Delivering living medicines with biomaterials
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Engineering bone/cartilage organoids: strategy, progress, and application
The concept and development of bone/cartilage organoids are rapidly gaining momentum, providing opportunities for both fundamental and translational research in bone biology. Bone/cartilage organoids, essentially miniature bone/cartilage tissues grown in vitro, enable the study of complex cellular interactions, biological processes, and disease pathology in a representative and controlled environment. This review provides a comprehensive and up-to-date overview of the field, focusing on the strategies for bone/cartilage organoid construction strategies, progresses in the research, and potential applications. We delve into the significance of selecting appropriate cells, matrix gels, cytokines/inducers, and construction techniques. Moreover, we explore the role of bone/cartilage organoids in advancing our understanding of bone/cartilage reconstruction, disease modeling, drug screening, disease prevention, and treatment strategies. While acknowledging the potential of these organoids, we discuss the inherent challenges and limitations in the field and propose potential solutions, including the use of bioprinting for organoid induction, AI for improved screening processes, and the exploration of assembloids for more complex, multicellular bone/cartilage organoids models. We believe that with continuous refinement and standardization, bone/cartilage organoids can profoundly impact patient-specific therapeutic interventions and lead the way in regenerative medicine.
Skeletal interoception and prospective application in biomaterials for bone regeneration
Accumulating research has shed light on the significance of skeletal interoception, in maintaining physiological and metabolic homeostasis related to bone health. This review provides a comprehensive analysis of how skeletal interoception influences bone homeostasis, delving into the complex interplay between the nervous system and skeletal system. One key focus of the review is the role of various factors such as prostaglandin E2 (PGE2) in skeletal health via skeletal interoception. It explores how nerves innervating the bone tissue communicate with the central nervous system to regulate bone remodeling, a process critical for maintaining bone strength and integrity. Additionally, the review highlights the advancements in biomaterials designed to utilize skeletal interoception for enhancing bone regeneration and treatment of bone disorders. These biomaterials, tailored to interact with the body’s interoceptive pathways, are positioned at the forefront of innovative treatments for conditions like osteoporosis and fractures. They represent a convergence of bioengineering, neuroscience, and orthopedics, aiming to create more efficient and targeted therapies for bone-related disorders. In conclusion, the review underscores the importance of skeletal interoception in physiological regulation and its potential in developing more effective therapies for bone regeneration. It emphasizes the need for further research to fully understand the mechanisms of skeletal interoception and to harness its therapeutic potential fully.
Insights from a century of data reveal global trends in ex situ living plant collections
Ex situ living plant collections play a crucial role in providing nature-based solutions to twenty-first century global challenges. However, the complex dynamics of these artificial ecosystems are poorly quantified and understood, affecting biodiversity storage, conservation and utilization. To evaluate the management of ex situ plant diversity, we analysed a century of data comprising 2.2 million records, from a meta-collection currently holding ~500,000 accessions and 41% of global ex situ species diversity. Our study provides critical insights into the historical evolution, current state and future trajectory of global living collections. We reveal sigmoidal growth of a meta-collection that has reached capacity in both total accessions and total diversity, and identify intrinsic constraints on biodiversity management, including a median survival probability of 15 years. We explore the impact of external constraints and quantify the influence of the Convention on Biological Diversity, which we link to reduced acquisition of wild-origin and internationally sourced material by 44% and 38%, respectively. We further define the impact of these constraints on ex situ conservation but highlight targeted initiatives that successfully mitigate these challenges. Ultimately, our study underscores the urgent need for strategic prioritization and the re-evaluation of ex situ biodiversity management to achieve both scientific and conservation goals.
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.
Dynamic effects of psychiatric vulnerability, loneliness and isolation on distress during the first year of the COVID-19 pandemic
The COVID-19 pandemic’s impact on mental health is challenging to quantify because pre-existing risk, disease burden and public policy varied across individuals, time and regions. Longitudinal, within-person analyses can determine whether pandemic-related changes in social isolation impacted mental health. We analyzed time-varying associations between psychiatric vulnerability, loneliness, psychological distress and social distancing in a US-based study during the first year of the pandemic. We surveyed 3,655 participants about psychological health and COVID-19-related circumstances every 2 weeks for 6 months. We combined self-reports with regional social distancing estimates and a classifier that predicted probability of psychiatric diagnosis at enrollment. Loneliness and psychiatric vulnerability both impacted psychological distress. Loneliness and distress were also linked to social isolation and stress associated with distancing, and psychiatric vulnerability shaped how regional distancing affected loneliness across time. Public health policies should address loneliness when encouraging social distancing, particularly in those at risk for psychiatric conditions.
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