The treatment of long-gap (>10 mm) peripheral nerve injury (PNI) and spinal cord injury (SCI) remains a continuous challenge due to limited native tissue regeneration capabilities. The current clinical strategy of using autografts for PNI suffers from a source shortage, while the pharmacological treatment for SCI presents dissatisfactory results. Tissue engineering, as an alternative, is a promising approach for regenerating peripheral nerves and spinal cords. Through providing a beneficial environment, a scaffold is the primary element in tissue engineering. In particular, scaffolds with anisotropic structures resembling the native extracellular matrix (ECM) can effectively guide neural outgrowth and reconnection. In this review, the anatomy of peripheral nerves and spinal cords, as well as current clinical treatments for PNI and SCI, is first summarized. An overview of the critical components in peripheral nerve and spinal cord tissue engineering and the current status of regeneration approaches are also discussed. Recent advances in the fabrication of anisotropic surface patterns, aligned fibrous substrates, and 3D hydrogel scaffolds, as well as their
in vitro
and
in vivo
effects are highlighted. Finally, we summarize potential mechanisms underlying the anisotropic architectures in orienting axonal and glial cell growth, along with their challenges and prospects.
We investigated the association between cultural worldviews and climate change risk perceptions, support for climate friendly policies and climate change mitigation behaviours in a large Chinese sample. Items from Dake's cultural theory scales and Kahan's cultural cognition scale were presented to a Qualtrics online panel consisting of 515 Mandarin-speaking residents of Beijing. A series of factor analyses revealed that the combined item sets were best represented by four-dimensions: hierarchism, individualism, egalitarianism and fatalism. Mediation analysis revealed that respondents with egalitarian and non-fatalist worldviews perceived greater risk associated with climate change, which in turn predicted greater support for policies to manage climate change and increased mitigation behaviour. In addition, respondents who scored high on individualism were less likely to support climate change policies, but this effect was not mediated by risk perceptions. Overall, our results suggest cultural worldviews may influence policy support both directly and indirectly through risk perceptions.
Cartilage tissue engineering has arisen as a promising therapeutic option for degenerative joint diseases, such as osteoarthritis, in the hope of restoring the structure and physiological functions. Hydrogels are promising biomaterials for developing engineered constructs for cartilage regeneration. However, such cell-laden constructs could be exposed to elevated levels of reactive oxygen species (ROS) in the inflammatory microenvironment after being implanted into injured joints, which may affect their phenotype and normal functions and thereby hinder the regeneration efficacy. To attenuate ROS induced side effects, a multifunctional hydrogel with an innate anti-oxidative ability was produced in this study. The hydrogel was rapidly formed through a dynamic covalent bond between phenylboronic acid grafted hyaluronic acid (HA-PBA) and poly (vinyl alcohol) (PVA) and was further stabilized through a secondary crosslinking between the acrylate moiety on HA-PBA and the free thiol group from thiolated gelatin. The hydrogel is cyto-compatible and injectable and can be used as a bioink for 3D bioprinting. The viscoelastic properties of the hydrogels could be modulated through the hydrogel precursor concentration. The presence of dynamic covalent linkages contributed to its shear-thinning property and thus good printability of the hydrogel, resulting in the fabrication of a porous grid construct and a meniscus like scaffold at high structural fidelity. The bioprinted hydrogel promoted cell adhesion and chondrogenic differentiation of encapsulated rabbit adipose derived mesenchymal stem cells. Meanwhile, the hydrogel supported robust deposition of extracellular matrix components, including glycosaminoglycans and type II collagen, by embedded mouse chondrocytes in vitro. Most importantly, the hydrogel could protect encapsulated chondrocytes from ROS induced downregulation of cartilage-specific anabolic genes (ACAN and COL2) and upregulation of a catabolic gene (MMP13) after incubation with H2O2. Furthermore, intra-articular injection of the hydrogel in mice revealed adequate stability and good biocompatibility in vivo. These results demonstrate that this hydrogel can be used as a novel bioink for the generation of 3D bioprinted constructs with anti-ROS ability to potentially enhance cartilage tissue regeneration in a chronic inflammatory and elevated ROS microenvironment.
Recent progress in bioresorbable stents (BRSs) has provided a promising alternative for treating coronary artery disease. However, there is still lack of BRSs with satisfied compression and degradation performance for pediatric patients with congenital heart disease, leading to suboptimal therapy effects. Here, we developed a mechanically self-reinforced composite bioresorbable stent (cBRS) for congenital heart disease application. The cBRS consisted of poly(
p
-dioxanone) monofilaments and polycaprolactone/poly(
p
-dioxanone) core-shell composite yarns. Interlacing points in cBRS structure were partially bonded, offering the cBRS with significantly higher compression force compared to typical braids and remained good compliance. The suitable degradation profile of the cBRS can possibly preserve vascular remodeling and healing process. In addition, the controllable structural organization provides a method to customize the performance of the cBRS by altering the proportion of different components in the braids. The in vivo results suggested the cBRS supported the vessel wall similar to that of metallic stent. In both abdominal aorta and iliac artery of porcine, cBRS was entirely endothelialized within 1 month and maintained target vessels with good patency in the 12-month follow-up. The in vivo degradation profile of the cBRS is consistent with static degradation results in vitro. It is also demonstrated that there is minimal impact of pulsatile pressure of blood flow and variation of radial force on the degradation rate of the cBRS. Moreover, the lumen of cBRS implanted vessels were enlarged after 6 months, and significantly larger than the vessels implanted with metallic stent in 12 months.
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