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The Rise of Mechanobiology for Advanced Cell Engineering and Manufacturing

The rise of cell-based therapies, regenerative medicine, and synthetic biology, has created an urgent need for efficient cell engineering, which involves the manipulation of cells for specific purposes. This demand is driven by breakthroughs in cell manufacturing, from fundamental research to clinical therapies. These innovations have come with a deeper understanding of developmental biology, continued optimization of mechanobiological processes and platforms, and the deployment of advanced biotechnological approaches. Induced pluripotent stem cells and immunotherapies like chimeric antigen receptor T cells enable personalized, scalable treatments for regenerative medicine and diseases beyond oncology. But continued development of cell manufacturing and its concomitant clinical advances is hindered by limitations in the production, efficiency, safety, regulation, cost-effectiveness, and scalability of current manufacturing routes. Here, recent developments are examined in cell engineering, with particular emphasis on mechanical aspects, including biomaterial design, the use of mechanical confinement, and the application of micro-and nanotechnologies in the efficient production of enhanced cells. Emerging approaches are described along each of these avenues based on state-of-the-art fundamental mechanobiology. It is called on the field to consider mechanical cues, often overlooked in cell manufacturing, as key tools to augment or, at times, even to replace the use of traditional soluble factors.


Current manufacturing workflows for CAR-based immunotherapies, particularly CAR T, and the emerging CAR NK and CAR macrophage platforms, generally involve four key stages: (i) isolation of primary immune cells or their precursors, (ii) cell activation or differentiation, (iii) genetic modification with CAR constructs, most often via viral vectors or electroporation (EP), and (iv) expansion or preparation for reinfusion. Among these, transfection remains the most critical and technically challenging step, directly influencing the functionality, safety, and scalability of the final product.

In clinical-scale production, EP remains the most widely used non-viral method for gene delivery into immune cells, yet it is increasingly recognized as suboptimal, particularly when delivering large or complex CAR constructs. It suffers from inefficient nuclear delivery, high cell toxicity, and poor functional yields of viable, potent CAR-expressing cells.[ 113 ] These limitations are further exacerbated in more fragile or less permissive cell types, such as NK cells and macrophages, which show lower transfection efficiencies and greater sensitivity to electroporation-induced stress.[ 114 ] Viral vectors, while still dominant in clinical manufacturing, present their own challenges: they are constrained by limited cargo capacity, are costly to produce at scale, and raise regulatory and safety concerns, especially when applied to emerging CAR-NK and CAR macrophage therapies that require flexible, transient, or multiplexed genetic programs.[ 115 ]

In contrast to immune-cell engineering, stem cell-based approaches present a different set of challenges and engineering requirements. While immune cells are genetically modified to enhance cytotoxicity[ 116 ] and specificity or to mitigate excessive T-cell activation,[ 117 ] stem cells must be engineered to control self-renewal, lineage commitment, and functional integration, often requiring precise, non-integrative delivery of genetic or epigenetic modulators (e.g., mRNA, episomal vectors) to maintain cellular identity and safety.[ 118 ] Stem cells hold exceptional therapeutic promise due to their capacity for self-renewal and differentiation into specialized cell types, supporting applications in personalized disease modeling, tissue repair, and organ regeneration.[ 119 ] However, engineering stem cells in a safe, efficient, and clinically relevant manner remains a major challenge. Conventional delivery methods, such as viral vectors and EP, can compromise genomic integrity,[ 120 ] reduce viability,[ 118 ] and induce epigenetic instability,[ 121 ] limiting their translational potential.

‘Molecular dam’ stops energy leaks in nanocrystals to boost efficiency of light-driven reactions

A team of scientists has found a way to slow energy leaks that have impeded the use of tiny nanocrystals in light-driven chemical and energy applications.

As described in an article published in the journal Chem, the team has used a molecule that strongly binds to the nanocrystal’s surface, essentially acting like a dam to hold back the energy stored in the charge-separated state formed after light absorption. This technique extends the lifetime of the charge separation to the longest recorded for these materials, providing a pathway to improved efficiencies and more opportunities to put this energy to work in chemical reactions.

The researchers from the University of Colorado Boulder, the University of California Irvine, and Fort Lewis College were led by RASEI Fellow Gordana Dukovic.

Shape memory polymers with nanotips help solve micro-LED chip transfer problem

A research team at Pohang University of Science and Technology (POSTECH), has developed a novel dry adhesive technology that allows everything from microscale electronic components to common household materials to be easily attached and detached.

The study was recently published in the journal Nature Communications, and the team was led by Professor Seok Kim in collaboration with Professor Kihun Kim (POSTECH), Professor Namjoong Kim (Gachon University), Professor Haneol Lee (Chonbuk National University), and Dr. Chang-Hee Son (University of Connecticut, U.S.).

Micro-LEDs, a next-generation display technology, offer significant advantages such as higher brightness, longer lifespan, and the ability to enable flexible and transparent displays. However, transferring micro-LED chips—thinner than a strand of hair—onto target substrates with high precision and minimal residue has been a persistent challenge. Conventional methods relying on liquid adhesives or specialized films often result in overly complex processes, poor alignment accuracy, and residual contamination.

Revolutionary Prosthetic Eye Chip Restores Sight in Medical First

A tiny chip implanted into the eyes of people suffering vision loss from irreversible age-related macular degeneration has restored central sight in a dazzling first.

It’s called the PRIMA system, tested across 17 European hospitals, and it restored central vision in 26 of 32 patients who used it for 12 months – many of whom could even read again. The result, developed by a large international team of doctors and scientists over many years, represents a massive breakthrough in treatments for vision loss.

“It’s the first time that any attempt at vision restoration has achieved such results in a large number of patients,” says ophthamologist José-Alain Sahel of the University of Pittsburgh School of Medicine, co-senior author on a paper describing the results.

Stem Cells Age Ten Times Faster in Space, New Study Finds

Traveling to space presents significant challenges to human health, with research detailing a variety of detrimental effects on the body that may mirror accelerated aging. These include a loss of bone density, swelling of brain and eye nerves, and changes in gene expression. NASA’s groundbreaking study featuring identical twin astronauts Mark and Scott Kelly provided vital insights into these concerns by observing Scott’s physical condition after spending 340 days in space, while Mark remained on Earth. Findings from this 2019 “twins study,” published in the journal Science, revealed that Scott experienced DNA damage, cognitive decline, and persistent telomere shortening—an indication of aging—even six months post-mission.

Recent research has now uncovered an alarming revelation about stem cells during spaceflight, indicating that they exhibit signs of aging at a staggering rate—up to ten times faster than their counterparts on Earth. Dr. Catriona Jamieson, director of the Sanford Stem Cell Institute at the University of California, San Diego, and a lead author of the new study published in the journal Cell Stem Cell, articulated the significance of this finding. Stem cells, which are crucial for the development and repair of various tissues, losing their youthful capacity could lead to grave health issues, such as chronic diseases, neurodegeneration, and cancer.

This study arrives at a pivotal moment, as both government agencies and private companies are gearing up for long-duration missions to the moon and beyond. With the surge in interest in spaceflight, understanding the associated health risks has never been more urgent. Insights from this accelerated cellular aging could not only inform safer space travel but also enhance our understanding of biological processes on Earth.

Retinal implant restores central vision in patients with advanced AMD, study shows

A wireless retinal implant can restore central vision in patients with advanced age-related macular degeneration (AMD), according to clinical trial results published in the New England Journal of Medicine.

Advanced atrophic AMD, also known as geographic atrophy (GA), is the leading cause of irreversible blindness in , affecting more than 5 million people worldwide.

The international, multi-center trial was co-led by José-Alain Sahel, M.D., director of the UPMC Vision Institute, Daniel Palanker, Ph.D., professor of ophthalmology at Stanford University, and Frank Holz, M.D., professor of ophthalmology at the University of Bonn, Germany.

MRI age clocks reveal how each organ ages differently and predict who develops disease or lives longer

Researchers developed seven MRI-based biological age clocks across major organs using UK Biobank imaging, linking each to proteins, metabolites, genetics, disease risks, mortality, and cognitive decline. These organ-specific age gaps reveal how uneven aging shapes vulnerability to conditions such as diabetes, hypertension, and dementia, opening new paths for precision prevention and clinical trial stratification

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