Journal of biomedical materials research. Part A最新文献

{"title":"Performance Evaluation of Highly Uniform Astragalus Polysaccharide/Silk Fibroin Microspheres Fabricated via Microfluidics as Biodegradable Fillers: Collagen Regeneration and Tissue Reaction","authors":"Enshun Yang,&nbsp;Die Xie,&nbsp;Zongzhi Luo,&nbsp;Xin Che,&nbsp;Lihong Wang","doi":"10.1002/jbm.a.70122","DOIUrl":"10.1002/jbm.a.70122","url":null,"abstract":"<div>\u0000 \u0000 <p>Skin aging results from the synergistic assault of extrinsic environmental factors and intrinsic biological processes. While traditional microsphere implants promote skin rejuvenation through collagen regeneration, their clinical utility is hampered by non-biodegradability and risks such as granuloma formation. To overcome these limitations, this study employed microfluidic technology to develop highly uniform, novel injectable, highly bioactive, and degradable Astragalus polysaccharide/silk fibroin (APS/SF) composite microspheres for subcutaneous filling to promote collagen regeneration. We performed 3D simulations of droplet formation in a microfluidic chip using ANSYS Fluent to visualize the process. Experimental results indicated that these microspheres exhibited unprecedented uniformity (CV = 4.22% &lt; 5.00%) and circularity (0.90 ± 0.01), and degraded effectively in phosphate-buffered saline solutions. Furthermore, the microspheres demonstrated excellent biocompatibility and blood compatibility. In vitro experiments confirmed their ability to significantly promote the proliferation and migration of L929 fibroblasts. In vivo animal studies further indicated that implanted microspheres effectively induced collagen regeneration. Collectively, this research highlighted the significant therapeutic potential of APS/SF microspheres as an innovative and safe biomaterial for skin rejuvenation.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive-Loaded Detachable Crosslinked Hyaluronic Acid Microneedles: Structural Validation and Clinical Anti-Wrinkle Efficacy","authors":"Puttikorn Pukfukdee,&nbsp;Supanan Ampawa,&nbsp;Wirada Littirak,&nbsp;Supakij Suttiruengwong,&nbsp;Pravit Asawanonda,&nbsp;Supason Wanichwecharungruang","doi":"10.1002/jbm.a.70113","DOIUrl":"10.1002/jbm.a.70113","url":null,"abstract":"<div>\u0000 \u0000 <p>Delivering a persistent biopolymer matrix to the superficial dermis remains a significant challenge for microneedle systems due to the inherent limitations of conventional dissolving platforms. Here, we present a detachable microneedle design that permits rapid needle separation during administration. To biologically compensate for the relatively short 350 μm needle geometry designed for at-home safety, this system utilizes a crosslinked hyaluronic acid (cHA) matrix loaded with cosmetic peptides and functional excipients. The primary objective is to reliably deliver this composite biochemical cHA matrix into the skin to a depth of ~300 μm, which corresponds to the dermal–epidermal junction. Segmented mechanical compression analysis revealed that the non-polymeric payload did not compromise the matrix; rather, it significantly improved the initial axial stiffness from 0.059 ± 0.004 to 0.081 ± 0.005 N/mm per needle. This structural enhancement minimized axial displacement under load, enabling the 350 μm needles to reliably reach an ex vivo penetration depth of 335 ± 22 μm. A 14-day clinical evaluation (<i>n</i> = 28) using three-dimensional topography demonstrated excellent clinical tolerability with no adverse effects and significant reductions in surface roughness (<i>R</i>_<i>a</i>) and maximum wrinkle height (<i>R</i>_<i>t</i>) both immediately and at the conclusion of treatment.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining Supramolecular and Covalent Chemistry to Form Reinforced Fibrillar Network Hydrogels From Fibrinogen Derivatives","authors":"Noa Notea-Debutton,&nbsp;Haneen Simaan-Yameen,&nbsp;Dror Seliktar","doi":"10.1002/jbm.a.70117","DOIUrl":"10.1002/jbm.a.70117","url":null,"abstract":"<p>Fibrin hydrogels provide a highly supportive environment for three-dimensional cell growth and morphogenesis but are limited by insufficient stability to maintain their shape and mechanical integrity. To address this limitation, we developed a reinforced fibrin hydrogel incorporating photo-crosslinked methacrylated fibrinogen (FibMA). These interpenetrating polymer network (IPN) hydrogels were formed by thrombin-mediated activation of fibrinogen to initiate supramolecular fibrin assembly (fibrillogenesis), followed by light-activated covalent crosslinking of FibMA (photopolymerization). The unique interaction between the supramolecular and covalent chemistries, in tandem, resulted in a reinforced fibrillar network (RFN) architecture with exceptional control over mechanical properties. Precise control over the dynamic viscoelastic moduli of the FibMA–fibrin IPN hydrogel (FibMAtrx) was achieved by delaying the initiation of the photochemistry, thereby increasing the thrombin reaction time (TRT). Following covalent crosslinking, FibMAtrx exhibited more than a fivefold increase in dynamic viscoelastic moduli, depending on TRT and hydrogel composition. Fibroblasts encapsulated within FibMAtrx IPNs exhibited high viability and extensive morphogenesis, with quantitative cell spreading governed primarily by FibMA content rather than hydrogel stiffness. Cell-mediated hydrogel shrinkage after 1 week of culture (i.e., compaction) was substantially reduced in FibMAtrx IPNs, whereas fibrin single-network hydrogels compacted to a fraction of their original size. Together, these findings demonstrate the potential of proteinaceous reinforced fibrillar IPN hydrogels derived from fibrinogen and FibMA to support cell growth, enable tunable viscoelastic properties, resist compaction and enzymatic degradation, and maintain shape integrity in cell-laden fibrillar protein hydrogels.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Evaluation of Polyvinyl Alcohol/Carboxymethyl Chitosan Hydrocolloid Incorporating Cynodon dactylon Extract and Zinc Oxide Nanoparticle for Bedsore Healing in a Wistar Rat Model","authors":"Sahar Molzemi,&nbsp;Sepehr Zamani,&nbsp;Maryam Molaei,&nbsp;Naimeh Mahheidari,&nbsp;Mehdi Naeiji,&nbsp;Milad Rezvani,&nbsp;Saeed Haghi-Daredeh,&nbsp;Majid Salehi","doi":"10.1002/jbm.a.70115","DOIUrl":"https://doi.org/10.1002/jbm.a.70115","url":null,"abstract":"<div>\u0000 \u0000 <p>Pressure ulcers present a serious clinical challenge due to their impaired healing processes and increased risk of infection, particularly for immobilized patients. This study aims to address the need for advanced wound dressings by developing a multifunctional polymeric hydrocolloid/film that blends zinc oxide (ZnO) nanoparticles, <i>Cynodon dactylon</i> extract, polyvinyl alcohol (PVA), and carboxymethyl chitosan (CMC). Composite hydrocolloids were fabricated via solvent casting and subsequently cross-linked with SA. We made four different formulations: pure CMC-PVA (H₁), CMC-PVA/ZnO (H₂), and CMC-PVA/<i>C. dactylon</i> (H₃), and CMC-PVA/<i>C. dactylon</i>/ZnO (H₄). The hydrocolloids were characterized using SEM, FTIR, and DLS, and their hemocompatibility, porosity, biodegradation, swelling, blood uptake, cell viability (MTT assay), potential anti-inflammatory-related effects based on protein denaturation inhibition, and in vitro release were all tested. The in vivo efficacy was assessed utilizing a Wistar rat model for pressure ulcers over a 14-day duration, incorporating histological examinations of the healed tissues. The H₄ hydrocolloid had the best microstructure, was very porous (about 70%), broke down in a controlled way, and absorbed fluids very well. FTIR analysis confirmed that bioactive components were successfully added through hydrogen bonding and coordination interactions. The H₄ formulation showed satisfactory hemocompatibility (&lt; 4% hemolysis), increased fibroblast growth (112% viability at 72 h), and combined anti-inflammatory effects. The H₄ hydrocolloid closed about 91% of the wounds in vivo, and it did a better job of epithelialization, collagen deposition, and reducing inflammation than the control groups. The CMC-PVA/<i>C. dactylon</i>/ZnO composite hydrocolloid demonstrates significant potential as a multifunctional wound dressing for the treatment of pressure ulcers, leveraging the synergistic effects of natural extracts and nanoparticles to promote expedited and structured tissue regeneration.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148324932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Bone-Targeted LNP Delivery of Anti-Sclerostin Antibody mRNA for the Treatment of Osteoporosis","authors":"Pengcheng Ren,&nbsp;Diaodiao Wang,&nbsp;Wenqiang Sun,&nbsp;Danning Li,&nbsp;Sidong Yang,&nbsp;Shudong Zhang,&nbsp;Yiquan Zhang,&nbsp;Yubo Liu,&nbsp;Peng Hu,&nbsp;Jiaxin Li,&nbsp;Qi Yao","doi":"10.1002/jbm.a.70103","DOIUrl":"10.1002/jbm.a.70103","url":null,"abstract":"<p>Messenger RNA (mRNA) therapy represents a transformative platform in regenerative medicine, but its application to skeletal disorders remains limited by the pronounced hepatic tropism of conventional lipid nanoparticle (LNP) delivery systems. To redirect the distribution of biomolecules to bone tissue, we developed a bone-targeting mRNA nanocarrier (SA@LNP-D) through microfluidic synthesis followed by surface conjugation of the Asp8 peptide (binding to hydroxyapatite). This system enables efficient expression of anti-sclerostin antibody mRNA in bone tissue, thereby achieving therapeutic effects for osteoporosis treatment. Our in vitro experimental results have demonstrated that LNP modified with bone-targeting peptides exhibits significant bone affinity and can efficiently bind to hydroxyapatite and isolated bone. Furthermore, the in vivo results confirmed that SA@LNP-D effectively reduces hepatic sequestration and specifically accumulates in bones through mineral-directed anchoring. In a murine ovariectomy model of osteoporosis, systemic delivery of bone-targeted LNP demonstrated a stronger therapeutic effect compared to conventional LNP. It not only stimulated bone formation but also inhibited bone resorption, thereby significantly restoring trabecular bone mass and microstructure. Together, this work establishes a targeted, nonhepatic mRNA delivery strategy that offers a safe and effective therapeutic option for osteoporosis and related skeletal conditions.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148311098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substrate Stiffness and Viscoelasticity Influence Fibroblast Senescence","authors":"Mackenzie L. Skelton,&nbsp;Tanvi Bhat,&nbsp;Ethan Yu,&nbsp;Afia Ofori,&nbsp;Steven R. Caliari","doi":"10.1002/jbm.a.70111","DOIUrl":"10.1002/jbm.a.70111","url":null,"abstract":"<p>Senescent cell accumulation has been implicated in aging and fibrotic disease, which are both characterized by increased tissue stiffness. However, the direct connection between tissue mechanics and senescence induction remains disputed in the literature. Thus, this work investigates the influence of hydrogel stiffness and viscoelasticity in promoting fibroblast senescence directly and in combination with genotoxic stress. We show that while lung fibroblast YAP/TAZ signaling declines with senescence induction, senescent fibroblasts maintain their mechanosensing capabilities with increased YAP/TAZ nuclear localization on higher stiffness hydrogels. Most notably, we find a unique role for hydrogel viscoelasticity in senescence induction, with soft (2 kPa) viscoelastic substrates promoting both the onset and amplification of senescence, even in the absence of genotoxic stress. These changes are not associated with a decline in YAP/TAZ activity, but instead with a decline in nuclear DAPI intensity, suggesting a role of nuclear organization in driving this phenotype. Overall, this work highlights the influence of mechanics, and viscoelasticity in particular, on the induction of fibroblast senescence.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148311103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Ethyl Cellulose–Ethanol Ablation in a Human-Sized 3D Construct of High-Grade Cervical Dysplasia","authors":"Gatha Adhikari,&nbsp;Alina Sharma,&nbsp;Kaitlin C. Fogg,&nbsp;Jenna L. Mueller","doi":"10.1002/jbm.a.70110","DOIUrl":"https://doi.org/10.1002/jbm.a.70110","url":null,"abstract":"<p>Current preclinical models for cervical dysplasia rely on animal systems that poorly mimic human anatomy. To address this and align with emerging initiatives to reduce animal experimentation, we developed a human-sized, 3D in vitro model of high-grade cervical dysplasia. The construct integrates normal human fibroblasts, keratinocytes, and SiHa cancer cells within a gelatin methacrylate (GelMA) hydrogel, engineered with a cervical “os” and asymmetric lesion to replicate native human cervical architecture. We utilized this platform to evaluate the efficacy and safety of ethyl cellulose–ethanol (EC–ethanol), a novel ablation therapy designed to mitigate the off-target leakage associated with traditional ethanol injections. While control injections of pure ethanol resulted in widespread, non-specific necrosis (approximately 99% cell death), EC–ethanol successfully formed a localized gel depot. High-resolution mapping of the ablation zone demonstrated that EC–ethanol significantly concentrated cytotoxicity within the dysplastic lesion while preserving surrounding healthy tissue. Margin analysis revealed a sharp therapeutic gradient, with cell death normalizing to background levels within approximately 2 mm of the injection site. These findings validate the translational potential of EC–ethanol as a spatially precise intervention and demonstrate the utility of macro-scale 3D models as powerful, ethical alternatives to animal testing for optimizing local drug delivery.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomaterial-Focused Strategies Targeting Dendritic Cells for Autoimmune Disease Treatment","authors":"Aiswarya Venkata Suresh Kumar,&nbsp;Julia Babensee","doi":"10.1002/jbm.a.70107","DOIUrl":"https://doi.org/10.1002/jbm.a.70107","url":null,"abstract":"<div>\u0000 \u0000 <p>Autoimmune diseases encompass over 100 distinct diseases where the immune cells betray our body by attacking the tissues they are meant to protect. Even though rare, 15 million Americans are collectively affected by autoimmune diseases, a number that continues to rise every year. Current treatment modalities primarily focus on alleviating symptoms rather than providing prevention or a cure. Tolerogenic dendritic cells (tolDCs) have gained popularity for autoimmune disease treatment as an alternative to traditional systemic immunosuppressive therapies due to their ability to restore immune homeostasis. However, clinical translation of tolDC therapies faces significant hurdles once injected into the body due to suboptimal delivery routes, systemic distribution throughout the body, faster clearance rate, phenotypic instability, and inefficient homing. So, the big question here is: How can we retrain dendritic cells to restore the immune balance while overcoming these challenges? Engineered biomaterials such as nanoparticles, microparticles, hydrogels, and polymer scaffolds offer innovative solutions by enabling targeted delivery of ex vivo-generated tolDCs or in situ reprogramming of endogenous dendritic cells (DCs) by delivering drugs and other bioactive agents at strategic locations. These platforms provide tunable release kinetics, enhanced targeting specificity, improved safety profiles, and high potency, highlighting their importance as a promising alternative to conventional administration methods. Biomaterials can modulate immune responses from inflammatory immune activation to immune tolerance, which is essential for long-term disease management. This review highlights recent advances in biomaterial-based delivery systems for DC delivery and their potential to redefine therapeutic strategies for autoimmune diseases.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Pro-Osteogenic Poly(l-Lactide-co-ε-caprolactone) Sponges Through Carbonate Apatite Integration","authors":"Zhanrui Lou,&nbsp;Ryo Kishida,&nbsp;Akira Tsuchiya,&nbsp;Kunio Ishikawa","doi":"10.1002/jbm.a.70112","DOIUrl":"https://doi.org/10.1002/jbm.a.70112","url":null,"abstract":"<div>\u0000 \u0000 <p>Flexible and porous sponges with high osteoconductivity have a wide range of bone healing applications. Although polymer/ceramic composite materials can serve as soft bone grafts, osteogenesis can be compromised when the ceramic surface is covered by the polymer. This study aimed to fabricate a bone-graft sponge with high elasticity and osteoconductivity by integrating carbonate apatite (CAp) particles inside and on the surface of poly(<span>l</span>-lactide-<i>co</i>-ε-caprolactone) (PLCL). A slurry comprising PLCL and a calcium carbonate (CaCO₃) precursor was freeze-dried to obtain a PLCL/CaCO₃ sponge, which was then phosphatized into a PLCL/CAp sponge using a mildly alkaline sodium phosphate solution. This sodium phosphate solution not only converted CaCO₃ into CAp but also partially degraded the PLCL matrix to expose CAp on the surface, which improved the hydrophilicity of the surface. Interconnected macropores with diameters of 500–600 μm were also introduced by embedding and subsequently leaching sodium chloride (NaCl) crystals from the PLCL/CaCO₃ sponge. In vitro cell experiments demonstrated that CAp and the macroporous structure significantly enhanced osteoblast adhesion and differentiation. In vivo evaluations using a rabbit femoral defect model revealed that CAp endowed the PLCL sponge with osteoconductivity, facilitating bone ingrowth from the defect margins in 4 weeks. The macroporous structure enabled bone regeneration throughout the sponge. These findings suggest that the developed PLCL/CAp sponge is a promising biomaterial for bone regenerative applications.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 7","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced Hypotonic Exposure and Sequential Membrane Cholesterol Enrichment Limit Phosphatidylserine Externalization and Enhance Circulatory Retention of Erythrocyte-Derived Microparticles","authors":"Shamima Zaman,&nbsp;Grant Swajian,&nbsp;Shiril Bhardwaj Iragavarapu,&nbsp;Md Tashdid Hossain Shoudho,&nbsp;Bahman Anvari","doi":"10.1002/jbm.a.70109","DOIUrl":"10.1002/jbm.a.70109","url":null,"abstract":"<p>Erythrocyte-derived carriers have emerged as effective biomimetic platforms for the delivery of therapeutic and imaging cargos. However, clearance by the mononuclear phagocytic system (MPS) limits their utility. Towards development of standardized methods for increased bioavailability, we have developed an approach that lowers the externalization of phosphatidylserine (PS), a biomarker for MPS clearance, to the outer leaflet of the membrane. Specifically, this approach minimizes the hypotonic treatment of erythrocytes to a single cycle for depleting the hemoglobin while enriching the membrane bilayer with cholesterol during depletion, and in the subsequent cargo loading step, using indocyanine green (ICG), a fluorescent probe as an illustrative cargo. Using this strategy, PS externalization remains limited to ~16% and 9% of the carrier system with and without the encapsulated ICG, respectively, compared to ~46%–99% following multiple hypotonic cycles without cholesterol enrichment. Carriers engineered using this method exhibit significantly reduced macrophage uptake in vitro. In vivo biodistribution studies in healthy mice show ~2.7-fold increase in blood-associated fluorescence, and ~3.3-fold decrease in splenic accumulation after intravascular injection relative to carriers formed by multiple cycles of hypotonic treatment and without cholesterol enrichment. This method provides an effective approach to improve the circulatory retention of erythrocyte-based carriers.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"114 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148255127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}