Search Results (236)

Background and Clinical Significance: Cardiac and mediastinal angiosarcomas are rare, aggressive malignancies that often present with nonspecific symptoms and pose significant diagnostic challenges. Tumor heterogeneity and necrosis may lead to false-negative biopsy results; Case Presentation: We report a 64-year-old man who initially presented with cardiac tamponade of unclear etiology. Despite an extensive workup, the patient remained asymptomatic for five months before re-presenting with dyspnea and a large mediastinal mass compressing the right heart, along with a lytic rib lesion. Initial ultrasound-guided biopsy of the rib lesion demonstrated a benign vascular proliferation consistent with Masson tumor (intravascular papillary endothelial hyperplasia), which was discordant with aggressive imaging findings. Further evaluation with positron emission tomography–computed tomography (PET-CT) revealed peripheral metabolic activity, and cardiac magnetic resonance imaging (MRI) demonstrated a heterogeneous mass with central necrosis and peripheral enhancement. A repeat CT-guided biopsy targeting the metabolically active region confirmed angiosarcoma, with immunohistochemical staining demonstrating diffuse positivity for ERG, CD31, and CD34. The patient was treated with palliative radiation and paclitaxel-based chemotherapy but experienced rapid clinical decline and transitioned to comfort-focused care; Conclusions: This case highlights the importance of correlating imaging with pathology and emphasizes the risk of sampling error in necrotic tumors. PET-guided biopsy targeting viable tumor regions is essential in cases with discordant findings. Full article

Background/Objectives: An ideal bone scaffold should promote bone cell growth and functional vascularization, hence the importance of imbuing biomaterials with pro-angiogenic cues. In this work, silica-based bioactive glasses, either pristine (SBA3) or doped with copper (SBA3_Cu), were embedded in poly(ε-caprolactone) (PCL), which was also used as a control. Methods: In vitro co-cultures of adipose-derived mesenchymal stem/stromal cells (ASCs) and human microvascular endothelial cells (HMEC-1s) were kept in α-MEM, MCDB131, and EndoGRO media to test the biomaterials. The co-cultures were visualized by immunofluorescence and SEM, while flow cytometry was performed to characterize cellular immunophenotype. The angiogenic potential was evaluated using conditioned media of co-cultures to perform a tubulogenesis assay and VEGF-A quantification. Results: Immunophenotypic analysis showed a significant decrease in the endothelial CD31+ cellular subset, whereas the OB-like cellular subset expressing CD105, CD73, CD90, and ALP increased in all culture media over time. In α-MEM, HMEC-1s were unable to form a capillary network independent of the substrates. A more organized network was visible when co-cultures were plated on PCL, in MCDB131 and EndoGRO, or if they were kept in EndoGRO on PCL/SBA3_Cu. The VEGF-A concentrations were similar in the conditioned media from co-cultures grown on PCL/SBA_Cu, in EndoGRO, and on PCL and PCL/SBA3, in MCDB131. Conclusions: The presence of copper did not promote the angiogenic potential of HMEC-1, likely due to the low concentration of released copper ions and the predominant osteoinductive effect of the other ions released by the bioglass. A re-evaluation of formulation and structure of bioglass scaffold could enhance the angiogenic potential. Full article

Background: Diabetic macular edema (DME) is a leading cause of vision loss. Although real-world data on faricimab, a bispecific antibody targeting vascular endothelial growth factor-A and Angiopoietin-2, are expanding, its long-term durability in routine clinical practice has not yet been fully established. We evaluated effectiveness, anatomic response and treatment durability of first-line faricimab in treatment-naïve DME. Methods: We conducted a single-center, retrospective cohort study of treatment-naïve DME eyes initiated on intravitreal faricimab (August 2023–October 2024) in a real-world setting. After a loading phase, eyes were managed with a treat-and-extend or pro re nata regimen. The primary endpoint was retreatment interval at 48 weeks. Secondary endpoints were retreatment interval at weeks 12, 24 and 36; change in visual acuity (VA); central subfield thickness (CST); and optical coherence tomography (OCT) fluid. Results: Fifty-two eyes from 40 consecutive patients were included (baseline VA 65.96 ± 13.55 letters; CST 426.56 ± 106.72 µm). Mean injections were 4.02 ± 1.11 between months 1–6 and 1.90 ± 0.98 between months 7–12. VA improved by +8.46, +7.57, +7.65 and +7.72 letters at 12, 24, 36, and 48 weeks (all p < 0.0001), respectively. Relative CST decreased by −28.05%, −27.01%, −29.46% and −25.22% at the same time points (all p < 0.0001). At week 48, 15.4% of eyes were on a treatment interval of less than 12 weeks, 23.1% were between 12 and 16 weeks, and 46.1% were on 16 or more weeks; 15.4% were managed PRN. Conclusions: First-line faricimab in treatment-naïve DME in a real-world setting yielded clinically meaningful and durable extensions in treatment intervals, alongside sustained functional and anatomical improvements. Full article

Skin wound healing is a complex and highly coordinated biological process involving inflammation, cell migration and proliferation, angiogenesis, extracellular matrix remodeling and tissue regeneration. While the zebrafish-derived antimicrobial peptide AP10W exhibits broad-spectrum antimicrobial properties, its potential in tissue repair remains unexplored. Herein, we demonstrate that AP10W possesses intrinsic wound-healing capabilities, providing a preliminary investigation into its underlying mechanisms. In this study, using a full-thickness murine wound model and in vitro cell-based assays to evaluate the effects of AP10W on fibroblasts, keratinocytes, endothelial cells, and macrophages, we found that AP10W significantly promoted fibroblast and keratinocyte migration and proliferation. Furthermore, it enhanced endothelial cell motility, survival, and tube formation, while upregulating key pro-angiogenic factors, including Vascular endothelial growth factor A (VEGFA), Platelet-derived growth factor (PDGF), and Fibroblast growth factor 2 (FGF2). Concurrently, AP10W drove macrophage reprogramming from a pro-inflammatory M1 phenotype toward a pro-healing M2 state, as evidenced by upregulated Arginase-1 (Arg-1) and Interleukin-10 (Il-10) expression, alongside attenuated Tumor necrosis factor-alpha (Tnf-α), Interleukin-1 beta (Il-1β), Interleukin-6 (Il-6), and Inducible nitric oxide synthase (iNOS) levels. In vivo, the topical application of AP10W accelerated wound closure, markedly improving re-epithelialization, collagen deposition, vascularization, tissue perfusion, and skin appendage regeneration. Preliminary mechanistic studies revealed that AP10W increased YAP expression and nuclear translocation; conversely, the pharmacological inhibition of YAP significantly abrogated these pro-healing effects. Collectively, our findings identify AP10W as a multifunctional peptide with potent wound-healing properties, positioning it as a promising candidate for wound therapy. Full article

Background: Impaired angiogenesis and persistent inflammation are hallmarks of chronic diabetic wounds. Extracellular vesicles derived from dental pulp stem cells (DPSC-EVs) represent a promising cell-free therapy for tissue repair; however, their clinical translation is hindered by suboptimal yields and attenuated bioactivity associated with conventional two-dimensional (2D) culture. This study investigated whether a biomimetic three-dimensional (3D) fibrin/gelatin hydrogel system could optimize the therapeutic potency of DPSC-EVs for diabetic wound healing. Methods: DPSCs were encapsulated within 3D fibrin/gelatin scaffolds, followed by comprehensive characterization of cell viability and morphology. 3D-EVs and 2D-EVs were isolated via ultracentrifugation and validated by transmission electron microscopy and nanoparticle tracking analysis. The pro-angiogenic capacity of 3D-EVs was evaluated using human umbilical vein endothelial cells (HUVECs) under high-glucose (HG) stress. Additionally, the immunomodulatory effects were assessed by monitoring macrophage polarization in lipopolysaccharide-stimulated RAW 264.7 cells. The therapeutic efficacy was further validated in vivo using a streptozotocin (STZ)-induced diabetic mouse model with full-thickness cutaneous wounds. Results: The 3D fibrin/gelatin hydrogel provided a supportive microenvironment that significantly augmented the secretory productivity of DPSCs. Compared to 2D-EVs, 3D-EVs exhibited superior functional resilience in restoring HUVEC migration and tube formation under HG-induced oxidative stress. Furthermore, 3D-EVs effectively orchestrated the macrophage transition from a pro-inflammatory M1 phenotype toward an anti-inflammatory M2 phenotype, thereby modulating the immune microenvironment. In vivo, topical administration of 3D-EVs markedly accelerated wound closure, promoted re-epithelialization, and enhanced microvascular density and collagen maturation in diabetic mice. Conclusions: Our findings demonstrate that the 3D fibrin/gelatin culture system effectively primes the therapeutic profile of DPSC-EVs. These engineered vesicles accelerate diabetic wound healing by synergistically promoting angiogenesis and resolving chronic inflammation, offering a robust and potent cell-free strategy for the management of chronic diabetic ulcers. Full article

Objectives: Seawater-immersed burn wounds are highly susceptible to contamination, persistent inflammation, oxidative stress, and delayed healing, while current irrigation solutions remain suboptimal for such acute injuries. This study aimed to evaluate the therapeutic efficacy and underlying mechanisms of plasma-activated water (PAW) as a novel irrigation strategy for these complex wounds. Methods: The antibacterial efficacy of PAW against marine pathogens was first evaluated in vitro. Subsequently, a rat model of seawater-immersed burn injury was established in male Sprague-Dawley (SD) rats to assess the therapeutic effects of PAW irrigation on wound healing, infection control, and underlying biological mechanisms. Results: In vitro, PAW significantly eradicated two major marine pathogens, Vibrio vulnificus and Vibrio parahaemolyticus (p < 0.001). In vivo, PAW markedly accelerated wound closure, achieving complete healing in 23.60 ± 6.50 days vs. 38.67 ± 2.08 days (Normal saline group) and 58.33 ± 10.97 days (Model group) (p < 0.05). PAW significantly reduced bacterial burden, modulated inflammation by decreasing interleukin-6 and increasing interleukin-10, and alleviated oxidative stress, as evidenced by reduced malondialdehyde levels and enhanced superoxide dismutase activity. Histological evaluation demonstrated enhanced re-epithelialization, collagen deposition, and increased expression of vascular endothelial growth factor and platelet endothelial cell adhesion molecule-1. No adverse effects on serum biochemistry or major organ histopathology were observed. Conclusions: PAW may be a safe, promising, and multifunctional irrigation strategy that promotes seawater-immersed burn healing through coordinated antibacterial, anti-inflammatory, antioxidant, and pro-angiogenic effects, highlighting its strong potential for clinical translation. Full article

Mussel foot proteins (Mfps) are renowned for their underwater adhesion, whereas their biotechnological potential for cutaneous wound repair remains largely underexplored. In this study, we identified and characterized a cysteine-rich mussel foot protein, Mfp6-1, from Mytilus coruscus and investigated its therapeutic potential for wound healing. Sequence analysis showed that Mfp6-1 is enriched in cysteine (11.0%) and tyrosine (~16.5%). We successfully expressed recombinant Mfp6-1 (rMfp6-1) in E. coli. Structural prediction based on the mature peptide sequence suggested that rMfp6-1 adopts a relatively compact fold containing several short β-structural elements. In vitro assays demonstrated that rMfp6-1 possesses antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and alkylation experiments suggested that cysteine residues contribute importantly to this activity. Dithio-bis-nitrobenzoic acid (DTNB)-based thiol quantification further demonstrated that rMfp6-1 contained abundant accessible free sulfhydryl groups, supporting an important contribution of cysteine-derived thiols to its antioxidant activity. Experiments on a full-thickness mouse wound model showed that rMfp6-1 treatment resulted in significantly faster wound contraction. Morphological analysis further revealed that rMfp6-1 optimizes the healing microenvironment by promoting collagen accumulation and re-epithelialization. Additionally, the treatment was found to trigger vascular endothelial growth factor (VEGF)-mediated angiogenesis, thereby improving the overall quality of the regenerated tissue. Furthermore, rMfp6-1 treatment significantly reduced interleukin-6 (IL-6) expression, suggesting that its antioxidant capacity creates a permissive microenvironment for tissue regeneration by suppressing excessive inflammation. These findings indicate that recombinant rMfp6-1 is a promising bioactive candidate for wound-healing applications. Full article

Diabetic wounds are a common and severe complication of diabetes mellitus, characterized by delayed healing due to persistent inflammation, impaired angiogenesis, and cellular dysfunction. Conventional therapeutic approaches remain limited in efficacy. In recent years, exosomes have attracted considerable attention in wound healing and regenerative medicine because of their crucial role in intercellular communication and tissue repair. However, rapid clearance of exosomes in vivo greatly limits their therapeutic efficacy. To address this critical limitation, we engineered a decellularized extracellular matrix (dECM)-based hydrogel system functionalized with exosomes derived from skin-derived precursor cells (SKPs). This biomimetic scaffold was designed to serve as a local exosome-delivery platform at the wound site, with the aim of improving exosome utilization and augmenting their regenerative effects. Comprehensive in vitro characterization demonstrated that the exosome-loaded composite hydrogels exhibited robust pro-angiogenic activity, as evidenced by enhanced endothelial cell proliferation, migration, and tube formation. Moreover, the hydrogels displayed significant antibacterial effects against wound-relevant pathogens and potent reactive oxygen species (ROS)-scavenging capacity, thereby mitigating oxidative damage. Notably, the composite hydrogels also promoted the phenotypic polarization of macrophages toward the pro-regenerative M2 phenotype. In parallel, in vivo studies using a streptozotocin-induced diabetic rat wound model confirmed that treatment with the composite hydrogels significantly accelerated wound closure rates compared to control groups. Histological and immunohistochemical analyses revealed enhanced angiogenesis, as evidenced by increased CD31-positive microvessel density, as well as improved collagen deposition, re-epithelialization, and an attenuated local inflammatory microenvironment characterized by reduced pro-inflammatory cytokine expression and elevated M2 macrophage infiltration. Collectively, the SKPs exosome-loaded dECM based composite hydrogels developed in this study represent a potential therapeutic strategy for the treatment of diabetic wounds. Full article

Descemet stripping automated endothelial keratoplasty (DSAEK) is a well-established surgical technique for the treatment of endothelial dysfunction, in which intracameral gas tamponade plays a critical role in graft adherence. We report the case of a 67-year-old pseudophakic woman with advanced Fuchs endothelial corneal dystrophy and symptomatic pseudophakic bullous keratopathy in the right eye, who presented with progressive visual deterioration and underwent DSAEK using an 8.25 mm donor graft inserted with a Busin glide and tamponaded with a 25% sulfur hexafluoride (SF6) gas–air mixture. On the first postoperative day, slit-lamp examination suggested an appropriate anterior chamber configuration and satisfactory graft attachment. However, detailed multiplanar anterior segment optical coherence tomography (AS-OCT), defined here as assessment using vertical, horizontal, and rotational scan orientations, revealed subtle posterior migration of the gas bubble beneath the iris plane. This clinically occult finding indicated altered anterior segment anatomy associated with a risk of secondary angle-closure mechanisms and raised concern for malignant glaucoma. Prompt surgical re-intervention was undertaken on postoperative day one, involving decompression of the misdirected gas bubble and reinjection of a centrally positioned tamponade. This resulted in restoration of normal anterior chamber configuration and stable graft adherence. Best-corrected visual acuity (BCVA) improved from 0.1 Snellen (1.0 logMAR) preoperatively to 0.7 Snellen (0.15 logMAR) at 2 weeks following surgery. This case highlights the added value of multiplanar AS-OCT in detecting clinically occult posterior gas migration after DSAEK, particularly when the abnormality is scan-orientation-dependent and not apparent on slit-lamp examination, thereby enabling timely intervention in the presence of a potentially sight-threatening postoperative configuration. Full article

Pulmonary bioengineering holds significant promise for the development of functional lungs suitable for transplantation in patients with terminal lung diseases; however, it encounters considerable challenges. The inherent structural complexity, diverse cellular composition, and the intricate process of re-endothelialization the pulmonary vasculature complicate efforts to reconstruct viable lungs for transplantation. This study aimed to establish an innovative re-endothelialization technique utilizing decellularized scaffolds, integrating canine yolk sac-derived endothelial precursor cells with mechanical respiratory stimuli within a bioreactor framework. Wistar rat lungs were subjected to a decellularization protocol employing SDS + Triton X-100 0.5% and subsequently assessed for cytocompatibility with murine fibroblasts (3T3) and yolk sac (YS) cells in fragments. Following this, the recellularization of the whole-lung scaffold was evaluated under constant mechanical respiratory stimulation with YS cells. Each stage of the process was rigorously analyzed using histological staining, DAPI, scanning electron microscopy (SEM), and genomic DNA quantification. The findings reveal that the implemented alternating decellularization protocol resulted in a structured scaffold conducive to the culture of various cell types in fragments. When subjected to the complete scaffold recellularization model, the results indicated that YS cells are advantageous for the re-endothelialization process. Moreover, when employed in conjunction with the bioreactor model incorporating respiratory stimulation, these cells demonstrated enhanced cellular diffusion capacity and facilitated more homogeneous recellularization of the entire organ. These results signify a notable advancement in the reconstruction of new tissues for pulmonary transplantation. Full article

Marine red algae have been reported to contain a variety of bioactive compounds that are effective in promoting wound-healing processes. In the present study, the wound-healing potential of Grateloupia angusta, which has been rarely explored, was examined using in vitro and in vivo models. A 70% ethanol extract of G. angusta (GAE) was prepared and profiled by liquid chromatography–mass spectrometry (LC-MS). Its effects on the wound-healing process were examined using three different types of cells that participate in this process, namely, Raw264.7, human umbilical vein endothelial cells (HUVECs), and human dermal fibroblasts (HDFs). Various assays including migration/scratch, tube formation, procollagen type I C-peptide production, and Western blotting were used to investigate the therapeutic potential of GAE. In vivo efficacy was tested in a mouse full-thickness skin incision wound model. In HUVECs, GAE increased viability, migration, tube formation, and vascular endothelial growth factor (VEGF) expression. Raw264.7 cells also showed increased VEGF production following GAE treatment. In HDFs, GAE did not affect proliferation and migration, but did increase collagen production. In mice, GAE accelerated wound closure from day 3 to day 5 and increased granulation/matrix with higher proliferating cell nuclear antigen (PCNA) and cluster of differentiation 31 (CD31) expression after a single topical application. In addition, keratin 14 (K14) expression was restored in GAE-treated wound tissues, suggesting improved epidermal re-epithelialization. Taken together, GAE promotes matrix production and pro-angiogenic activity in vitro and improves early wound repair in vivo, suggesting that G. angusta is a promising marine-derived candidate for wound-healing adjuvants. The results of the present study support further bioassay-guided fractionation and mechanistic validation in future studies. Full article

Background: Diabetic wounds represent a major clinical challenge due to persistent inflammation, oxidative stress, and impaired angiogenesis. Bone marrow mesenchymal stem cells (BMSCs) have strong regenerative potential, and their therapeutic effects and optimization strategies for diabetic wounds warrant further exploration. Objective: This study aimed to improve the therapeutic efficacy of BMSCs in diabetic wound healing via chrysin pretreatment, as well as to evaluate the healing capacity and molecular mechanisms of the derived chrysin-pretreated BMSC-conditioned medium (Chrysin-CM). Methods: BMSCs were pretreated with 1 μM chrysin for 48 h to generate Chrysin-CM. The therapeutic effects were evaluated in vitro by analyzing the proliferation, migration, and matrix synthesis of human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs) under high-glucose (HG) conditions. In vivo, a diabetic mouse model with full-thickness excisional wounds was established and treated topically with Chrysin-CM. Transcriptomic sequencing and immune infiltration analysis of wound tissues were performed on day 14 in order to investigate the underlying mechanisms. Results: Chrysin pretreatment significantly enhanced the functional activity of BMSCs, accompanied by increased proliferative capacity and accelerated cell cycle progression. In vitro, Chrysin-CM demonstrated superior efficacy, robustly protecting HUVECs and HSFs from HG-induced dysfunction. In vivo, Chrysin-CM significantly accelerated wound closure, re-epithelialization, and neovascularization compared to the control. Mechanistically, RNA sequencing (RNA-seq) revealed that Chrysin-CM induced multi-level remodeling, characterized by reduced inflammatory gene expression and immune cell infiltration, along with the upregulation of regenerative genes and alternative splicing events. Conclusions: Chrysin successfully improved the therapeutic efficacy of the BMSC secretome in wound healing. Chrysin-CM effectively accelerated diabetic wound healing by actively resolving chronic inflammation and promoting angiogenesis and structural remodeling, thus providing a potential strategy for stem cell-based cell-free treatment for chronic diabetic wounds. Full article

The endothelial protein C receptor (EPCR) is an important component of the protein C (PC) system, recognised for its diverse roles in blood coagulation, inflammation, and stem cell regulation. Wound healing is a complex physiological process that can be divided into four distinct but overlapping phases: haemostasis, inflammation, proliferation and remodelling. Recently, EPCR has emerged as a key regulator in wound repair and regeneration. During haemostasis, EPCR enhances the conversion of PC to its activated form (APC) to optimise local and systemic anticoagulation. In the inflammatory phase, EPCR modulates immune cell activity, inhibits inflammatory factors, and maintains tissue barrier integrity. As the process transitions to the proliferative phase, EPCR promotes endothelial and epithelial cell proliferation, migration, neovascularisation and re-epithelization, and mediates the expression of matrix metalloproteinases to facilitate tissue reconstruction. Finally, during the remodelling phase, EPCR exerts a potential antifibrotic effect by regulating fibroblast activation and collagen deposition via the Transforming growth factor (TGF)-β1/Smad3 pathway, ensuring functional repair. While therapeutic potential has been shown in animal models, translating EPCR-mediated therapies to clinical application faces many challenges, including wound heterogeneity, dosage control, targeted delivery, and potential bleeding risks. Studies have shown that local drug delivery strategies, non-anticoagulant APC variants, and individualised treatment based on EPCR expression will be the key directions for future development. Additionally, EPCR may serve as a potential biomarker for assessing wound severity and guiding personalised interventions. Full article

Infectious diseases remain a major cause of mortality and disability worldwide. This burden is driven, in part, by antimicrobial resistance (AMR) and the re-emergence of epidemic and pandemic threats, underscoring the need for translational research to address knowledge gaps exposed by recent pandemics. Despite significant advances enabled by antibiotics and antivirals, their effectiveness is increasingly constrained by resistance development, limited pathogen spectra, and prolonged development timelines that fail to keep pace with rapidly shifting epidemiology. Diagnostic limitations impede timely pathogen identification and hinder the development of treatment regimens informed by pathogen mechanisms of action. Severe infections frequently involve dysregulated host responses, including hyperinflammation, inflammasome activation, and endothelial or immunothrombotic injury, which may progress to sepsis, immunoparalysis, or chronic sequelae, highlighting the limitations of pathogen-centered paradigms. Conventional biomarkers and culture-based microbiology are often slow or nonspecific, while molecular assays may not reliably distinguish colonization from active infection or capture host-response heterogeneity shaped by age, immune competence, and disease stage. This review synthesizes mechanistic and translational insights across three interrelated axes: (i) host–pathogen interactions, with a focus on innate immune sensing networks (e.g., Toll-like receptors, inflammasomes, RIG-I-like receptors, and cGAS-STING) and microbial replication and immune evasion strategies; (ii) clinical and public health implications, spanning acute organ dysfunction syndromes, post-acute infection syndromes, and AMR-driven health system strain; and (iii) emerging therapeutics along a continuum of pathogen-, virulence-, host-, and immune-directed approaches. Emphasis is placed on anti-virulence therapeutics, bacteriophage therapy, monoclonal antibodies, and engineered immune modalities within frameworks of quantitative translational pharmacology and implementation science. Finally, an integrative conceptual framework encompassing mechanistic phenotypes, host-response diagnostics, and stage-adapted therapeutic combinations is proposed to guide rational intervention across endemic infections and future pandemic preparedness. Full article

Flap reconstruction remains a cornerstone after oncologic resection, trauma, and complex wounds, yet partial necrosis, venous congestion, and delayed healing continue to drive morbidity and unplanned re-exploration. Even when macroscopic inflow and outflow are re-established, distal and border-zone tissue may remain constrained by microcirculatory dysfunction. This review frames flap compromise as a biomimetics-relevant failure of a hierarchical transport network and summarizes the vascular repair mechanisms that regenerative interventions aim to replicate. We outline key concepts governing flap perfusion, including angiosomes, choke vessels, endothelial barrier failure, mural cell support, and immune regulation within the angiogenic niche, and relate these to no-reflow, thrombo-inflammation, and impaired vascular regeneration. We then synthesize regenerative strategies aimed at durable reperfusion, spanning recombinant factors, gene and nucleic acid delivery, cell-based therapies, cell-free biologics, including extracellular vesicles and platelet-derived products, pharmacologic modulators, and biomaterial platforms that localize and sustain bioactivity. Translation will require functional perfusion endpoints, standardized reporting of delivery parameters, and safety-conscious designs that minimize aberrant angiogenesis and vector-related risks in post-resection settings. Full article