Search Results (337)

Approximately 185,000 people in the United states experience limb loss each year. There is a need for an intuitive neural interface that can offer high-fidelity control signals to optimize the advanced functionality of prosthetic devices. Regenerative peripheral nerve interface (RPNI) is a pioneering advancement in neuroengineering that combines surgical techniques with biocompatible materials to create an interface for individuals with limb loss. RPNIs are surgically constructed from autologous muscle grafts that are neurotized by the residual peripheral nerves of an individual with limb loss. RPNIs amplify neural signals and demonstrate long term stability. In this narrative review, the terms “Regenerative Peripheral Nerve Interface (RPNI)” and “RPNI surgery” are used interchangeably to refer to the same surgical and biological construct. This narrative review specifically focuses on RPNIs as a targeted approach to enhance prosthetic control through surgically created nerve–muscle interfaces. This area of research offers a promising solution to overcome the limitations of existing prosthetic control systems and could help improve the quality of life for people suffering from limb loss. It allows for multi-channel control and bidirectional communication, while enhancing the functionality of prosthetics through improved sensory feedback. RPNI surgery holds significant promise for improving the quality of life for individuals with limb loss by providing a more intuitive and responsive prosthetic experience. Full article

Cucumbers (Cucumis sativus L.) are highly sensitive to cold, but grafting onto cold-tolerant rootstocks can enhance their low-temperature resilience. This study investigates the physiological and molecular mechanisms by which exogenous vitamin C (Vc) mitigates cold stress in grafted cucumber seedlings. Using cucumber ‘Chiyu 505’ as the scion and pumpkin ‘Chuangfan No.1’ as the rootstock, seedlings were grafted using the whip grafting method. In the third true leaf expansion stage, seedlings were foliar sprayed with Vc at concentrations of 50, 100, 150, and 200 mg L⁻¹. Three days after initial spraying, seedlings were subjected to cold stress (8 °C) for 3 days, with continued spraying. After that, morphological and physiological parameters were assessed. Results showed that 150 mg L⁻¹ Vc treatment was most impactive, significantly reducing the cold damage index while increasing the root-to-shoot ratio, root vitality, chlorophyll content, and activities of antioxidant enzymes (SOD, POD, CAT). Moreover, this treatment enhanced levels of soluble sugars, soluble proteins, and proline compared to control. However, 200 mg L⁻¹ treatment elevated malondialdehyde (MDA) content, indicating potential oxidative stress. For transcriptomic analysis, leaves from the 150 mg L⁻¹ Vc and CK treatments were sampled at 0, 1, 2, and 3 days of cold stress. Differential gene expression revealed that genes associated with photosynthesis (LHCA1), stress signal transduction (MYC2-1, MYC2-2, WRKY22, WRKY2), and antioxidant defense (SOD-1, SOD-2) were initially up-regulated and subsequently down-regulated, as validated by qRT-PCR. Overall, we found that the application of 150 mg L⁻¹ Vc enhanced cold tolerance in grafted cucumber seedlings by modulating gene expression networks related to photosynthesis, stress response, and the antioxidant defense system. This study provides a way for developing Vc biostimulants to enhance cold tolerance in grafted cucumbers, improving sustainable cultivation in low-temperature regions. Full article

The indications for immune checkpoint inhibitor (ICI) use in cancer treatment continue to expand. This is attributable to their proven anticancer activity in addition to their tolerability and favorable toxicity profile as compared to conventional chemotherapeutic agents. ICIs work by blocking the inhibitory signals between tumor cells and T-cells, thereby enhancing the T-cell cytotoxic activity to inhibit tumor growth. Because of their immune-stimulating effect, ICIs are linked to adverse renal outcomes in both native and transplanted kidneys. The risk of kidney allograft rejection in the setting of ICI use has been reported to be around 40%, leading to an increased risk of graft loss. In this report, we review the literature examining outcomes in kidney transplant recipients receiving ICIs for various oncologic indications. Full article

Grafting involves complex hormonal interactions at graft interfaces that are not yet fully understood. In this study, we analyzed hormone fluctuations and gene expression during callus proliferation and vascular tissue differentiation in hickory (Carya cathayensis Sarg.) grafts. Cytokinin and ethylene precursor ACC levels steadily increased after grafting. The biosynthetic genes for these hormones (IPT3, ACS1, ACO1, and ACO5) exhibited heightened expression. Genes related to cytokinin signaling (RR3, ARR4, and ZFP5) and ethylene signaling (MKK9, ESE1, and ESE3) were similarly upregulated. Conversely, genes associated with jasmonic acid, abscisic acid, and strigolactone pathways were downregulated, including synthesis genes (AOC4 and AOS) and those involved in signal transduction (NAC3, WRKY51, and SMAX1). Correspondingly, JA-Ile and 5-deoxystrigol levels significantly decreased. Indole-3-acetic acid (IAA) levels also dropped during the early stages of graft union formation. These results suggest that low auxin concentrations may be essential in the initial stages after grafting to encourage callus proliferation, followed by an increase at later stages to facilitate vascular bundle differentiation. These findings imply that maintaining a balance between low auxin levels and elevated cytokinin and ethylene levels may be critical to support cell division and callus formation during the initial proliferation phase. Later, during the vascular differentiation phase, a gradual rise in auxin levels, accompanied by elevated ethylene, may facilitate the differentiation of vascular bundles in hickory grafts. Full article

Background/Objectives: Organ transplantation is a life-saving intervention for patients with terminal organ failure, but long-term success is hindered by graft rejection and dependence on lifelong immunosuppressants. These drugs pose risks such as opportunistic infections and malignancies. Chimeric antigen receptor (CAR) technology, originally developed for cancer immunotherapy, has been adapted to regulatory T cells (Tregs) to enhance their antigen-specific immunosuppressive function. This systematic review evaluates the preclinical development of CAR-Tregs in promoting graft tolerance and suppressing graft-versus-host disease (GvHD). Methods: A systematic review following PROSPERO guidelines (CRD420251073207) was conducted across PubMed, Scopus, and Web of Science for studies published from 2015 to 2024. After screening 105 articles, 17 studies involving CAR-Tregs in preclinical or in vivo transplant or GvHD models were included. Results: CAR-Tregs exhibited superior graft-protective properties compared to unmodified or polyclonal Tregs. HLA-A2-specific CAR-Tregs consistently improved graft survival, reduced inflammatory cytokines, and suppressed immune cell infiltration across skin, heart, and pancreatic islet transplant models. The inclusion of CD28 as a co-stimulatory domain enhanced Treg function and FOXP3 expression. However, challenges such as Treg exhaustion, tonic signaling, and reduced in vivo persistence were noted. Some studies reported synergistic effects when CAR-Tregs were combined with immunosuppressants like rapamycin or tacrolimus. Conclusions: CAR-Tregs offer a promising strategy for inducing targeted immunosuppression in allogeneic transplantation. While preclinical findings are encouraging, further work is needed to optimize CAR design, ensure in vivo stability, and establish clinical-scale manufacturing before translation to human trials. Full article

Vein graft restenosis remains a major complication following coronary artery bypass grafting (CABG), mainly due to the abnormal proliferation of vascular smooth muscle cells (VSMCs) and impaired endothelial repair. While external stents (eStents) can provide mechanical support and limit adverse remodeling, traditional metallic stents are non-degradable and may induce chronic inflammation and fibrosis. In contrast, many bioresorbable materials degrade too quickly or lack mechanical strength. These challenges highlight the need for external stents that combine sufficient mechanical strength with biodegradability to support long-term graft patency. This is the first study that develops a chlorogenic acid–strontium (SrCA)-loaded polycaprolactone bioresorbable eStent that inhibits VSMC proliferation and enhances endothelial repair via Hippo–Yes-associated protein (YAP) signaling, addressing vein graft restenosis post-CABG. Combining mechanical support and biodegradability, it overcomes the limitations of non-degradable stents and rapidly degrading biomaterials, elucidates the potential of natural polyphenol–metal ion complexes in vascular remodeling, and offers an innovative strategy for the prevention of vein graft restenosis. Full article

This study develops a one-pot anodic templating electrodeposition strategy using dual-cation-crosslinking and interpenetrating networks, coupled with pulsed electrical signals, to fabricate a vessel-mimetic multilayered tubular hydrogel. Typically, the anodic electrodeposition is performed in a mixture of sodium alginate (SA) and carboxymethyl chitosan (CMC), with the ethylenediaminetetraacetic acid calcium disodium salt hydrate (EDTA·Na₂Ca) incorporated to provide a secondary ionic crosslinker (i.e., Ca²⁺) and modulate the cascade reaction diffusion process. The copper wire electrodes serve as templates for electrochemical oxidation and enable a copper ion (i.e., Cu²⁺)-induced tubular hydrogel coating formation, while pulsed electric fields regulate layer-by-layer deposition. The dual-cation-crosslinked interpenetrating hydrogels (CMC/SA-Cu/Ca) exhibit rapid growth rates and tailored mechanical strength, along with excellent antibacterial performance. By integrating the unique pulsed electro-fabrication with biomimetic self-assembly, this study addresses challenges in vessel-mimicking structural complexity and mechanical compatibility. The approach enables scalable production of customizable multilayered hydrogels for artificial vessel grafts, smart wound dressings, and bioengineered organ interfaces, demonstrating broad biomedical potential. Full article

Graft-versus-host disease (GVHD) remains a significant barrier to the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), contributing to long-term morbidity and non-relapse mortality in both pediatric and adult populations. Central to GVHD pathophysiology is the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, where JAK2 mediates key pro-inflammatory cytokines, including IL-6, IFN-γ, and GM-CSF. These cytokines promote donor T cell activation, effector differentiation, and target organ damage. The introduction of ruxolitinib, a selective JAK1/2 inhibitor, has transformed the treatment landscape for steroid-refractory acute and chronic GVHD, leading to improved response rates and durable symptom control. However, its limitations—such as cytopenias, infectious complications, and incomplete responses—have catalyzed the development of next-generation agents. In 2024, the FDA approved axatilimab, a CSF-1R inhibitor that targets monocyte-derived macrophages in fibrotic chronic GVHD, and remestemcel-L, an allogeneic mesenchymal stromal cell therapy, for pediatric steroid-refractory acute GVHD. Both agents offer mechanistically distinct and clinically meaningful additions to the therapeutic armamentarium. In parallel, emerging combination strategies involving JAK2 inhibitors and novel biologics show promise in enhancing immune tolerance while preserving graft-versus-leukemia (GvL) effects. Recent advances in biomarker development, such as the MAGIC Algorithm Probability (MAP), are enabling early risk stratification and response prediction. The integration of these tools with organ-specific and personalized approaches marks a shift toward more precise, durable, and tolerable GVHD therapy. This review highlights the current state and future direction of JAK2 inhibition and complementary therapies in the evolving GVHD treatment paradigm. Full article

Wound healing remains a significant hurdle within the field of medical practice, especially concerning chronic and non-healing injuries. Conventional interventions, such as skin grafts, wound dressings, and biomaterials, offer structural support for the regenerated tissues but often lack the biological signaling cues essential for tissue regeneration. However, these approaches often lack the biological signals necessary to promote effective tissue repair. An emerging strategy involves incorporating cell-secreted proteins, known as the secretome, into biomaterials. The secretome contains bioactive elements such as cytokines, growth factors, and extracellular vesicles (EVs), which enhance the wound healing process. This review explores the potential of secretome-loaded biomaterials in modulating inflammation, promoting angiogenesis, and assisting in the remodeling of the extracellular matrix (ECM). Recent advancements in biomaterial engineering technology, such as 3-dimensional (3D) bioprinting, have improved the controlled delivery and bioactivity of secretome at the wound site. These gel-based biomaterials enhance wound healing by providing sustained bioactive molecule release, improving cell growth, and tissue repair. Despite these promising outcomes, limitations including variations in secretome composition and difficulties in large-scale production. Hence, secretome-loaded biomaterials offer a promising solution for wound healing, but further research is needed to optimize formulations, ensure stability, and validate clinical applications. Full article

A platform of two-component cross-linked hydrogel (cGEL) based on gelatinous peptides and anhydride-containing cross-linkers (oPNMA, oPDMA) is extended for use in peripheral nerve regeneration. Hybrid composites with bio-/chemical cues for enhanced biophysical and biochemical properties were fabricated by covalently grafting small molecular, heterobifunctional amines including the nerve growth factor mimetic LM11A-31 to the oligomeric cross-linkers prior to hydrogel formation. The cytocompatibility and growth-supportive conditions within the matrix are confirmed for pristine and modified hydrogels using L929 mouse fibroblasts and human adipose-derived stem cells (hASCs). For hASCs, cell behavior depends on the type of cross-linker and integrated amine. In a subsequent step, neonatal rat Schwann cells (SCs) are seeded on pristine and functionalized cGEL to investigate the materials’ capabilities to support SC growth and morphology. Within all formulations, cell viability, adherence, and cell extension are maintained though the cell elongation and orientation vary compared to the two-dimensional control. It is possible to merge adjustable two-component hydrogels with amines as biochemical signals, leading to improved nervous cell proliferation and activity. This indicates the potential of tunable bioactive cGEL as biomaterials in nerve implants, suggesting their use as a foundational component for nerve conduits. Full article

This study developed electrosprayed deferoxamine (DFO)-loaded poly(lactic-co-glycolic acid) microspheres (DFO-MS) combined with a sucrose acetate isobutyrate (SAIB) depot (DFO-MS@SAIB) for bone-defect repair, targeting the coordinated regulation of angiogenesis and osteogenesis in vascularized bone regeneration—where new blood vessels support functional bone integration. In vitro/in vivo evaluations confirmed its dual pro-angiogenic and pro-osteogenic effects via HIF-1α pathway activation. Background/Objectives: Emerging evidence underscores the indispensability of vascularization in bone-defect repair, a clinical challenge exacerbated by limited intrinsic healing capacity. While autologous grafts and growth-factor-based strategies remain mainstream, their utility is constrained by donor-site morbidity, transient bioactivity, and poor spatiotemporal control over angiogenic–osteogenic coupling. Here, we leveraged DFO, a hypoxia-mimetic HIF-1α stabilizer with angiogenic potential, to engineer an injectable DFO-MS@SAIB depot. This system was designed to achieve sustained DFO release, thereby synchronizing vascular network formation with mineralized tissue regeneration in critical-sized defects. Methods: DFO-MS were fabricated via electrospraying and combined with SAIB (DFO-MS@S) to form an injectable sustained-release depot. Their physicochemical properties, including morphology, encapsulation efficiency, degradation, release kinetics, and rheology, were systematically characterized. In vitro, the angiogenic capacity of HUVECs co-cultured with DFO-MS was evaluated; conditioned HUVECs were then co-cultured with BMSCs to assess the BMSCs’ cytocompatibility and osteogenic differentiation. In vivo bone regeneration in a rat calvarial defect model was evaluated using micro-CT, histology, and immunohistochemistry. Results: The DFO-MS@SAIB system achieved sustained DFO release, stimulating HUVEC proliferation, migration, and tubulogenesis. In a Transwell co-culture model, pretreated HUVECs promoted BMSC migration and osteogenic differentiation via paracrine signaling involving endothelial-secreted factors (e.g., VEGF). HIF-1α pathway activation upregulated osteogenic markers (ALP, Col1a1, OCN), while in vivo experiments demonstrated enhanced vascularized bone regeneration, with significantly increased bone volume/total volume (BV/TV) and new bone area compared with controls. Conclusion: The DFO-MS@SAIB system promotes bone regeneration via sustained deferoxamine release and HIF-1α-mediated signaling. Its angiogenesis–osteogenesis coupling effect facilitates vascularized bone regeneration, thereby offering a translatable strategy for critical-sized bone-defect repair. Full article

Tissue substitution and graft transplantation are currently the best treatment options for patients suffering from severe heart diseases. However, the limited availability of donors and the restricted durability of tissues applied in cardiovascular treatments result in a constraint on applicability and a suboptimal therapeutic approach that is still not fully resolved. There are multiple ways to preserve heart tissue grafts, and the choice of method is solely dependent upon the nature and complexity of the tissue and the length of storage. The conventional cold storage method provides the base to nearly all of the preservation protocols for short- and long-term storage. Short-term storage methods frequently rely on designing preserving solutions to protect the graft against warm and cold ischemia at the temperature above freezing point. As ice-nucleation is the major notorious phenomenon during graft preservation, the modern era of research is focusing on developing ice-free preservation techniques, termed vitrification. However, despite the promising outcomes of vitrification, there are several recognized hurdles required to be overcome to build a biobank of heart grafts for an extended period of time. Besides tissue deterioration due to extreme cold temperature, there is another extreme phenomenon of tissue rejection mainly caused by the presence of cellular antigens. The modern approach of decellularization has the potential to minimize the chances of tissue rejection by removing the cells and providing a structural support and sustained biochemical signal via keeping the extracellular matrix of the graft intact. In conclusion, both nano-warming and decellularization are the leading approaches that have great potential to store the graft tissue in its optimal form via keeping its viability safe for a longer time and extending its applicability. This review article outlines a variety of approaches for the preservation and bioengineering of tissue to fulfill the need for the availability of on-shelf long-lasting grafts both in clinical and laboratory setups. Full article

A 75-year-old man, with a history of descending thoracic aortic rupture and dissection treated with aortic stenting at 73 years old, was admitted for rehabilitation following recurrent cerebral ischemic attacks. Upon admission, blood tests revealed elevated inflammatory markers, including a C-reactive protein (CRP) level of 10.75 mg/dL and a D-dimer level of 4.2 µg/mL, alongside microcytic anemia. Despite thorough evaluations using computed tomography (CT) and ultrasound, the origin of these abnormalities remained unidentified. Two months later, MRI using diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) revealed hyperintensities in the thoracic aorta. He remained asymptomatic and progressed well during rehabilitation, prompting continued observation. However, three months after admission, he developed hemoptysis. Contrast-enhanced CT showed pneumonia, as well as enhanced lesions in the aortic wall, confirming aortic inflammation. Due to concerns about aortic stent ulceration, an emergency stent graft insertion extending to the superior mesenteric artery was performed. He recovered uneventfully and was discharged. DWIBS is an MRI-based tool that avoids exposure to radiation or contrast agents and is cost-effective. MRI using DWIBS demonstrated high signal accumulations in the aortic wall, indicative of inflammation. These findings suggest that DWIBS holds significant potential as a powerful imaging tool for detecting and assessing inflammation, particularly in the aorta. Full article

Grafting is a prevalent horticultural technique that enhances crop yields and stress resilience; nevertheless, compatibility issues frequently constrain its efficacy. This research examined the physiological, hormonal, and transcriptional factors regulating compatibility between the litchi (Litchi chinensis Sonn.) cultivars Feizixiao (FZX) and Ziniangxi (ZNX). The anatomical and growth investigations demonstrated significant disparities between compatible (FZX as scion and ZNX as rootstock) and incompatible (ZNX as scion and FZX as rootstock) grafts, with the latter showing reduced levels of indole acetic acid (IAA). Exogenous 1-naphthalene acetic acid (NAA) application markedly improved the graft survival, shoot development, and hormonal synergy, whereas the auxin inhibitor tri-iodobenzoic acid (TIBA) diminished these parameters. The incompatible grafts showed downregulation of auxin transporter genes, including ATP-binding cassette (ABC) transporter, AUXIN1/LIKE AUX1 (AUX/LAX), and PIN-FORMED (PIN) genes, suggesting impaired vascular tissue growth. Metabolomic profiling revealed dynamic interactions between auxin, salicylic acid, and jasmonic acid, with NAA-treated grafts exhibiting enhanced levels of stress-responsive metabolites. Transcriptome sequencing identified differentially expressed genes (DEGs) linked to auxin signaling (ARF, GH3), seven additional phytohormones, secondary metabolism (terpenoids, anthocyanins, and phenylpropanoids), and ABC transporters. Gene ontology and KEGG analyses highlighted the significance of hormone interactions and the biosynthesis of secondary metabolites in successful grafting. qRT-PCR validation substantiated the veracity of the transcriptome data, emphasizing the significance of auxin transport and signaling in effective graft development. This study provides an in-depth review of the molecular and physiological factors influencing litchi grafting. These findings provide critical insights for enhancing graft success rates in agricultural operations via targeted hormonal and genetic approaches. Full article

This study reports the synthesis and characterization of a novel carboxymethyl cellulose–N-fullerene–g-poly(co-acrylamido-2-methyl-1-propane sulfonic acid) (CMC–N-fullerene–AMPS) hydrogel for potential application in biosensing within food packaging. The hydrogel was synthesized via free radical polymerization and characterized using FTIR, SEM, and fluorescence microscopy. FTIR analysis confirmed the successful grafting of AMPS and incorporation of N-fullerenes, indicated by characteristic peaks and a shift in the N–H/O–H stretching frequency. Density Functional Theory (DFT) calculations revealed that the CMC–N-fullerene–AMPS hydrogel exhibited higher stability and a lower band gap energy (0.0871 eV) compared to the CMC–AMPS hydrogel, which means a high reactivity of CMC–N-fullerene–AMPS. The incorporation of N-fullerenes significantly enhanced the hydrogel’s antibacterial activity, demonstrating a 22 mm inhibition zone against E. coli and a 24 mm zone against S. aureus, suggesting potential for active food packaging applications. Critically, the hydrogel displayed a unique “turn-on” fluorescence response in the presence of bacteria, with distinct color changes observed upon interaction with E. coli (orange-red) and S. aureus (bright green). This fluorescence enhancement, coupled with the porous morphology observed via SEM (pore size 377–931 µm), suggests the potential of this hydrogel as a sensing platform for bacterial contamination within food packaging. These combined properties of enhanced antibacterial activity and a distinct, bacteria-induced fluorescence signal make the CMC–N-fullerene–AMPS hydrogel a promising candidate for developing intelligent food packaging materials capable of detecting bacterial spoilage. Full article