In Vivo Testing of Engineered Tissues

𝗘𝗻𝗴𝗶𝗻𝗲𝗲𝗿𝗲𝗱 𝗵𝗲𝗮𝗿𝘁 𝗺𝘂𝘀𝗰𝗹𝗲 𝗮𝗹𝗹𝗼𝗴𝗿𝗮𝗳𝘁𝘀 𝗳𝗼𝗿 𝗵𝗲𝗮𝗿𝘁 𝗿𝗲𝗽𝗮𝗶𝗿 𝗶𝗻 𝗽𝗿𝗶𝗺𝗮𝘁𝗲𝘀 𝗮𝗻𝗱 𝗵𝘂𝗺𝗮𝗻𝘀 Cardiomyocytes can be implanted to remuscularize the failing heart. Challenges include sufficient cardiomyocyte retention for a sustainable therapeutic impact without intolerable side effects, such as arrhythmia and tumour growth. The authors investigated the hypothesis that epicardial engineered heart muscle (EHM) allografts from induced pluripotent stem cell-derived cardiomyocytes and stromal cells structurally and functionally remuscularize the chronically failing heart without limiting side effects in rhesus macaques. After confirmation of in vitro and in vivo (nude rat model) equivalence of the newly developed rhesus macaque EHM model with a previously established Good Manufacturing Practice-compatible human EHM formulation, long-term retention (up to 6 months) and dose-dependent enhancement of the target heart wall by EHM grafts constructed from 40 to 200 million cardiomyocytes/stromal cells were demonstrated in macaques with and without myocardial infarction-induced heart failure. In the heart failure model, evidence for EHM allograft-enhanced target heart wall contractility and ejection fraction, which are measures for local and global heart support, was obtained. Histopathological and gadolinium-based perfusion magnetic resonance imaging analyses confirmed cell retention and functional vascularization. Arrhythmia and tumor growth were not observed. The obtained feasibility, safety and efficacy data provided the pivotal underpinnings for the approval of a first-in-human clinical trial on tissue-engineered heart repair. The present clinical data confirmed remuscularization by EHM implantation in a patient with advanced heart failure. https://lnkd.in/g_iAuZNi

German scientists have created a tiny 3D printer that can build living tissue inside the human body. The system uses a microscopic lens smaller than a grain of salt, attached to an optical fiber, to guide light and solidify bioinks into precise structures. Unlike most conventional bioprinters that operate outside the body, this device can be inserted through an endoscope, enabling direct, minimally invasive tissue fabrication. By printing cells and biodegradable materials exactly where they are needed—rather than growing tissue externally and transplanting it later—researchers can potentially repair or rebuild damaged organs with unprecedented precision. The technology’s micrometer-scale accuracy opens the door to in-body printing of vascular structures, cartilage, or even neural tissue, marking a step toward true on-demand organ repair.

🚨 What If Surgeons Became Obsolete? Scientists at Caltech just 3D-printed inside a living body — without cutting the skin. And it’s not sci-fi anymore. Forget scalpels. Forget long hospital stays. This is bioprinting through sound waves — real structures formed deep inside living tissue using focused ultrasound. Here’s what’s actually happening: • Researchers inject a liquid bio-ink into the body — loaded with temperature-sensitive carriers that release crosslinking molecules only when ultrasound heats them slightly. • A focused ultrasound beam raises the temperature by just a few degrees — triggering the ink to solidify into a polymer or hydrogel exactly where needed. • The process is guided and monitored in real time using ultrasound imaging — no incisions, no internal cameras. So far, scientists have successfully printed: ✔ Polymer structures for drug delivery and wound sealing ✔ Hydrogels that could one day become tissues or scaffolds inside organs ✔ Even bioelectric materials for sensing internal physiology — all without surgery. 🔥 Here’s the provocative part: If we can manufacture structures inside a beating heart or damaged liver without surgery, what happens to: ➡ Traditional surgery? ➡ Surgical training pathways? ➡ The entire multimillion-dollar implant industry? This is NOT future talk — it’s real research published in Science and led by engineers who used ultrasound the way others use a printer nozzle. 🎯 Discussion Starter: Where do YOU think this technology will hit first — cancer therapy? Organ repair? Replacing pacemakers? Or printed nerve networks? 👇 Drop your boldest prediction. 📚 Sources • California Institute of Technology (Caltech) – 3D Printing In Vivo Using Sound • IEEE Spectrum – Bioprinting Inside the Body Using Ultrasound • Nature Materials (research publication referenced by Caltech)

Researchers at Cincinnati Children’s Hospital, working with Japanese scientists, have made a major breakthrough in organ engineering: they’ve created lab-grown liver tissue that forms its own blood vessels. This solves one of the biggest challenges in building transplantable organs — how to keep them alive and functioning with proper blood flow. The team used induced pluripotent stem cells (iPSCs) and a special air-liquid interface culture system to grow a self-assembling liver organoid. This mini liver formed its own sinusoid-like vessels — tiny channels that can circulate fluid — and started producing clotting proteins, including Factor VIII. When tested in mouse models of hemophilia A, a disease that causes severe bleeding, the vascularized liver tissue corrected the bleeding symptoms, showing that it worked like a real organ. This advancement brings the medical world one step closer to creating fully functional, transplant-ready organs in the lab. #LiverOrganoid #TissueEngineering #RMScienceTechInvest

An excellent work to develop in vivo CAR-T using AAV engineering platform, which may be a safer, avoid unexpected integration using LVV vectors An AAV variant enables human T cell engineering in vivo Here, we show that an engineered AAV6 variant, AAV6-M2, can enable in vivo CAR expression in human T cells following systemic administration in a Humanized Immune System (HIS) mouse model. AAV6-M2-CD19CAR turned up to 77.5% of human CD8+ T cells into CAR-T cells across multiple organs six weeks post-AAV injection. In HIS mice exhibiting systemic lupus erythematosus (SLE)-like symptoms, AAV6-M2-CD19CAR treatment effectively depleted B cells in both peripheral blood and tissues, accompanied by improved lupus pathologies. Importantly, systemic delivery of AAV6-M2 resulted in significant liver de-targeting, with viral genome levels in the liver reduced by over two orders of magnitude in both mice and cynomolgus macaque compared to the wild-type AAV. Through CRISPR screening, cryo-EM structural analysis, and molecular docking, we identified CD62L as a key mediator of AAV6-M2's enhanced transduction to human T cells, enabling CAR delivery without the need for prior T cell activation. These findings established that AAV-mediated CAR delivery can generate functional human CAR-T cells in vivo, with mechanistic insights into the selective targeting of T cells. This work highlights engineered AAV vectors as a promising platform for in vivo CAR-T therapy and expands the therapeutic landscape of AAV beyond inherited diseases. https://lnkd.in/eRequWy2