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The innate regenerome: Harnessing mesenchymal niches and engineered cytotoxic killers for solid tumor immunotherapy.

Solid tumors evade adaptive immunity through MHC class I downregulation, stromal barricades, and T-cell exhaustion, rendering conventional immunotherapies ineffective in "cold" lesions. This review introduces the Innate Regenerome, a unified framework harnessing mesenchymal stromal cells (MSCs), CAR-engineered natural killer (CAR-NK) cells, and CAR-macrophages (CAR-M) to simultaneously eliminate malignancy and restore tissue architecture. MSCs serve as switchable niche engineers, delivering logic-gated anti-fibrotic and chemotactic cues. CAR-NK cells provide rapid, non-exhaustible cytotoxicity

Engineered Probiotics Secreting IL-18BP and Armed with Dual Single-Atom Catalysts for Synergistic Therapy in Ulcerative Colitis.

Ulcerative Colitis (UC) involves a complex pathological process characterized by excessive reactive oxygen species (ROS) production at lesion sites and gut microbiota dysregulation. Conventional therapies are often limited by their inability to concurrently address oxidative stress, immune dysregulation, and microbial imbalance. Herein, we developed an integrated bionanoplatform (DEI) by conjugating dual single-atom catalysts (DACs) with an engineered probiotic strain, Escherichia coli Nissle 1917 (EcN). This EcN was genetically modified to stably express interleukin-18 binding protein (IL-18B

FLT201, a novel liver-directed AAV gene therapy candidate for Gaucher disease type 1.

Gaucher disease type 1 (GD1) is caused by mutations in the GBA1 gene, which result in deficient enzyme β-glucocerebrosidase (GCase) activity and production with the harmful accumulation of the lipid substrate glucocerebroside. Replacement of GCase is current standard of care for GD1; however, GCase has a relatively short active half-life at both physiological and lysosomal pH and biweekly intravenous administration does not provide a consistent exposure to active enzyme. FLT201 is the first adeno-associated virus (AAV) gene therapy in clinical trials for treatment of GD1. FLT201 consists of a

Проектирование микробиома: новый подход к лечению аутоиммунных заболеваний.

Аутоиммунные заболевания возникают в тех случаях, когда иммунная система ошибочно наносит удар по собственным тканям тела, поражая миллионы людей и часто требуя длительного лечения. Текущая терапия, такая, как иммунодепрессанты и биологика, помогает справляться с симптомами, но может вызывать серьезные побочные эффекты. Обнадеживающий новый подход предполагает использование метода микробиота, который изменяет кишечную бактерию, чтобы повлиять на иммунную функцию и потенциально облегчить аутоиммунные условия. Микробиом кишечника имеет решающее значение для регулирования иммунитета, и дисбаланс

Photosynthetic medicine: Engineering a plant-derived nanofoundry to power mammalian cells.

Mammalian eyes receive constant visible light yet lack photosynthesis. Xing et al. engineer an intact thylakoid grana nanoparticle enabling light-driven NADPH production within corneal cells, restoring antioxidant defenses and interrupting inflammatory cycles in dry eye disease. This work positions borrowed photosynthesis as a therapeutic strategy for oxidative, light-exposed tissue pathologies.

Cell-based passive immunization for protection against SARS-CoV-2 infection.

BACKGROUND: Immunologically impaired individuals respond poorly to vaccines, highlighting the need for additional strategies to protect these vulnerable populations from COVID-19. While monoclonal antibodies (mAbs) have emerged as promising tools to manage infectious diseases, the transient lifespan of neutralizing mAbs in patients limits their ability to confer lasting, passive prophylaxis from SARS-CoV-2. Here, we attempted to solve this problem by combining cell and mAb engineering in a way that provides durable immune protection against viral infection using safe and universal cell therapy

A 3D-Printed Vascular-Like Perfusion Tumor-on-a-Chip Recapitulates High-Grade Breast Cancer With in Vivo-Relevant Drug Resistance.

Tumor progression and drug resistance in breast cancer are fundamentally governed by a complex microenvironment, characterized by extreme cell densities and associated nutrient/oxygen gradients. Conventional in vitro models often fail to replicate these features due to mass transport limitations in non-perfused systems. Here, we present a next-generation tumor-on-a-chip platform engineered via high-resolution projection micro-stereolithography (PµSL) to sustain exceptionally high-density breast cancer tissues (up to 400 million cells/mL) under continuous perfusion. By integrating a vascular-in

Construction of Multilayered Biomimetic Blood Vesselwith BiphasicCellular System Viapre-StressedBioprinting.

Blood vessels are distributed throughout all tissues/organs in the human body, serving as a prerequisite for their survival. Vascular stenosis and rupture caused by disease, trauma, or congenital factors often lead to ischemic necrosis of tissues/organs, which can be life-threatening in severe cases. Engineered biomimetic blood vessels are extensively studied as potential replacements for diseased vessels. However, current research has not yet perfectly integrated vascular structure, spatial distribution, and the arrangement of multi-type cells. Herein, pre-stressed bioprinting is employed to

Engineering a functionality-integrated artificial cornea stromal Substitute: Janus bio-adhesive implant with a collagen-based multi-scale biomimetic skeleton.

Corneal transplantation presents an urgent demand for artificial cornea stromal substitutes (ACSs) with comprehensive functional design, spanning from material biology to clinical application. Here, we report the use of an engineering integration strategy to develop Janus ACSs with collagen-based multiscale biomimetic skeletons and tissue-adhesion. Specifically, the electro-assembly of collagen is employed to construct the skeleton of Janus ACS that mimics the microstructure and macroscopic morphology of native corneal stroma, ensuring the desired transparency, refractive power and adaptable s

Current microfluidic platforms for reverse engineering of cornea.

According to the World Health Organization, corneal blindness constitutes 5.1% of global blindness population. Surgical outcomes have been i … es for constructing physiologically representative corneal models. With significant improvements in tissue engineering technology, CoC integrates corneal cells with microfluidics to recapitulate human corneal microenvironment for the study of corneal pathophysiological changes and evaluation of ocular drugs. Such model, in complement to animal studies, can potential …

Matrix-associated chondrocyte transplantation for reconstruction of articulating surfaces in the temporomandibular joint: a pilot study covering medium- and long-term outcomes of 6 patients.

OBJECTIVE: Matrix-associated chondrocyte transplantation is routinely used in joints of the extremities but not in the temporomandibular joint (TMJ). STUDY DESIGN: We report the first case series in 7 patients of a tissue engineering approach to regenerate severely degraded articulating surfaces in the TMJ by simultaneously completely resurfacing both the mandibular condyle and the articular eminence/glenoid fossa with a commercially available collagen sponge seeded with autologous cells stabilized within a fibrin matrix. To facilitate healing, we temporarily employed a silicone membrane to p…

Transgenic rice (Oryza sativa) endosperm expressing daffodil (Narcissus pseudonarcissus) phytoene synthase accumulates phytoene, a key intermediate of provitamin A biosynthesis.

Rice (Oryza sativa L.), the major food staple for more than two billion people, contains neither beta-carotene (provitamin A) nor C40 carotenoid precursors thereof in its endosperm. To improve the nutritional value of rice, genetic engineering was chosen as a means to introduce the ability to make beta-carotene into rice endosperm tissue. Investigation of the biochemical properties of immature rice endosperm using [14C]-labelled substrates revealed the presence of geranyl geranyl diphosphate, the C20 general isoprenoid precursor necessary for C40 carotenoid biosynthesis. Phytoene synthase, whi

XCM Biologic Tissue Matrix xenograft and autologous micromucosa graft for vaginal reconstruction in Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome can be treated through numerous surgical and nonsurgical methods. We present a surgical technique in which a neovagina was reconstructed and shaped by a vaginal expander with acellular porcine dermal matrix (XCM Biologic Tissue Matrix) and mucosal interposition using microfragments harvested from the hymen. In our case, we found this procedure to be safe and effective, resulting in satisfactory sexual function and good cosmetic results, without donor site morbidity. To our best knowledge, this tissue-engineered biomaterial has never been used for

Tracking of leukocyte recruitment into tissues of mice by in situ labeling of blood cells with the fluorescent dye CFDA SE.

Models of inflammatory and immune diseases are extensively studied in mice with engineered genetic mutations, and tracking the recruitment of blood leukocytes into tissues is an important component of these studies. A direct in situ method for labeling the total pool of blood cells in mice by a single intravenous injection of the fluorescent dye CFDA SE (CFSE) is described. The fluorescence intensity of labeled cells initially declines, but remains stable after 4 h, enabling detection weeks after labeling. Labeled leukocytes can be tracked as they accumulate in lymphoid tissues and sites of in

From biological surfaces to engineered systems: how synthetic and systems biology enable biomimetic design.

Biological surfaces perform a wide range of functions, including communication, molecular exchange, defense, and movement. While these architectures have long inspired biomimetic surface engineering, most existing reviews focus on fabrication methods, often overlooking the biological mechanisms underlying the functions. This review examines how the structural and functional properties of biological surfaces can inform the design of advanced biomimetic systems. Using an integrative framework combining systems and synthetic biology, we establish key design principles derived from biological surf

Evaluation of an engineered vascular graft exhibiting somatic growth in lambs to model repair of absent pulmonary artery branch.

BACKGROUND: Growth is the holy grail of tissue implants in pediatrics. No vascular graft currently in use for surgical repairs of congenital heart defects has somatic growth capacity. METHODS: Biologically-engineered grafts (6 mm) grown from donor ovine fibroblasts in a sacrificial fibrin gel were implanted into the left pulmonary branch of 3-month old lambs for 3, 6, and 18 months. A control group of Propaten® PTFE grafts was implanted for 6 months. RESULTS: The engineered grafts exhibit extensive site-appropriate recellularization after only 3 months and near-normal increase of diameter fr

Antibacterial Fusion Protein BPI21/LL-37 Modification Enhances the Therapeutic Efficacy of hUC-MSCs in Sepsis.

Sepsis, which is characterized by multiple organ dysfunctions as a result of an unbalanced host-inflammatory response to pathogens, is potentially a life-threatening condition and a major cause of death in the intensive care units (ICUs). However, effective treatment or intervention to prevent sepsis-associated lethality is still lacking. Human umbilical cord mesenchymal stem cell (hUC-MSC) transplantation has been shown to have potent immunomodulatory properties and improve tissue repair yet lacks direct antibacterial and endotoxin clearance activities. In this study, we engineered hUC-MSCs t

Advances in Hydrogel - Mesenchymal Stem Cells Composites for Accelerating Burn Wound Repair.

Burn wounds (BWs) are common severe clinical traumas prone to life-threatening complications like infections and sepsis, often causing permanent scarring and skin dysfunction that severely impact quality of life, remaining a major challenge in trauma treatment. As promising biomaterials, hydrogels are widely used in tissue engineering for their excellent biocompatibility, controllable degradability, high water content, and 3D porous structure. They mimic the extracellular matrix (ECM) to support cell growth and efficiently load/sustainably release bioactive components such as mesenchymal stem …

Next-Generation Hydrogel Skin Adhesives: From Bioinspired Adhesion Chemistry to Regenerative Wound Interfaces.

Hydrogel-based skin adhesives have emerged as promising alternatives to conventional wound-closure methods such as sutures and staples because they can establish conformal contact with soft, irregular, and wet tissue surfaces. Recent advances in polymer chemistry and biointerface engineering have enabled the development of hydrogel adhesives that combine strong wet adhesion with mechanical compliance, cytocompatibility, and therapeutic functionality. In this review, we summarize recent progress in the design of hydrogel-based skin adhesives, with particular emphasis on the chemical and interfa

Терапевтический потенциал моделей Purmorphamine через болезни.

Purmorphamine (PUR) — тройная субституция пурина, которая выборочно активирует сгущенный рецептор, тем самым инициируя Sonic Hedgehog (Shhh) сигнализирующий путь, имеющий решающее значение для эмбриональной модели, нейронной спецификации и регенерации тканей в различных системах различных органов. Регулирование сигнала " Шш " причастно к дегенеративным заболеваниям, однако терапевтические меры, направленные на этот путь, по-прежнему ограничены. PUR демонстрирует широкую терапевтическую эффективность различных моделей предклинических заболеваний путем активации как транскрипции с помо

Совпадение в аннотации оригинала
Purmorphamine (PUR) is a trisubstituted purine compound that selectively activates Smoothened receptor, thereby initiating Sonic Hedgehog (S … estores myelin integrity in multiple sclerosis models and drives osteogenic differentiation in bone tissue engineering applications. Beyond its established Smoothened agonist activity, recent evidence identifies PUR as a positive allosteric modulator of the secretin receptor, expanding its therapeutic scope to include cardiovascular applications such as hypertension …