Search Results (240)

Background: Platelet-rich plasma (PRP) plays a crucial role in chronic wound healing by releasing growth factors that regulate inflammation, promote angiogenesis, and stimulate tissue regeneration. Methods and Results: Here, an animal source of PRP, named ApiRegenin and derived from cultivated deer blood, was established. Specific protein and non-protein biomarkers—including nicotinamide, palmitic acid, IGF, and fibronectin—were validated to ensure batch-to-batch quality control. The pharmacological properties of ApiRegenin in cultured cells transfected with DNA encoding HRE and NF-κB reporter constructs were validated, serving as a functional control. In a skin-defective model of db/db diabetic mice, accelerated wound healing was observed following ApiRegenin treatment. Histological analysis revealed enhancements of re-epithelialization, granulation tissue formation, and collagen deposition. In parallel, the immunofluorescence staining of CD31, α-SMA, and VEGF was upregulated, indicating the promotion of angiogenesis. Furthermore, ApiRegenin treatment shifted the local immune microenvironment toward an M2-like macrophage phenotype, characterized by the downregulation of iNOS and the contrastive upregulation of Arg-1. At the molecular level, transcriptomic enrichment analysis suggested the prominent involvement of the HIF-1, PI3K-Akt, and TNF signaling pathways. Conclusions: These findings demonstrate that ApiRegenin effectively accelerates diabetic wound healing by promoting angiogenesis and modulating macrophage polarization. Full article

Chronic wounds are associated with long-standing inflammation, impaired angiogenesis, oxidative stress, microbial load and defective remodelling of the extracellular matrix, impairing tissue repair. Conventional dressings offer protection and moisture regulation but do not sufficiently address the biological failures. Electrospun nanofibrous wound dressings offer a more active regenerative platform due to their architecture, which resembles the extracellular matrix, allowing cell adhesion and migration and facilitating the localised delivery of therapeutic agents. Marine-derived polysaccharides, such as alginate, chitosan, carrageenan, fucoidan, glycosaminoglycans, and ulvan, are particularly attractive in this area due to their biocompatibility, biodegradability, sustainability, and intrinsic haemostatic, antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory properties. This review critically discusses the mechanistic and translational relevance of marine polysaccharide-based nanofibres in wound healing with a focus on inflammation resolution, polarisation of macrophages, responses of keratinocytes and fibroblasts, angiogenesis, collagen deposition, redox balance and matrix remodelling. Biofabrication strategies, especially electrospinning and related nanofibre-forming strategies, are reviewed from the aspects of scaffold architecture, drug-loading capacity, controlled release, and wound microenvironment modulation. The review also discusses current shortcomings such as heterogeneity in the composition of marine polymers, mechanical fragility, sterilisation and storage issues, scalability, regulatory uncertainty and limited translation from preclinical models to clinical evidence. Overall, marine-derived polysaccharide nanofibers are a promising class of multifunctional wound dressings, but their clinical translation needs stronger standardisation, comparative in vivo evidence, safety validation and manufacturable designs. Full article

Diabetic oral mucosal wounds exhibit impaired healing and require biomaterials with strong wet adhesion, favorable biocompatibility, and adequate mechanical stability. In this study, an in situ photocurable adhesive hydrogel (ATDS) based on sulfonated chitosan was developed for diabetic oral mucosal wound repair. ATDS exhibited a tensile strength of 50 kPa, an elongation at break of 320%, and an adhesive strength of 0.605 MPa, while also displaying a porous microstructure without obvious cytotoxicity. Compared with hyaluronic acid (HA) gel, which was completely lost by day 3, ATDS provided more durable wound coverage in the oral environment. In a diabetic rat model of oral mucosal defect, ATDS significantly accelerated wound closure, with wounds nearly completely healed by day 6, promoted re-epithelialization as early as day 3, and increased epidermis thickness by approximately 50% compared with the control group. In addition, ATDS enhanced angiogenesis and reduced the expression of the inflammatory cytokines TNF-α and IL-1β. Collectively, these findings demonstrate that ATDS effectively promotes diabetic oral mucosal wound healing through its barrier-protective, pro-angiogenic, and anti-inflammatory effects, highlighting its potential as a promising biomaterial for oral tissue engineering and regenerative applications. Full article

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that accumulate in cancer and represent one of the major drivers of tumor-associated immunosuppression. MDSCs actively contribute to tumor progression by inhibiting both innate and adaptive immune responses, promoting angiogenesis, metastatic dissemination, and resistance to immunotherapy. Two major subsets have been identified, polymorphonuclear (PMN-) and monocytic (Mo-) MDSCs, each characterized by distinct phenotypic, metabolic, and suppressive properties. Within the tumor microenvironment (TME), MDSCs establish a complex network of interactions with T-, B-, NK-cells, dendritic cells, and macrophages, thereby orchestrating immune escape and tumor persistence. Recent evidence highlights the pivotal role of metabolic rewiring in regulating MDSC survival and suppressive activity. Enhanced aerobic glycolysis, fatty acid oxidation, amino acid depletion, reactive oxygen species (ROS) production, and adenosine metabolism collectively sustain MDSC-mediated immune dysfunction and shape the immunosuppressive TME. In particular, the crosstalk between PMN-MDSCs and NK cells has emerged as a critical mechanism of tumor immune evasion, leading to impaired NK cell cytotoxicity, altered activating receptor expression, and defective cytokine production. In this review, we summarize the current knowledge on the phenotypic and functional heterogeneity of MDSCs, their metabolic adaptations, and their interactions with immune effector populations in cancer. Furthermore, we discuss emerging therapeutic strategies aimed at targeting MDSC recruitment, differentiation, metabolic pathways, and suppressive functions. Understanding the molecular and metabolic mechanisms governing MDSC biology may provide novel opportunities to overcome tumor-induced immunosuppression and improve the efficacy of current cancer immunotherapies. Full article

Endothelial dysfunction underlies many cardiovascular and metabolic diseases. Lysosomal storage disorders, particularly sphingolipidoses, cause intracellular accumulation of specific sphingolipids due to inherited enzyme defects. This review focuses on Gaucher, Niemann–Pick (types A, B, A/B) and Fabry diseases, selected because they exhibit clinically significant cardiovascular manifestations and each accumulates a distinct sphingolipid—glucocerebroside, sphingomyelin, or globotriaosylceramide—allowing comparative analysis of how different metabolic defects converge on similar endothelial phenotypes. We summarize current knowledge on how substrate accumulation disrupts the ceramide/sphingosine-1-phosphate (S1P) rheostat, affecting NO synthase, vascular permeability, inflammation, angiogenesis, autophagy and cell death. Common and disease-specific changes in endothelial morphology and barrier function are discussed. Importantly, direct experimental evidence for endothelial involvement in Gaucher and Niemann–Pick diseases remains scarce; most mechanistic insights derive from non-endothelial cell models, highlighting a significant gap that underscores the need for targeted endothelial studies. Deficiencies of GBA1, SMPD1, and GLA each modulate S1P and ceramide production through distinct pathways, yet all three conditions share similar functional endothelial alterations driven by disrupted sphingolipid homeostasis. Understanding these common mechanisms opens new perspectives for diagnostic biomarkers and therapeutic strategies aimed at restoring sphingolipid balance in the endothelium, though further research is required to validate these findings in endothelial-specific contexts. Full article

Impaired wound healing arises from interacting biological and material challenges, including persistent infection, biofilm formation, oxidative stress, unresolved inflammation, impaired angiogenesis, defective epithelialization, hemorrhage, and insufficient real-time assessment of wound status. Quantum dot (QD) and nanodot nanosystems have emerged as a versatile class of bioactive wound interfaces capable of addressing these barriers through functions that extend beyond passive coverage. This review synthesizes the design rationale, material composition, validation strategies, functional outcomes, mechanistic interpretation, and translational relevance of QD-enabled platforms for precision wound repair. Across the reviewed literature, carbon dots, graphene QDs, black phosphorus QDs, metal and metal oxide QDs, transition-metal nanodots, and hybrid nanocomposites were incorporated into hydrogels, films, sponges, nanofibers, microneedles, scaffolds, membranes, sprays, and injectable matrices. Their major precision-enabling attributes include localized antimicrobial and antibiofilm activity, redox-adaptive behavior, photothermal and photodynamic activation, inflammatory and macrophage modulation, hemostasis, controlled therapeutic delivery, angiogenic and epithelial support, and fluorescence-based monitoring. The strongest conceptual advance is the transition from static wound dressings toward adaptive biointerfaces that can sense, respond to, or compensate for local wound state abnormalities. Nevertheless, the field remains largely preclinical, with important gaps in long-term safety, standardized characterization, clinically predictive models, manufacturing reproducibility, regulatory alignment, and human validation. Future progress will depend on rationally simplified multifunctional platforms, rigorous comparative testing, wound state-specific evaluation frameworks, and translation-oriented safety and usability studies. QD nanosystems therefore represent a promising foundation for precision wound repair, provided that their multifunctionality is matched by equally rigorous evidence of safety, reproducibility, and clinical relevance. Full article

Diabetic foot ulceration is a severe and common chronic complication of diabetes, accompanied by excessive reactive oxygen species (ROS) accumulation, persistent bacterial infection, prolonged inflammation, and insufficient angiogenesis. Traditional single-function wound dressings fail to simultaneously resolve these pathological barriers, leading to unsatisfactory healing outcomes. In this study, we developed a multifunctional composite hydrogel (E/MGel) by introducing mussel adhesive protein (MAP) into methacrylated hyaluronic acid (mHA) to construct an antibacterial and antioxidant delivery system, which was further loaded with epidermal growth factor (EGF) to promote angiogenesis. The as-prepared E/MGel exhibited a uniform porous structure, favorable rheology, high swelling ratio, and sustained protein release behavior. In vitro results demonstrated that E/MGel exerted potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E.coli), high ROS scavenging efficiency, good cytocompatibility, and remarkable pro-angiogenic effect on endothelial cells. In a mouse model of diabetic MRSA-infected full-thickness skin defect, E/MGel significantly accelerated wound closure, reduced bacterial burden, downregulated pro-inflammatory cytokines, promoted collagen deposition, and enhanced neovascularization. Meanwhile, no obvious systemic toxicity was observed. Taken together, this multifunctional hydrogel integrates antibacterial, antioxidant, and pro-angiogenic capacities to break the pathological vicious cycle of diabetic wounds, providing a promising and safe strategy for the clinical treatment of diabetic infected wounds. Full article

Regulation of the endothelial stress response is important for blood vessel homeostasis and angiogenesis, processes disrupted in common vascular diseases and ageing. Here, we discovered that the Y-box factor ZONAB (ZO-1-associated nucleic acid binding protein; YBX3), a gene associated with risk loci for severe vascular disorders, regulates endothelial homeostasis and angiogenesis. By combining cell-based assays with primary endothelial cells and genome-wide expression and methylation measurements, we found that ZONAB depletion results in mitochondrial deregulation, increased reactive oxygen species, and a defective oxidative stress response, which correlates with increased promoter methylation of cell cycle genes. ZONAB depletion triggered cellular senescence via a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent pathway, which was attenuated by PIK3 inhibitors, an antioxidant, or by drugs targeting mitochondrial function or fragmentation. Thus, our results reveal that ZONAB repression in endothelial cells leads to genome-wide changes in gene expression and DNA methylation, regulating endothelial proliferation and inflammation, as well as mitochondrial deregulation to promote cellular senescence. Hence, ZONAB supports endothelial homeostasis and may play a role in vascular health. Full article

Critical-sized bone defects remain a major reconstructive challenge, and the Masquelet technique has become an important option in traumatic, infectious, and post-resection settings. This review examines the role of acrylic bone cement in this technique, emphasizing its evolution from a temporary spacer to an active biomaterial that shapes the induced membrane and the local regenerative microenvironment. The article discusses the surgical and biological basis of the technique, the composition and handling characteristics of polymethyl methacrylate (PMMA) bone cement, the rationale for antibiotic-loaded spacers, and the influence of spacer-related variables such as formulation, surface properties, and geometry on membrane quality. It also addresses emerging strategies, including bioactive PMMA modifications, multifunctional cements, and degradable alternatives aimed at improving osteogenesis, angiogenesis, and infection control. Current evidence, derived mainly from in vitro studies and animal models, suggests that the spacer may play a role beyond space maintenance by participating in induced membrane formation and influencing biological signaling related to bone repair. In contrast, the clinical evidence primarily supports the reproducible use of PMMA spacers for dead-space management, infection control, and bone reconstruction. However, important gaps still remain in the translational validation of these biological properties and in the standardization of spacer formulations and antibiotic protocols. Full article

Introduction: Chronic wounds and pathologic scars remain a persistent challenge in plastic surgery. Conventional treatments can be costly and inconsistent, prompting interest in regenerative approaches that utilize autologous tissue. Emulsified fat produces nanofat through mechanical processing and contains adipose-derived stem cells, stromal vascular fractions, extracellular matrix proteins, cytokines and growth factors. The purpose of this systematic review is to evaluate the use of autologous nanofat for wound healing and scar management, with emphasis on preparation techniques, treatment indications, and outcomes. Methods: A comprehensive PubMed search with no date restrictions was conducted in January 2026 using MeSH terms and keywords related to nanofat and wound-healing applications. Studies were screened independently by two reviewers using the Rayyan platform. Eligible studies evaluated nanofat for wound healing in human or animal subjects; non-English articles, studies not involving nanofat, editorials, and conference abstracts were excluded. The extracted data included study characteristics, participant numbers, treatment details, indications, adjunct therapies, follow-up duration, outcomes, and complications. Studies were grouped by clinical application, with individual reports included in multiple categories when relevant. Results: The search identified 53 records, of which 22 studies met the inclusion criteria after screening. These included 20 human and two animal studies spanning randomized controlled trials (n = 3), prospective trials (n = 6), retrospective analyses (n = 6), case series (n = 4), and case reports (n = 3). Mechanical emulsification was the predominant autologous nanofat preparation method (91%), often combined with filtration or centrifugation. Clinical indications in human studies were diverse, most commonly including scar treatment (n = 14) (acne, burns, depressed, and post-surgical), followed by chronic wounds (n = 3) and reconstructive applications (n = 3). Nanofat was administered via injection in 86% of studies (n = 19), typically using fine-gauge needles or microcannulas with intradermal or subdermal placement, while three studies used non-injection approaches such as topical, membrane, or dressing-based delivery. Scar or aesthetic parameters, measured using VSS, POSAS, physician grading, photography, pigmentation analysis, or clinical appearance, were evaluated in 73% of studies (n = 16), and all reported improvement in variables such as pigmentation, pliability, thickness, texture, or overall appearance. Wound-healing endpoints were assessed in 36% (n = 8), with 100% (n = 8) demonstrating accelerated healing, improved epithelialization, or defect closure. Patient-reported outcomes, including satisfaction or quality of life, were measured in 32% (n = 7), and all showed improvement. Objective imaging modalities (e.g., 3D imaging, ultrasound, angiography, digital analysis) were used in 23% (n = 5), each confirming structural or physiologic improvement. Histologic or biomolecular analyses were performed in 27% (n = 6) and uniformly demonstrated regenerative changes, such as increased angiogenesis, collagen remodeling, or growth factor expression. Treatment was well tolerated, with 77% of studies (n = 17) reporting minimal or no complications and only transient mild adverse effects, including mild pain, bruising, erythema, and edema. Conclusions: Current evidence suggests that autologous nanofat is a promising regenerative therapy for wound healing and scar modulation. Across diverse clinical applications, nanofat has been associated with improved tissue quality, enhanced healing, and favorable patient-reported outcomes, with minimal complications. The mechanical processing of autologous tissue may also involve fewer regulatory concerns compared with more extensively manipulated cellular products. Full article

The present study investigated the effect of a 3D-printed nanocomposite scaffold on bone healing in vivo. The scaffolds used were made from the bioresorbable thermoplastic polycaprolactone polymer, blended with Multi-Walled Carbon Nanotubes functionalized with chitosan, and manufactured with a rectilinear infill pattern and interconnected pores of 500 μm in size. The study included three groups of 10 Wistar rats, in which a 2 mm bone defect was created in the middle of the right femur. In the scaffold/peptide group, the gap was filled with the scaffold loaded with a peptide corresponding to human pleiotrophin amino acids 48-56 (PTN_48-56), and the fracture was stabilized with a 12 mm K-wire as an intramedullary nail. In the scaffold group, the scaffold did not contain the peptide, and in the control group, the bone defect was stabilized without the use of a scaffold. Radiological examination revealed that bone healing was achieved on average in 6.6 weeks in the scaffold/peptide group, 7.2 weeks in the scaffold group, and 8.1 weeks in the control group. Histopathological examination performed 2 weeks postoperatively showed that angiogenesis in the scaffold/peptide group was 1.5 times higher than in the scaffold group and 2.5 times higher than in the control group. In conclusion, our osteo-inductive 3D-printed scaffold covered with PTN_48-56 is a promising option for accelerating bone defect healing. Full article

Icariin (ICA), a prenylated flavonoid glycoside from Epimedium (Yin Yang Huo), exhibits multi-organ pharmacological effects and has emerged as a promising candidate for osteoporosis therapy and bone tissue regeneration because of its capacity to modulate diverse osteogenic, anti-inflammatory, and angiogenic signaling pathways. Preclinical studies in osteoporotic models suggest that ICA improves trabecular microarchitecture and increases bone mineral density. Mechanistically, ICA modulates bone remodeling bidirectionally: it promotes osteoblast differentiation and extracellular matrix mineralization via activation of pro-osteogenic pathways, including Wnt/β-catenin and PI3K/Akt signaling, while simultaneously inhibiting osteoclastogenesis and bone resorption by suppressing RANKL-mediated NF-κB activation, thus reestablishing remodeling equilibrium. Despite these benefits, clinical advancement is hindered by the suboptimal oral bioavailability of ICA, stemming from poor intestinal absorption and extensive first-pass metabolism. To address this, innovative delivery systems have been engineered to enhance localized bioavailability and sustain therapeutic efficacy, such as hydrogel depots, nanoparticle formulations, and 3D-printed scaffolds enabling precise, controlled release. In bone tissue engineering applications, ICA-incorporated biomaterials—either standalone or in combination with osteogenic factors or exosomes—foster a regenerative niche by mitigating inflammation and oxidative stress, while synergistically promoting osteogenesis and angiogenesis, thereby expediting bone defect healing and osseointegration. Overall, these mechanistic elucidations and delivery advancements underscore ICA’s potential as a translational candidate for osteoporosis treatment and bone regenerative therapies. This review aims to critically and systematically synthesize current evidence on ICA-mediated bone repair and regeneration, with a particular emphasis on the molecular regulation of osteogenic signaling, the restoration of bone-remodeling homeostasis, and delivery-system-enabled strategies that may facilitate translational application. Full article

Bone tissue plays a vital role in the human body and possesses intrinsic self-repair mechanisms; however, large defects or pathological fractures may exceed its natural healing capacity. Bone tissue engineering provides promising strategies to restore bone integrity through the use of scaffolds, growth factors, and stem cells. While calcium phosphate (CaP)-based ceramics, such as hydroxyapatite (HAp) and tricalcium phosphate (TCP), represent the current benchmark, their limitations, including slow degradation (HAp) and limited osteoinductivity (TCP), have driven the development of alternative biomaterials. In this context, magnesium phosphate (MgP)-based materials have gained increasing attention due to their tunable resorption rate, improved biodegradability, and ability to stimulate osteogenesis and angiogenesis through the release of magnesium (Mg²⁺) ions. This study reports on composite scaffolds based on electrospun poly(ε-caprolactone) (PCL) fibres coated with MgP layers doped with lithium (Li) and zinc (Zn), designed to mimic the nanofibrous architecture of the extracellular matrix. Lithium and zinc were selected due to their known ability to modulate cellular response, with lithium promoting osteogenic activity and zinc contributing to improved cell proliferation and antibacterial potential. The phosphate phases obtained by coprecipitation were deposited onto the PCL fibres using Matrix-Assisted Pulsed Laser Evaporation (MAPLE), enabling controlled surface functionalization. Following thermal treatment, the formation of the crystalline magnesium pyrophosphate (Mg₂P₂O₇) phase was confirmed by chemical and structural characterization. The combination of a slowly degrading PCL matrix, providing sustained structural support, and a bioactive MgP coating, enabling rapid and controlled ion release, results in improved scaffold performance in terms of biocompatibility, biodegradability, and bioactivity. While the slow degradation rate of PCL ensures mechanical stability over an extended period, the surface-deposited MgP phase allows immediate interaction with the biological environment, facilitating faster ion release and enhancing cell–material interactions. These findings highlight the potential of the developed composites as promising candidates for trabecular bone regeneration and as viable alternatives to conventional CaP-based scaffolds in regenerative medicine. Full article

Critical-sized bone defects represent a major clinical challenge, as defects of this magnitude do not heal spontaneously without regenerative intervention. This study aimed to evaluate the osteoinductive effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded β-tricalcium phosphate (β-TCP) scaffolds on bone regeneration and vascularization in a rabbit calvarial critical-sized defect model. Eighteen male New Zealand White rabbits were used, and four standardized circular defects (5 mm in diameter) were created in the calvaria of each animal. The defects were assigned to four groups: control (unfilled), β-TCP + 5 µg rhBMP-2, β-TCP + 10 µg rhBMP-2, and β-TCP + 20 µg rhBMP-2. Bone healing was evaluated at 2, 4, and 8 weeks using histological, histomorphometric, and cluster of differentiation 31 (CD31) immunohistochemical analyses. The results demonstrated that rhBMP-2–loaded β-TCP scaffolds significantly enhanced bone regeneration compared with the control group, with a progressive increase in bone formation observed with increasing rhBMP-2 doses. The β-TCP + 20 µg rhBMP-2 group exhibited the highest levels of new bone formation, more advanced bone maturation, improved collagen organization, and increased vascularization. However, no statistically significant differences were observed between the 10 µg and 20 µg groups at later time points (p > 0.05), suggesting a dose-dependent saturation (plateau) effect. In conclusion, rhBMP-2–loaded β-TCP scaffolds promote bone regeneration and angiogenesis in a dose-related manner up to a threshold, beyond which additional increases in dose do not result in proportional improvements. These findings emphasize that optimal rhBMP-2 dosing is critical to maximize regenerative outcomes while avoiding unnecessary dose escalation. Full article

Treatment for large critical-sized bone defects and impaired fracture healing remain challenging. Clinically used protein-based osteoinductive factors, such as recombinant bone morphogenetic proteins (BMPs), can be effective; however, they are costly and limited by stability, dose-delivery issues, and safety concerns. Preclinical small molecules offer an alternative because they are chemically stable, scalable to manufacture, and readily integrated for systemic administration or localized release from scaffolds, hydrogels, cements, and implant coatings. With an emphasis on delivery formats and mechanistic themes, this review examines small molecules that have been shown to improve bone regeneration in preclinical models, contrasting those of biological origin with synthetic and repurposed compounds. Across studies, these selected compounds promote osteoblast commitment, differentiation, and matrix mineralization via BMP/Smad signaling and Wnt/beta-catenin (β-catenin) activation, often through glycogen synthase kinase-3 beta (GSK-3β) inhibition or relief of pathway antagonism or Hedgehog (Hh) pathway stimulation. Beyond osteoinduction, several candidates address issues that commonly limit repair, including angiogenesis, oxidative stress, inflammatory tone, osteoimmune regulation, and suppression of osteoclast-mediated resorption. Direct head-to-head comparisons are rare across both classes and reporting heterogeneity complicates interpretation. Key translational gaps include limited cytotoxicity and immunologic profiling, dose and release optimization, durability of benefit, and insufficient evaluation of rational combinations. More rigorous in vivo studies, including larger animal models and standardized outcome metrics, are needed to prioritize promising candidates and guide clinical development. Full article