric composite underwent host remodeling including rapid vascularization and tissue infiltration after fascia wrapping. With degrading of PGS, C rings well incorporated into growing fascia and lead to the formation of pedicled tracheal grafts, which attributes to the strong and resilient properties of generated hollow grafts thus enabled orthotopic transplantation in segmental tracheal defect. Progressive remodeling on such vascularized and mechanically stable grafts resulted in epithelium regeneration on luminal side as well as production of adequate amount of collagen and elastin, which warrantees the air passage during breathing. Future study employing large animal models more representative of human tracheal regeneration is warranted before clinical translation. Using fast degrading PGS combined with PCL rings represents a philosophical shift from the prevailing focus on tough grafts in airway reconstruction and may impact regenerative medicine in general.

Prevention and Treatment of Lower Limb Deep Vein Thrombosis after Radiofrequency Catheter Ablation: Results of a Prospective active controlled Study.

We conducted a prospective, single-center, active controlled study from July 2013 to January 2015, in Chinese patients with rapid ventricular arrhythmia who had received radiofrequency catheter ablation (RFCA) treatment to determine formation of lower extremity deep vein thrombosis (LDVT) post RFCA procedure, and evaluated the effect of rivaroxaban on LDVT. Patients with asymptomatic pulmonary thromboembolism who had not received any other anticoagulant and had received no more than 36 hours of treatment with unfractionated heparin were included. Post RFCA procedure, patients received either rivaroxaban (10 mg/d for 14 days beginning 2-3 hours post-operation; n = 86) or aspirin (100 mg/d for 3 months beginning 2-3 hours post-operation; n = 90). The primary outcome was a composite of LDVT occurrence, change in diameter of femoral veins, and safety outcomes that were analyzed based on major or minor bleeding events. In addition, blood flow velocity was determined. No complete occlusive thrombus or bleeding events were reported with either of the group. The lower incidence rate of non-occluded thrombus in rivaroxaban (5.8%) compared to the aspirin group (16.7%) indicates rivaroxaban may be administered post-RFCA to prevent and treat femoral venous thrombosis in a secure and effective way with a faster inset of action than standard aspirin therapy.