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Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis

Bone Research 2019年第4期7卷 354-370页

作者： Courtney MMazur Jonathon JWoo Cristal SYee Aaron JFields Claire Acevedo Karsyn NBailey Serra Kaya Tristan WFowler Jeffrey CLotz Alexis Dang Alfred CKuo Thomas PVail Tamara Alliston Department of Orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143USA UC Berkeley-UCSF Graduate Program in Bioengineering San FranciscoCA 94143USA Department of Mechanical Engineering University of UtahSalt Lake CityUT 84112USA San Francisco Veterans Affairs Medical Center San FranciscoCA 94121USA

Osteoarthritis(OA),long considered a primary disorder of articular cartilage,is commonly associated with subchondral bone ***,the cellular mechanisms responsible for changes to subchondral bone in OA,and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration,remain *** knee joints from human patients with end-stage OA,we found evidence of profound defects in osteocyte *** of osteocyte perilacunar/canalicular remodeling(PLR)was most severe in the medial compartment of OA subchondral bone,with lower protease expression,diminished canalicular networks,and disorganized and hypermineralized extracellular *** a step toward evaluating the causality of PLR suppression in OA,we ablated the PLR enzyme MMP13 in osteocytes while leaving chondrocytic MMP13 intact,using Cre recombinase driven by the 9.6-kb DMP1 *** only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone,but it also compromised *** in the absence of injury,osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content,change chondrocyte production of collagen II,aggrecan,and MMP13,and increase the incidence of cartilage lesions,consistent with early ***,in humans and mice,defects in PLR coincide with cartilage ***-derived MMP13 emerges as a critical regulator of cartilage homeostasis,likely via its effects on ***,these findings implicate osteocytes in bone-cartilage crosstalk in the joint and suggest a causal role for suppressed perilacunar/canalicular remodeling in osteoarthritis.

关键词： MMP13 homeostasis likely

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Bottom-up Biomaterial strategies for creating tailored stem cells in regenerative medicine

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Frontiers in bioengineering and biotechnology 2025年 13卷 1581292页

作者： Brenda Cruz-Gonzalez Ellie Johandes Dominique Gramm Donny Hanjaya-Putra Department of Aerospace and Mechanical Engineering Bioengineering Graduate Program University of Notre Dame Notre Dame IN United States. Harper Cancer Research Institute University of Notre Dame Notre Dame IN United States. Department of Chemical and Biomolecular Engineering University of Notre Dame Notre Dame IN United States. Center for Stem Cells and Regenerative Medicine University of Notre Dame Notre Dame IN United States.

Biomaterial-assisted stem cell therapies hold immense promise for regenerative medicine, yet clinical translation remains challenging. This review focuses on recent advances and persistent limitations in applying induced pluripotent stem cells (iPSCs), endothelial colony-forming cells (ECFCs), multipotent mesenchymal stromal cells (MSCs), and embryonic stem cells (ESCs) within engineered microenvironments. We introduce a novel "bottom-up" approach to biomaterial design. This approach focuses first on understanding the fundamental biological properties and microenvironmental needs of stem cells, then engineering cell-instructive biomaterials to support them. Unlike conventional methods that adapt cells to pre-existing materials, this strategy prioritizes designing biomaterials from the molecular level upward to address key challenges, including differentiation variability, incomplete matching of iPSCs to somatic counterparts, functional maturity of derived cells, and survival of ECFCs/MSCs in therapeutic niches. By replicating lineage-specific mechanical, chemical, and spatial cues, these tailored biomaterials enhance differentiation fidelity, reprogramming efficiency, and functional integration. This paradigm shift from passive scaffolds to dynamic, cell-instructive platforms bridges critical gaps between laboratory success and clinical translation, offering a transformative roadmap for regenerative medicine and tissue engineering.

关键词： 3D printing backpack molecules biomaterials disease modeling drug screening nanoparticles stem cells tissue engineerings

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Tribological properties of hydroxyapatite-coated nanorods on Ti-6Al-4V surfaces

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Scientific reports 2025年第1期15卷 19113页

作者： Sarah Akua Osafo Tabiri Asumadu Desmond Klenam Precious Etinosa John David Obayemi Benjamin Agyei-Tuffour Abu Yaya David Dodoo-Arhin Stanley Chijioke Eluu Wole Soboyejo Department of Materials Science and Engineering School of Engineering Sciences College of Basic and Applied Sciences University of Ghana Legon Accra Ghana. Department of Biomaterial Sciences Dental School University of Ghana Korle Bu Campus Accra Ghana. Department of Mechanical Engineering Program in Materials Science and Engineering Worcester Polytechnic Institute 100 Institute Road Worcester MA 01609 USA. Department of Materials Engineering Sunyani Technical University Sunyani Ghana. Global Center of Advanced Materials and Manufacturing Department of Mechanical Engineering College of Engineering State University of New York (SUNY) Polytechnic Institute 100 Seymour Street Utica NY 13502 USA. Next Frontiers in Advanced Material Laboratory School of Chemical and Metallurgical Engineering University of the Witwatersrand 1 Jan Smuts Avenue Johannesburg 2050 South Africa. Department of Biomedical Engineering Worcester Polytechnic Institute Gateway Park Life Sciences and Bioengineering Centre 60 Prescott Street Worcester MA 01609 USA. Department of Biotechnology Ebonyi State University Abakaliki Nigeria. Department of Pharmaceutical Microbiology and Biotechnology Faculty of Pharmaceutical Sciences Nnamdi Azikiwe University Awka Anambra State Nigeria. Department of Mechanical Engineering Program in Materials Science and Engineering Worcester Polytechnic Institute 100 Institute Road Worcester MA 01609 USA. soboyew@sunypoly.edu. Global Center of Advanced Materials and Manufacturing Department of Mechanical Engineering College of Engineering State University of New York (SUNY) Polytechnic Institute 100 Seymour Street Utica NY 13502 USA. soboyew@sunypoly.edu. Department of Biomedical Engineering Worcester Polytechnic Institute Gateway Park Life Sciences and Bioengineering Centre 60 Prescott Street Worcester MA 01609 USA. soboyew@sunypoly.edu.

This paper presents the tribological properties and bioactivity of nanostructured hydroxyapatite (HA) from biowaste sources and coated onto Ti-6Al-4V substrates using a novel pack cementation method. The process introduced HA pillars/nanorods on the surfaces of Ti-6Al-4V to enhance their osseointegration for dental implants. The mechanical and tribological properties were studied with nanoindentation, and pin-on-disk techniques, following the microstructural characterization of the coatings with atomic force microscopy, X-ray diffraction, Raman spectroscopy, scanning electron microscopy, and energy dispersive x-ray spectroscopy. The study also examines the surface bioactivity and elucidates the underlying friction and wear mechanisms of the HA-coated and annealed Ti-6Al-4V surface. The study results show a bone bonding capacity of the biowaste-derived HA-coated substrate with improved hardness and tribological properties. The implications of the study are discussed for the development of nano-structured HA-coated Ti-6Al-4V for dental implants with improved osseointegration for dental and biomedical applications.

关键词： Bioactivity Dental implants Osseointegration Surface modification Titanium alloys Wear resistance

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Changing the public perception of human embryology ( vol 25, pg 1717, 2023)

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NATURE CELL BIOLOGY 2023年第12期25卷 1884-1884页

作者： Rivron, Nicolas C. Martinez-Arias, Alfonso Sermon, Karen Mummery, Christine Scholer, Hans R. Wells, James Nichols, Jenny Hadjantonakis, Anna-Katerina Lancaster, Madeline A. Moris, Naomi Fu, Jianping Sturmey, Roger G. Niakan, Kathy Rossant, Janet Kato, Kazuto Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) Vienna BioCenter (VBC) Vienna Austria Systems Bioengineering MELIS Universidad Pompeu Fabra and Catalan Institution for Research and Advanced Studies (ICREA) Barcelona Spain Research Group Reproduction and Genetics Vrije Universiteit Brussel Brussels Belgium European Society for Human Reproduction and Embryology (ESHRE) Strombeek-Bever Belgium Leiden University Medical Center Leiden the Netherlands Max Planck Institute for Molecular Biomedicine Münster Germany Center for Stem Cell and Organoid Medicine Cincinnati Children’s Hospital Medical Center Cincinnati OH USA Division of Developmental Biology Cincinnati Children’s Hospital Medical Center Cincinnati OH USA MRC Human Genetics Unit Institute of Genetics and Cancer The University of Edinburgh Crewe Road Edinburgh UK Developmental Biology Program Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York NY USA MRC Laboratory of Molecular Biology Cambridge UK The Francis Crick Institute London UK Department of Mechanical Engineering University of Michigan Ann Arbor MI USA Department of Biomedical Engineering University of Michigan Ann Arbor MI USA Department of Cell & Developmental Biology University of Michigan Medical School Ann Arbor MI USA Biomedical Institute for Multimorbidity Hull York Medical School University of Hull Hull UK Cambridge Reproduction University of Cambridge Cambridge UK The Centre for Trophoblast Research Department of Physiology Development and Neuroscience University of Cambridge Cambridge UK Human Embryo and Stem Cell Laboratory The Francis Crick Institute London UK Wellcome Trust–Medical Research Council Stem Cell Institute University of Cambridge Jeffrey Cheah Biomedical Centre Cambridge UK Epigenetics Programme Babraham Institute Cambridge UK The Hospital for Sick Children Toronto ON Canada Department of Biomedical Ethics and Public Policy Graduate School of Medicin

Human embryology is flourishing thanks to an impetus provided by embryo models formed from stem cells. These scientific advances require meticulous experimental work and a refined ethical framework, but also sensible ... 详细信息

关键词： Embryology Embryonic stem cells

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Advancements in Wearable and Implantable BioMEMS Devices: Transforming Healthcare Through Technology

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Micromachines 2025年第5期16卷 522页

作者： Vishnuram Abhinav Prithvi Basu Shikha Supriya Verma Jyoti Verma Atanu Das Savita Kumari Prateek Ranjan Yadav Vibhor Kumar Department of Electrical Engineering Indian Institute of Technology Bombay Mumbai 400076 Maharashtra India. Department of Electrical Engineering Texas A&M University College Station TX 77843 USA. Integrated Disease Surveillance Program National Health Mission Guwahati 781005 Assam India. Department of Electronics and Communication Engineering Manipal Institute of Technology Manipal Academy of Higher Education Manipal 576104 Karnataka India. Department of Biosciences and Bioengineering Indian Institute of Technology Bombay Mumbai 400076 Maharashtra India. School of Mechanical and Materials Engineering University College Dublin D04 V1W8 Dublin Ireland.

Wearable and implantable BioMEMSs (biomedical microelectromechanical systems) have transformed modern healthcare by enabling continuous, personalized, and minimally invasive monitoring, diagnostics, and therapy. Wearable BioMEMSs have advanced rapidly, encompassing a diverse range of biosensors, bioelectronic systems, drug delivery platforms, and motion tracking technologies. These devices enable non-invasive, real-time monitoring of biochemical, electrophysiological, and biomechanical signals, offering personalized and proactive healthcare solutions. In parallel, implantable BioMEMS have significantly enhanced long-term diagnostics, targeted drug delivery, and neurostimulation. From continuous glucose and intraocular pressure monitoring to programmable drug delivery and bioelectric implants for neuromodulation, these devices are improving precision treatment by continuous monitoring and localized therapy. This review explores the materials and technologies driving advancements in wearable and implantable BioMEMSs, focusing on their impact on chronic disease management, cardiology, respiratory care, and glaucoma treatment. We also highlight their integration with artificial intelligence (AI) and the Internet of Things (IoT), paving the way for smarter, data-driven healthcare solutions. Despite their potential, BioMEMSs face challenges such as regulatory complexities, global standardization, and societal determinants. Looking ahead, we explore emerging directions like multifunctional systems, biodegradable power sources, and next-generation point-of-care diagnostics. Collectively, these advancements position BioMEMS as pivotal enablers of future patient-centric healthcare systems.

关键词： bioMEMS biocompatible materials cardiac monitoring chronic disease management drug delivery healthcare monitoring implantable devices point of care societal determinants wearable medical devices

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Go with the FLOW: Visualizing spatiotemporal dynamics in optical widefield calcium imaging

arXiv

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arXiv 2020年

作者： Linden, Nathaniel J. Tabuena, Dennis R. Steinmetz, Nicholas A. Moody, William J. Brunton, Steven L. Brunton, Bingni W. Department of Bioengineering University of Washington Seattle United States Department of Biology University of Washington Seattle United States Graduate Program in Neuroscience University of Washington Seattle United States Department of Biological Structure University of Washington Seattle United States Department of Mechanical Engineering University of Washington Seattle United States

Widefield calcium imaging has recently emerged as a powerful experimental technique to record coordinated large-scale brain activity. These measurements present a unique opportunity to characterize spatiotemporally coherent structures that underlie neural activity across many regions of the brain. In this work, we leverage analytic techniques from fluid dynamics to develop a visualization framework that highlights features of flow across the cortex, mapping wave fronts that may be correlated with behavioral events. First, we transform the time series of widefield calcium images into time-varying vector fields using optic flow. Next, we extract concise diagrams summarizing the dynamics, which we refer to as FLOW (flow lines in optical widefield imaging) portraits. These FLOW portraits provide an intuitive map of dynamic calcium activity, including regions of initiation and termination, as well as the direction and extent of activity spread. To extract these structures, we use the finite-time Lyapunov exponent (FTLE) technique developed to analyze time-varying manifolds in unsteady fluids. Importantly, our approach captures coherent structures that are poorly represented by traditional modal decomposition techniques. We demonstrate the application of FLOW portraits on three simple synthetic datasets and two widefield calcium imaging datasets, including cortical waves in the developing mouse and spontaneous cortical activity in an adult mouse. © 2020, CC BY.

关键词： Brain

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Rationally designed chimeric solid-binding peptides for tailoring solid interfaces

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Medical Devices and Sensors 2020年第3期3卷

作者： Yucesoy, Deniz T. Khatayevich, Dimitry Tamerler, Candan Sarikaya, Mehmet GEMSEC Genetically Engineered Materials Science and Engineering Center University of Washington SeattleWA United States Department of Materials Science and Engineering University of Washington SeattleWA United States Department of Mechanical Engineering Bioengineering Program Institute for Bioengineering Research University of Kansas Lawrence LawrenceKS United States Department of Chemical Engineering University of Washington SeattleWA United States Department of Oral Health Sciences University of Washington SeattleWA United States Impossible Foods Redwood CityCA United States

Joining biology with materials science requires the ability to design, engineer and control biology/solid-state materials interfaces at the molecular level. The specific molecular interactions that take place among biomolecules, known as molecular recognition, enable all aspects of molecular processes in living systems prerequisite to the biological functions. Having the ability to establish specific biological interactions between the solid materials and biological constituents is essential for precise design of biologically viable soft interfaces that are molecularly tailored at solid surfaces. Solid-binding peptides offer excellent opportunities in surface biofunctionalization over the traditionally utilized chemical approaches which generally make use of covalent bonds for surface molecular attachments with limited flexibility. Solid-binding peptides are selected using directed evolution techniques using genotype to phenotype relationships and therefore referred also as genetically engineered peptides for inorganics (GEPI) and exclusively bind to solid materials using molecular recognition. Here, the peptide has weak interactions at multiple contact points that are established between the biomolecule and the solid lattice, and then folds into a conformation coherent with the underlying solid lattice through self-organization on the surface. Solid-binding peptides provide an unprecedented biological advantage as modular building blocks to couple biological and synthetic entities at the bio–solid interfaces. Taking full advantage of biology's versatility, they can easily be engineered to form chimeric molecules with inherent multifunctionality displaying biofunctional molecular entities, such as enzymes, co-factors, antimicrobial peptides, antibodies, nucleic acids and molecular probes that target biomarkers. This minireview provides an insight into the key principles of solid-binding peptides for advancing surfaces biofunctionalization by a selected set of exampl

关键词： Biomolecules

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Controlled Release of Bone Morphogenetic Protein-2 Improves Motor Function after Traumatic Brain Injury in a Rat Model

SSRN

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SSRN 2025年

作者： Townsend, Jakob M. Deng, Jasmine Z. Barbay, Scott Andrews, Brian T. Nudo, Randolph J. Detamore, Michael S. C. Wayne McIlwraith Translational Medicine Institute Colorado State University Fort CollinsCO80523 United States School of Biomedical Engineering Colorado State University Fort CollinsCO80523 United States Bioengineering Graduate Program University of Kansas LawrenceKS66045 United States Department of Physical Medicine and Rehabilitation University of Kansas Medical Center Kansas CityKS66103 United States Department of Otolaryngology University of Iowa Medical Center Iowa CityIA52245 United States Department of Mechanical Engineering Colorado State University Fort CollinsCO80523 United States

Severe traumatic brain injury (TBI) is a life-threatening condition characterized by internal brain swelling and commonly treated using a two-stage surgical approach. The interval between surgeries, generally spaced weeks to months, is associated with secondary neurologic complications from leaving the brain unprotected. Hydrogels may reshape severe TBI treatment by enabling a single-stage surgical intervention, capable of being implanted at the initial surgery, remaining flexible to accommodate brain swelling, and calibrated to regenerate bone after brain swelling has subsided. The current study evaluated the use of a pentenoate-modified hyaluronic acid (PHA) polymer with thiolated devitalized tendon (TDVT) for calvarial bone regeneration in a rat TBI model. Additionally, PHA-TDVT hydrogels encapsulating microspheres containing bone morphogenetic protein-2 (BMP-2) were investigated to enhance bone regeneration. All hydrogel precursor formulations exhibited sufficient yield stress for surgical placement. The addition of TDVT to the crosslinked hydrogels increased the average compressive modulus. In vitro cell studies revealed that the PHA-TDVT hydrogel with the highest concentration of BMP-2 microspheres (i.e., PHA-TDVT+µ100) significantly improved calcium deposition and osteogenic gene expression. Minimal in vivo bone regeneration was observed for all hydrogel groups;however, BMP-2 microsphere addition fortuitously reduced motor skill impairment and brain atrophy. The PHA-TDVT+µ100 group had 2.8 times greater reach index and 2.3 times lower brain atrophy values compared to the negative control (p © 2025, The Authors. All rights reserved.

关键词： Transplantation (surgical)

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Linking physical phenotype to drug resistance: Single-cell mechanical measurements of acute promyelocytic Leukemia 23

Linking physical phenotype to drug resistance: Single-cell m...

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23rd International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2019

作者： Li, Brian L. Maslan, Annie M. Streets, Aaron M. Sohn, Lydia L. UC Berkeley UCSF Graduate Program in Bioengineering Berkeley and San Francisco United States UC Berkeley Center for Computational Biology Berkeley United States UC Berkeley Biophysics Graduate Group Berkeley United States UC Berkeley Department of Mechanical Engineering Berkeley United States

ISBN: (纸本)9781733419000

mechanical testing of cancer cells has established that certain pathophysiological phenotypes are strongly associated with abnormal cell mechanics. We used a microfluidic platform previously developed in our laboratory to perform rapid mechanical phenotyping of acute promyelocytic leukemia (APL) cells. These measurements revealed that drug-resistant APL cells exhibit more solid-like viscoelastic behavior compared to drug-responsive cells and that this mechanical difference could be due to chromatin condensation. Our work demonstrates that single-cell mechanical phenotyping could serve to predict drug-resistance in APL. © 2019 CBMS-0001.

关键词： mechanical testing

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Positive pressure testing booths development and deployment in response to the COVID-19 outbreak

arXiv

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arXiv 2021年

作者： Aroom, Kevin Ge, Jiawei White, Marcee Al-Zogbi, Lidia Trustman, Adrienne Greenbaum, Adena Krieger, Axel Farley, Jason Robert E. Fischell Institute for Biomedical Devices Department of Bioengineering University of Maryland College ParkMD20742 United States Laboratory for Computational Sensing and Robotics Department of Mechanical Engineering Johns Hopkins University BaltimoreMD21218 United States Robert E. Fischell Institute for Biomedical Devices Department of Mechanical Engineering University of Maryland College ParkMD20742 United States Total Health Care Inc. 1501 Division Street BaltimoreMD21217 United States Health Care for the Homeless 421 Fallsway BaltimoreMD21202 United States STI/HIV Program Baltimore City Health Department BaltimoreMD21202 United States The REACH Initiative Johns Hopkins University School of Nursing BaltimoreMD21205 United States

The COVID-19 pandemic left an unprecedented impact on the general public health, resulting in thousands of deaths in the US alone. Nationwide testing plans were initiated to control the spread, with drive-through being the currently dominant testing approach, which, however, exhausts personal protective equipment supplies, and is unfriendly to individuals not owning a vehicle. Walk-up testing booths are a safe alternative, but are too prohibitively priced on the market to allow for nationwide deployment. In this paper, we present an accessible, mobile, affordable, and safe version of a positive-pressure COVID-19 testing booth. The booths are manufactured using primarily off-the-shelf components from US vendors with minimized customization. The booths’ mobility allows them to be easily transported within local communities to test a larger subset of the population with fewer transportation options. Moreover, the final bill of materials does not surpass USD 3,900, which is about half of the market price. The booths are air conditioned and HEPA filtered to offer healthcare providers a safe and comfortable working environment. The prototype passed required pressure and air exchange tests, and was positively reviewed by two healthcare professionals. Currently, five booths are deployed and used at the Johns Hopkins University School of Nursing, Baltimore City Health department, and two community health centers in Baltimore. Our design facilitates walk-up testing in the US, as it decreases PPE consumption;reduces the risk of infection;and is accessible to lower-income communities and non-drivers. © 2021, CC BY-SA.

关键词： Air conditioning

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