Related Articles
3D imaging reveals changes in the neurovascular architecture of the murine calvarium with aging
Calvarial nerves, along with vasculature, influence skull formation during development and following injury, but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging. Studying the spatial distribution of nerves in the skull remains a challenge due to a lack of methods to quantify 3D structures in intact bone. To visualize calvarial 3D neurovascular architecture, we imaged nerves and endothelial cells with lightsheet microscopy. We employed machine-learning-based segmentation to facilitate high-resolution characterization from post-natal day 0 (P0) to 80 weeks. We found that TUBB3+ nerve density decreased with aging with the frontal bone demonstrating earlier onset age-related nerve loss than the parietal bone. In addition, nerves in the periosteum and dura mater exhibited similar yet distinct temporal patterns of nerve growth and loss. While no difference was observed in TUBB3+ nerves during skeletal maturation (P0 → 12 weeks), we did observe an increase in the volume of unmyelinated nerves in the dura mater. Regarding calvarial vasculature, larger CD31hiEmcn– vessel fraction increased with aging, while CD31hiEmcnhi vessel fraction was reduced. Throughout all ages, calvarial nerves maintained a preferential spatial association with CD31hiEmcnhi vessels, however, this association decreased with aging. Additionally, we used a model of Apert syndrome to explore the impact of suture-related disease on neurovascular architecture. Collectively, this 3D, spatiotemporal characterization of calvarial nerves throughout the lifespan and provides new insights into age-induced neurovascular architecture.
Evolution of temporomandibular joint reconstruction: from autologous tissue transplantation to alloplastic joint replacement
The reconstruction of the temporomandibular joint presents a multifaceted clinical challenge in the realm of head and neck surgery, underscored by its relatively infrequent occurrence and the lack of comprehensive clinical guidelines. This review aims to elucidate the available approaches for TMJ reconstruction, with a particular emphasis on recent groundbreaking advancements. The current spectrum of TMJ reconstruction integrates diverse surgical techniques, such as costochondral grafting, coronoid process grafting, revascularized fibula transfer, transport distraction osteogenesis, and alloplastic TMJ replacement. Despite the available options, a singular, universally accepted ‘gold standard’ for reconstructive techniques or materials remains elusive in this field. Our review comprehensively summarizes the current available methods of TMJ reconstruction, focusing on both autologous and alloplastic prostheses. It delves into the differences of each surgical technique and outlines the implications of recent technological advances, such as 3D printing, which hold the promise of enhancing surgical precision and patient outcomes. This evolutionary progress aims not only to improve the immediate results of reconstruction but also to ensure the long-term health and functionality of the TMJ, thereby improving the quality of life for patients with end-stage TMJ disorders.
Biomimetic 1,2-amino migration via photoredox catalysis
Synthetic organic chemists continually draw inspiration from biocatalytic processes to innovate synthetic methodologies beyond existing catalytic platforms. Within this context, although 1,2-amino migration represents a viable biochemical process, it remains underutilized within the synthetic organic chemistry community. Here we present a biomimetic 1,2-amino migration accomplished through the synergistic combination of biocatalytic mechanism and photoredox catalysis. This platform enables the modular synthesis of γ-substituted β-amino acids by utilizing abundant α-amino-acid derivatives and readily available organic molecules as coupling partners. This mild method features excellent substrate and functionality compatibility, affording a diverse range of γ-substituted β-amino acids (more than 80 examples) without the need for laborious multistep synthesis. Mechanistic studies, supported by both experimental observations and theoretical analysis, indicate that the 1,2-amino migration mechanism involves radical addition to α-vinyl-aldimine ester, 3-exo–trig cyclization and a subsequent rearrangement process. We anticipate that this transformation will serve as a versatile platform for the highly efficient construction of unnatural γ-substituted β-amino acids.
Effect of regional crosstalk between sympathetic nerves and sensory nerves on temporomandibular joint osteoarthritic pain
Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Personalized bioceramic grafts for craniomaxillofacial bone regeneration
The reconstruction of craniomaxillofacial bone defects remains clinically challenging. To date, autogenous grafts are considered the gold standard but present critical drawbacks. These shortcomings have driven recent research on craniomaxillofacial bone reconstruction to focus on synthetic grafts with distinct materials and fabrication techniques. Among the various fabrication methods, additive manufacturing (AM) has shown significant clinical potential. AM technologies build three-dimensional (3D) objects with personalized geometry customizable from a computer-aided design. These layer-by-layer 3D biomaterial structures can support bone formation by guiding cell migration/proliferation, osteogenesis, and angiogenesis. Additionally, these structures can be engineered to degrade concomitantly with the new bone tissue formation, making them ideal as synthetic grafts. This review delves into the key advances of bioceramic grafts/scaffolds obtained by 3D printing for personalized craniomaxillofacial bone reconstruction. In this regard, clinically relevant topics such as ceramic-based biomaterials, graft/scaffold characteristics (macro/micro-features), material extrusion-based 3D printing, and the step-by-step workflow to engineer personalized bioceramic grafts are discussed. Importantly, in vitro models are highlighted in conjunction with a thorough examination of the signaling pathways reported when investigating these bioceramics and their effect on cellular response/behavior. Lastly, we summarize the clinical potential and translation opportunities of personalized bioceramics for craniomaxillofacial bone regeneration.
Responses