ABSTRACT Full‐thickness skin defects involving tendon or bone exposure present significant clinical challenges owing to inadequate vascularity, which renders spontaneous wound healing unlikely. Conventional treatments using autologous flap transplantation may incur donor‐site morbidity. Dermal substitutes are employed to enhance wound bed construction and improve skin graft survival by promoting vascularization and extracellular matrix (ECM) deposition. However, currently available substitutes are predominantly composed of purified bovine‐ or porcine‐derived type I collagen and lack the bioactive components. Urinary bladder matrix (UBM), a naturally derived scaffold, contains a rich repertoire of ECM constituents that effectively promote the healing process, offering a potential novel approach for dermal regeneration. Nevertheless, human histological evidence on UBM in tendon/bone‐exposed wounds remains limited. In this study, we compared the efficacy of UBM wound matrix (ExceFil Biological Wound Matrix, ZhuoRuan Medical Technology) with that of artificial dermal substitute (Pelnac, GUNZE Medical Division) in treating extremity wounds with tendon/bone exposure in a series of six clinical cases. Clinically, both products successfully promoted wound vascularization and graft survival. Histological analysis revealed that the UBM group exhibited superior regenerative features, including enhanced fibroblast migration, collagen deposition, neovascularization, and immunomodulatory properties, with a higher rate of M2 macrophage polarization at 15 ± 2 days post‐implantation. Furthermore, RNA sequencing demonstrated that the UBM matrix significantly upregulated pathways related to cytokine‐cytokine receptor interaction and chemokine signaling, both of which modulate immune and regenerative processes within the wound microenvironment. These findings suggest that UBM biological matrix represents a promising dermal substitute for promoting regenerative healing in tendon/bone‐exposed wounds.
Hybrid hydrogels that integrate mechanical tunability with biological activity are critical for regenerative medicine. Oligo(poly(ethylene glycol) fumarate) (OPF) offers controllable network formation but lacks intrinsic cell affinity. Here, we incorporated gelatin methacrylate (GelMA) into OPF networks to develop an interpenetrating network (IPN) hybrid OPF-GELMA hydrogel that combines the mechanical versatility of OPF with the bioactivity of GelMA. The crosslinked hydrogels with varying GelMA content exhibited GelMA-dependent modulation of swelling, gel fraction, compressive stiffness, and microstructure. Increasing GelMA concentration reduced water uptake while significantly enhancing mechanical strength and proliferation of rat bone marrow-derived mesenchymal stem cells (rBMSCs). Moreover, GelMA incorporation markedly enhanced rBMSC osteogenic differentiation, as demonstrated by elevated alkaline phosphatase activity and increased Runx2 expression. These results demonstrate that OPF-GELMA hydrogels enable synergistic regulation of biochemical and mechanical cues, providing a versatile scaffold platform for bone tissue engineering and regenerative medicine applications.
Renal failure remains a leading cause of morbidity and mortality, as current renal replacement therapies restore filtration but fail to replicate the kidney's transport, metabolic, and endocrine functions. Bioengineered systems using primary renal epithelial cells show promise in recapitulating these processes, and integration into synthetic tubular platforms may further enhance biological mimicry, advancing drug discovery, and next-generation bioartificial kidneys. The native proximal tubule basement membrane contains aligned ridges (~200 nm), suggesting that scaffold fiber alignment could improve epithelial cell function. We therefore hypothesized that aligned electrospun fibers would promote proximal tubule epithelial cell organization and enhance functional performance compared to random fibers. Polycaprolactone scaffolds with random or aligned fibers were fabricated in both flat and tubular configurations using solution electrospinning (SES). Human renal proximal tubule epithelial cells (HRPTEpiC) were cultured for up to 11 days and assessed for morphology, barrier function, polarization, and transporter expression. Aligned fibers induced cytoskeletal organization but did not affect tight junction formation, polarization, or monolayer formation. Barrier function was significantly reduced on aligned scaffolds at Day 11, attributed to larger pore sizes (15.3 vs. 7.5 μm2). Transporter expression showed transient differences, with ATP1A1 and AQP1 reduced on aligned scaffolds at Day 7 but equalized by Day 11. Functional transport assays revealed significant ABC transporter inhibition only on random scaffolds (p = 0.048 vs. p = 0.058 for aligned). Overall, these findings show that at the tested diameters (1.2-1.6 μm), fiber alignment influenced cell morphology but offered limited functional benefit compared to random fibers.
Barrier membranes are used in guided bone regeneration (GBR) to prevent the migration of fibroblastic cells into the alveolar bone defects and to ensure the regeneration of bone tissue. The regeneration capabilities of alveolar bone tissue and connective tissue are different, so the niche required by the tissues must also meet this need. In this study, a bilayer synthetic polymeric barrier membrane containing 45S5 bioactive glass (BG) was prepared by the electrospinning method to provide regeneration of both tissues. A fibrous layer was fabricated using polyvinyl alcohol (PVA) containing 3% BG for the soft tissue interface, and a second fibrous layer was fabricated on top of this layer using poly(lactide-co-glycolide) (PLGA) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) blend polymers containing 10% BG for the hard tissue interface. It has been demonstrated that bilayer nanofiber membranes show suitable mechanical, thermal, and physicochemical properties for using GBR applications, as well as high bioactivity and suitable bioresorbable properties. In vitro and in vivo animal study biological assays have demonstrated that nanofibrous multilayer dental membranes are highly biocompatible with fibroblast and bone cells, accelerate cell proliferation, and increase cell adhesion to the membranes. It has been demonstrated that the designed bioactive bilayer nanofiber membranes can meet the requirements for use as a support material in GBR applications in dentistry.
Extracellular amyloid plaques from Aβ accumulation and intracellular neurofibrillary tangles (NFTs) from hyperphosphorylated Tau (p-Tau), both leading to neuronal dysfunction, synapse loss, and cognitive decline. Nonetheless, achieving an effective therapeutic outcome is challenging due to the limited drug bioavailability through the blood-brain barrier (BBB) and the complex microenvironment within the brain. This study proposes MM-TA for the synergistic treatment of AD, utilizing mesoporous manganese (MM) as a nanocarrier to deliver a LK7 (Aβ-inhibiting peptide) and a DAA (amino acid-peptide) that inhibits Tau-related fibrils formation. A biomimetic nanocarrier (MM-LD@4CM termed as MLDC) encapsulated with 4T1 cell membranes (4CM) was developed, inspired by 4T1 cells' ability to facilitate BBB penetration. Following traversal of the BBB, MLDC concurrently prevented Tau phosphorylation and suppressed Aβ aggregation. Furthermore, by leveraging MM's catalase-mimetic properties, MLDC mitigated oxidative stress and altered the microenvironment associated with AD progression. In contrast to the singular therapeutic agent, MLDC ameliorated nerve damage and enhanced cognitive function in AD mice by reducing Aβ oligomers, phosphorylated Tau, and inflammation, thereby providing a synergistic therapeutic approach with significant potential for effective AD treatment.
Observational studies have shown that human teeth with higher concentrations of titanium traces have better optical properties. The aim of this study was to investigate how titanium ion infiltration into tooth enamel affects its optical properties by studying the diffusion and reactivity of titanium compounds in tooth enamel and how this affected enamel optical properties. Tooth enamel specimens were incubated in hydrophobic solutions of titanium isopropoxide. The effect of the treatments on surface composition, topography, enamel hardness, shade, and crystallinity were assessed. Exposing enamel to hydrophobic solvents dissolved part of the acquired enamel pellicle proteins and increased the reactivity of the enamel surface. This allowed the penetration of organic titanium ions deep into dental enamel, which increased the tooth whiteness. The findings of this study will set the basis towards new dental therapies based on titanium modification of enamel tooth structure.
Because its elastic modulus is closer to that of cortical bone, polyetheretherketone (PEEK) has been considered a potential alternative to titanium for dental implants. However, the biological inertness and lack of intrinsic antibacterial activity of pristine PEEK limit its osseointegration and increase the risk of peri-implant infection. In this study, Zn-, Mg-, and Zn/Mg-implanted PEEK were prepared using a metal vapor vacuum arc ion source, with untreated PEEK as the control. Surface chemical composition, ion release, roughness, and wettability were characterized, and the osteogenic responses of MG-63 cells and antibacterial activity against Staphylococcus aureus and Fusobacterium nucleatum were evaluated. Ion implantation introduced Zn and/or Mg into the near-surface region of PEEK and was accompanied by increased surface roughness and improved hydrophilicity. Mg-containing surfaces, particularly the Zn/Mg group, promoted cell spreading, proliferation, alkaline phosphatase activity, and the expression of osteogenesis-related genes, including ALP, IBSP, and BGLAP. Antibacterial activity was more evident on Zn-containing surfaces, whereas Mg alone showed only limited antibacterial effects. Although Zn alone showed stronger inhibition of Fusobacterium nucleatum, Zn/Mg co-implantation achieved a more favorable overall balance between osteogenic and antibacterial performance. Zn/Mg co-implantation improved osteogenesis-related responses while adding antibacterial activity to PEEK surfaces, suggesting its potential as a coating-free modification strategy for PEEK-based implant materials.
Critical-sized bone defects (CSDs) represent a major clinical challenge due to their limited self-healing capacity. Conventional hydrogels incorporating crystalline hydroxyapatite (HA) often fail to recapitulate the hierarchical nanostructure of native bone, leading to suboptimal regeneration outcomes. To overcome this, we developed a biomimetic hydrogel by molecularly integrating amorphous calcium phosphate oligomers (CPO) into gelatin methacryloyl (GelMA), enabling a bone-like organic-inorganic hybrid network. This composite exhibits outstanding performance: an ultimate strength of 192 kPa at 18 wt% CPO confirms robust mechanical reinforcement, while 54% mass retention after 56 days underscores exceptional degradation resistance and dose-dependent bioactivity, evidenced by a two-fold upregulation of alkaline phosphatase (ALP) activity. The amorphous CPO facilitates biomimetic HA nucleation within the GelMA matrix, mimicking the natural mineralization process. In a rat calvarial CSD model, the hydrogel promoted 60% bone volume regeneration within 12 weeks, significantly outperforming conventional composites, through seamless host integration, vascularized trabecular bone formation, and a collagen-mineral hierarchy resembling native osteogenesis. This study establishes CPO as a transformative component that converts passive scaffolds into bioactive osteogenic microenvironments, offering a clinically viable strategy for complex bone regeneration.
Effective skin repair and photoprotection require multifunctional, simple, and ready-to-use biomaterials. We focused on natural tea trichomes (TH), a class of plant-derived microfilaments abundantly distributed on tea leaves, as a potential candidate biomaterial that fulfills these criteria. TH exhibited a uniform fibrous morphology with a diameter of approximately 9.1 μm and a high polyphenol content of 176 μg/mg. In vitro ABTS+ and DPPH assays confirmed its effective radical scavenging capacity. In vivo studies demonstrated rapid hemostasis with negligible hemolysis, underscoring its biosafety. In a murine full-thickness wound model, TH significantly accelerated tissue regeneration, achieving 88.9% wound closure on day 10 versus 77.6% in controls, by promoting M1-to-M2 macrophage polarization, enhancing collagen deposition, and stimulating hair follicle neogenesis. Furthermore, TH, whether applied alone or blended into a hyaluronic acid (HA) matrix, effectively mitigated UV-induced epidermal hyperplasia, collagen degradation, and inflammatory cytokine expression. This work demonstrates that TH can serve as a sustainable, multifunctional platform for skin repair, with regenerative and photoprotective properties as its primary demonstrated functions.
Advanced wound care increasingly demands materials that can both integrate safely with tissue and support next-generation programmable functions. Recombinant protein biomaterials offer unique opportunities for designing adaptive wound dressings; however, their inherent susceptibility to host proteases presents a critical challenge, as protein-based materials may act as competitive substrates that alter proteolytic flux and potentially impede healing. Here, recombinant honeybee silk (F1-4) films were evaluated for protease susceptibility and biocompatibility, and wound-healing effects were assessed in a preclinical murine excisional wound model. The material was well tolerated, with no adverse events and no detrimental impact on final wound closure or early scar formation. Subtle, transient effects were observed during the inflammatory and proliferative phases, including modestly slower wound closure between days 7-13 and thinner epidermal coverage at day 14, with histological differences most pronounced at day 7. While recombinant honeybee silk was susceptible to host-relevant proteases in vitro, protease activity was not directly measured in wound tissue or exudate. Therefore, the observed transient differences in healing are consistent with, but do not establish, the hypothesis that the material may act as a modest competitive substrate during the proliferative phase. Importantly, this did not impair overall healing outcomes. Together, these results establish foundational safety evidence and highlight recombinant honeybee silk as a promising platform for engineering advanced, responsive healthcare materials for clinical wound management.
Despite the success of total knee arthroplasty (TKA), a small percentage of devices fail. Due to the high volume of surgeries performed each year, revision total knee arthroplasty surgery presents a burden on patients and surgeons. One aspect that may improve TKA outcomes is device design, specifically the use of grit blasting to increase the surface roughness. This is a common design feature seen in TKA where grit blasted instruments and implants such as the tibial tray will be utilized during the surgery. Other components in the implant system include a polyethylene tibial insert, patellar component, and a polished femoral component. Grit blasting is a process that propels alumina grit at a high velocity to plastically deform the surface. Often, residual alumina remains embedded in the surface of the implant. In this exploratory study we evaluated the amount of alumina found on 21 explanted CoCrMo femoral components paired with 21 CoCrMo grit blasted tibial components. We asked (1) what are the potential sources of alumina in the implant system, (2) what mechanisms may be causing the potential migration of alumina to the femoral component, and (3) is the amount of alumina contamination on the CoCrMo femoral component clinically relevant? Using optical microscopy, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS) we evaluated the surfaces of the explants. In SEM images taken at 500× magnification, we saw that an approximate area fraction of 34% ± 9% of the tibial components' surface was embedded with residual alumina from the grit blasting process. Alumina debris identified as third body wear particles were seen on the bearing surface of 17/21 (81%) of the femoral components. We found alumina on the posterior condyles of 13/21 (62%) of the implants. Finally, we saw large amounts of imparted alumina on devices where the polyethylene had worn and the tibial components were suspected to have made direct contact with the CoCrMo femoral components. Our results suggest that residual alumina from the grit blasting process may result in alumina third body wear particles being released onto the bearing surface of retrieved knee implants.
Titanium implants are widely used in orthopedics and spinal surgery, but implant-associated infections remain a major clinical challenge that often necessitates implant removal. To address this issue, we evaluated whether an iodine-loaded porous titanium implant with a gradient pore design could balance antibacterial activity and bone formation. The structure transitions from large outer pores to smaller inner pores, enhancing osseointegration while providing a greater surface area for iodine ion loading. Implants were fabricated by selective laser melting and surface-modified to incorporate iodine ions. In vivo experiments using rabbit femoral condyles demonstrated that gradient implants (Ti-D) showed bone ingrowth comparable to larger pore implants at 4 weeks. Iodine-treated implants (ITi-D) exhibited sustained ion release, strong antibacterial activity against Staphylococcus aureus and Escherichia coli, and no clear cytotoxicity in vitro. In vivo subcutaneous infection models confirmed significant antibacterial efficacy of ITi-D, while blood tests showed no systemic toxicity up to 90 days. Compared with uniformly porous implants, ITi-D achieved an optimal balance between antimicrobial performance and biocompatibility. This dual-functional approach addresses the longstanding tradeoff between infection control and osseointegration in porous titanium implants.
Polystyrene microplastics (PS-MPs) are emerging environmental contaminants with increasing evidence of systemic toxicity; however, the mechanisms underlying their hepatic effects remain incompletely understood. The present study investigated the hepatotoxic effects of PS-MPs, focusing on hepatic bioaccumulation, mitochondrial homeostasis, inflammation, apoptosis, and liver functional impairment. Experimental animals were exposed to increasing concentrations of PS-MPs, after which liver tissues were subjected to GC-MS, biochemical, histopathological, and molecular analyses. GC-MS confirmed hepatic accumulation of PS-MPs predominantly in the higher exposure groups (20 and 40 μg), which were subsequently selected for mechanistic investigations. PS-MP exposure induced marked hepatic dysfunction, evidenced by elevated bilirubin, ALT, AST, and GGT levels together with significant reductions in total protein, albumin, and globulin concentrations. Histopathological examination revealed progressive hepatocellular degeneration, inflammatory infiltration, cytoplasmic vacuolation, and necrotic alterations. In parallel, inflammatory and apoptotic signaling were significantly activated, as demonstrated by increased NF-κB and caspase-3 levels. Mechanistically, PS-MPs were associated with transcriptional dysregulation of genes involved in mitochondrial homeostasis, including suppression of mitochondrial biogenesis markers (PGC-1α and TFAM), downregulation of mitochondrial fusion regulators (MFN2 and OPA1), increased DRP1 expression, and reduced PINK1 expression, suggesting altered mitophagy-related signaling. Principal Component Analysis further demonstrated clear separation between control and exposed groups, strongly associating PS-MP exposure with hepatic injury, transcriptional dysregulation of mitochondrial homeostasis-related genes, inflammation, and apoptosis. Collectively, these findings demonstrate that PS-MPs induce significant hepatotoxicity, accompanied by coordinated transcriptional dysregulation of mitochondrial homeostasis-related genes and activation of inflammatory and apoptotic pathways. These findings highlight the liver as a major target of microplastic toxicity and emphasize the need for further studies incorporating protein-level validation, functional mitochondrial assessments, and long-term exposure models to better understand the implications for human health.
β-tricalcium phosphate (β-TCP) is widely used as a bone substitute because of its biocompatibility, osteoconductivity, and biodegradability; however, its brittleness and limited adaptability to irregular bone surfaces may restrict its performance in spinal fusion. This study aimed to evaluate whether a β-TCP/collagen composite scaffold could enhance osteogenesis and promote sustained bone remodeling in a sheep lumbar interlaminar fusion model. β-TCP/collagen composite scaffolds and β-TCP scaffolds were compared in vitro using MC3T3-E1 osteogenic precursor cells. Cell adhesion, proliferation, apoptosis, extracellular matrix mineralization, and osteogenic differentiation were assessed by scanning electron microscopy, CCK-8 assay, flow cytometry, alizarin red staining, alkaline phosphatase staining, RT-qPCR, and western blotting. In vivo, β-TCP and β-TCP/collagen scaffolds were implanted into the L3-L4 and L4-L5 interlaminar spaces, respectively, in a self-controlled sheep model. Bone formation and remodeling were evaluated by X-ray, micro-CT, and Van Gieson staining at 3, 5, and 8 months after surgery. The β-TCP/collagen scaffold showed a porous collagen-containing structure that supported greater MC3T3-E1 cell spreading and pseudopod extension than β-TCP alone. Cell proliferation on the β-TCP/collagen scaffold was significantly increased from day 3, whereas apoptosis remained low in all groups, with apoptotic cells accounting for less than 5%. Alizarin red and alkaline phosphatase staining showed more pronounced extracellular matrix mineralization in the β-TCP/collagen group. RT-qPCR and western blotting further demonstrated enhanced expression of osteogenic markers in the β-TCP/collagen group compared with β-TCP alone. In the sheep lumbar interlaminar fusion model, radiological, and histological analyses showed more sustained new bone formation and more organized trabecular remodeling in the β-TCP/collagen group. The β-TCP/collagen composite scaffold enhanced osteogenic activity in vitro and promoted more sustained bone remodeling in a sheep lumbar interlaminar fusion model compared with β-TCP alone. These findings suggest that β-TCP/collagen scaffolds may provide a clinically relevant biomaterial strategy for posterior spinal fusion, although further studies are needed to clarify the mechanisms underlying scaffold-mediated vascularized bone remodeling.
Chronic wounds remain a significant clinical challenge, primarily because of persistent obstacles including prolonged healing duration, high recurrence rates, and limited responsiveness to standard therapies. These limitations impose a considerable burden, which severely affects patients' quality of life. Autologous platelet-rich fibrin has emerged as a promising regenerative strategy to overcome these challenges; however, its clinical utility is restricted in patients with underlying conditions such as diabetic foot ulcers or impaired platelet function. In this context, allogeneic platelet-rich fibrin has been proposed as a promising therapeutic alternative, offering distinct advantages in selected patient populations. This study provides a comparative evaluation of autologous versus allogeneic platelet-rich fibrin in the management of persistent wounds, specifically assessing wound area reduction, granulation tissue score quality, and time of healing. Seventeen patients with prolonged, chronic non-healing wounds were assigned to two groups: autologous platelet-rich fibrin (n = 6) and allogeneic platelet-rich fibrin (n = 11). Despite a significant difference in pre-treatment wound duration (6 vs. 13 weeks, p < 0.05), both groups showed a remarkable reduction in wound area, from a median of 7.50 to 1.25 cm2 within 2 weeks, with no statistical difference in healing rates (p > 0.05). Granulation tissue scores improved markedly post-treatment, with 64.71% of patients achieving a score of 4/5, regardless of the source. Autologous platelet-rich fibrin demonstrated a faster complete healing time (30.67 vs. 48.27 days, p < 0.05). Treatment with allogeneic platelet-rich fibrin on a diabetic foot ulcer resulted in an 85.7% reduction in affected area, reaching complete closure within a five-week period. The findings show that while both groups are equally proficient in stimulating wound closure and tissue regeneration, the autologous method may accelerate the final stage of the healing process. This research encourages the broader use of allogeneic alternatives, particularly for patients with insufficient autologous blood, without compromising healing quality.
Once known as a toxic gas, hydrogen sulfide (H2S) is now making its way into many therapeutic applications. Similar to its other fellow endogenous gasotransmitters, nitric oxide and carbon monoxide, H2S is a small gas with a short half-life, making it extremely capable of penetrating through cell membranes quite easily and fast via gas exchange. This fundamental small molecule possesses many physiological and pathological functions and is found in almost every mammalian system, such as the cardiovascular system, the integumentary/skin system, the neural system, the gastrointestinal tract system, and the skeletal system. As a therapeutic, the gas can modulate biological pathways, maintain homeostasis under physiological conditions, and mediate several pathological processes, thereby supporting cardioprotective applications. Due to the ever-increasing cardiovascular complications, especially concerning myocardial infarction and atherosclerosis, more and more patients are suffering from heart failure, and in some cases, this results in death. To remedy the progression of cardiovascular complications and cardiovascular disease burden as a whole, H2S has emerged as a potential candidate to mediate this problem. This review will specifically focus on the therapeutic potential of H2S-releasing platforms tailored to aid in cardiovascular applications.
Tendon injuries remain a major clinical challenge due to the tissue's limited regenerative capacity and poor remodeling of current allograft-based therapies. To address these limitations, we developed a tendon-derived thread (TDT) scaffold by electrocompacting decellularized tendon powder into aligned threads, which were subsequently woven into a porous overlay patch. Biochemical analyses of TDT confirmed efficient decellularization (DNA < 50 ng/mg) and the preservation of collagen and proteoglycans. Compared to en bloc human tendon graft (HTG), the TDT scaffold exhibited significantly higher swelling ratios and greater weight loss over 8 weeks in vitro, indicating greater porosity and faster degradation. In a rabbit infraspinatus partial-thickness fenestration injury model, the TDT scaffold and HTG were sutured over the injury and evaluated at 2 and 8 weeks to observe tissue infiltration and in vivo response to biomaterial degradation during early phases of healing. Biomechanical testing of shoulders showed no significant differences in load relaxation, ultimate tensile strength, and stiffness among intact, HTG, and TDT scaffold groups in this injury model, suggesting comparable mechanical restoration. Histological and gross observations indicated progressive resorption of TDT scaffolds, which were infiltrated by cells at 2 weeks, and neotissue formation was evident by 8 weeks. In contrast, cell infiltration into the allograft was limited at both time points, and there was no evidence of degradation in vivo. These findings support the potential of the TDT scaffold as a degradable scaffold to support tendon healing during injury.
Highly crosslinked polyethylene (XLPE) has revolutionized total hip arthroplasty (THA), but increased radiation doses and complex crosslink structures may increase oxidation susceptibility. The long-term oxidative stability of XLPE depends on manufacturing factors, including crosslink density, antioxidant (vitamin E) concentration, incorporation method, and radiation parameters. This study examined their interplay in current-generation XLPE acetabular liners produced by sequential irradiation and annealing, vitamin E diffusion, or grafting under extended accelerated aging. XLPE liners were thermally aged at 70°C in 5 atm oxygen for up to 18 weeks. Raman and Fourier-transform infrared spectroscopy were used to assess oxidative degradation via oxidation index (OI), trans-vinylene index (TVI), vitamin E index (VEI), and phase composition. Sequentially irradiated and annealed XLPE showed a sigmoidal OI increase with post-aging crystallization, indicating structural reorganization and potential embrittlement. In contrast, all vitamin E-stabilized XLPEs (0.1-0.7 wt%) maintained negligible OI values. Although an inverse correlation between VEI and OI was not strictly observed, OI increased with TVI, suggesting that higher crosslink density may increase oxidation susceptibility despite overall negligible oxidation. Vitamin E-diffused XLPEs exhibited greater antioxidant depletion than grafted variants but demonstrated comparable oxidation resistance. These findings highlight the inherent limitations of sequentially irradiated and annealed XLPE in resisting oxidation due to persistent residual free radicals, whereas vitamin E stabilization, either by diffusion or grafting, effectively suppressed oxidation and preserved XLPE integrity. Although formulations differed in vitamin E concentration, incorporation route, and radiation source, these factors exerted only secondary influence once approximately 0.1 wt% vitamin E was incorporated.
The biocompatibility of bioresorbable ceramics is critically influenced by the interplay between ceramic resorption and bone formation. This study presents a mathematical framework to quantitatively model the competition between these processes using beta-tricalcium phosphate (β-TCP) as a model system. Such a framework incorporates the paracrine and autocrine signaling interactions among osteoblasts and osteoclasts. While analysing in vivo data (sheep model), the temporal dynamics of bone formation and ceramic resorption are evaluated. The model predictions align closely with the experimental results, capturing key biophysical mechanisms. Apart from fitting with empirical models, the bone growth kinetics data of the published studies follow Hill's model closely, which is regarded as the foundation of quantitative pharmacology. While analysing its physiological relevance, the parametric sensitivity analysis reveals the dominant influence of osteoclast removal rates and specific signaling pathways (osteoblast-to-osteoblast and osteoblast-to-osteoclast) on bone growth. The competition between bone growth and β-TCP resorption leads to a cross-over at 6 weeks, which correlates well with the time period to produce the half-of-the-maximum bone growth as per Hill's model. These findings provide insights into optimising the design of bioresorbable ceramics for clinical applications, emphasising the tailoring of resorption rates to support bone growth, in vivo.
Radiofrequency ablation (RFA) is an effective strategy in realizing targeted lesions. However, its application for highly heterogeneous tissues like lipid-rich atherosclerotic plaques remains challenging due to its strong dependence on Joule heating. Current electrosensitizers used to enhance radiofrequency (RF) energy deposition are limited by their reliance on passive diffusion and random distribution. In this study, inspired by Geobacter OmcZ nanowire networks, electrosensitive atherosclerosis-targeting self-assembled peptides (EASPs) are designed as RF sensitizers to improve the heat deposition in lipid-rich plaques. Based on a targeting motif and a self-assembling module, EASPs accumulate in inflammatory regions of the aorta via recognition-induced self-assembly, resulting in in situ network aggregation. Taking advantage of the rapid amplification of nanofiber networks triggered by vascular cell adhesion molecule-1 and the unique shape-dependent electrical properties of the design, the local conductivity exhibits a rapid and sustained increase following systemic delivery, exceeding 2.39-fold the initial level within 2 h. EASP-assisted RFA demonstrates a significant enhancement in heat deposition, characterized by increased temperatures and expanded ablation zones in the diseased arteries. Notably, the 4 h accumulation group exhibited a 59.85% higher temperature increase and a 94.48% greater ablation area than the 2 h group. Through the integration of nanotechnology, this study provides a new approach to improving both the targeting precision and therapeutic efficiency of RFA-based atherosclerosis treatment.
