Journal of biomedical materials research. Part A最新文献

{"title":"Keratin Rich PCL Blended Nano-Microfibrous Sheet as a Bioactive Immunomodulatory ECM Analog Toward Dermal Wound Healing—In Vitro and In Vivo Responses","authors":"Krishna Dixit,&nbsp;Hema Bora,&nbsp;Gaurav Kulkarni,&nbsp;Nantu Dogra,&nbsp;Tamal Kanti Sengupta,&nbsp;Gayatri Mukherjee,&nbsp;Santanu Dhara","doi":"10.1002/jbm.a.37888","DOIUrl":"https://doi.org/10.1002/jbm.a.37888","url":null,"abstract":"<div>\u0000 \u0000 <p>Being an excretory scleroprotein, human hair-derived keratin with inherent bioactive peptide cues may actively participate in an immunomodulatory role in the wound microenvironment. In the current study, nano-microfibrous structural attributes mimicking the extracellular matrix were prepared using a polymer blend containing a high loading of keratin as a bioactive matrix by electrospinning, where polycaprolactone (PCL) was used as an electrospinnable aid. The FESEM analysis showed smooth fibers with diameters ranging from 100 to 220 nm. High keratin loading facilitated improved cellular affinity due to the presence of bioactive peptide cues. Physico-chemical characterization confirmed the presence of protein within the PCL matrix, and the modulus of the material (~25 MPa) was found to be similar to that of native skin. Furthermore, keratin-rich matrices evidenced the potential to modulate macrophages toward M2 macrophages. In vitro assessment with human dermal fibroblasts (HDFs) demonstrated enhanced cytocompatibility-like cellular activity and cell proliferation. In vivo studies evidenced the proactive role of the KPCL matrix in supporting full-thickness wound healing and balancing macrophage activity (CD68 and CD206 immunostaining). Immunohistochemistry and RT-PCR studies showed increased COLI and COLIII expression, evidencing dermal reconstruction within 18 days. Enhanced P63 and K14 expression supported the synergistic role of reepithelialization by the matrix enriched with keratin. Overall, the study showed that the keratin-based matrix facilitates skin wound healing.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571300","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":"Fabrication of 3D Hemispherical PCL-Based Scaffolds Through Far-Field Electrospinning Method for Their Potential Use as Contact Lenses","authors":"Hamed Hosseinian,&nbsp;Aida Rodriguez-Garcia,&nbsp;Samira Hosseini","doi":"10.1002/jbm.a.37874","DOIUrl":"https://doi.org/10.1002/jbm.a.37874","url":null,"abstract":"<div>\u0000 \u0000 <p>Maintaining precise control over fiber alignment during the electrospinning process is a significant challenge in material science. Various techniques have been explored to enhance fiber alignment, including the use of rotating collectors, patterned electrodes, and magnetic fields. However, these methods are typically complex, expensive, and involve multiple procedural steps, which can hinder their practical application in industrial settings. In this work, polycaprolactone (PCL) was used to electrospun scaffolds characterized by meshed, aligned, and grid fiber structures. A cost-effective approach for fabricating grid fibers, offering enhanced control over the scaffold, and potentially beneficial for medical applications was developed in this study. Using previously fabricated aligned fibers served as a foundation for developing ocular contact lenses incorporating the newly designed grid and meshed fibers. A comparative proof-of-concept study was conducted, utilizing three distinct fiber orientations to evaluate the efficacy and potential use in ocular drug delivery of each fiber type within the scaffolds. The morphology, light transmittance, mechanical properties, and wettability of the contact lenses were systematically assessed. The PCL-based ocular contact lenses, specifically tailored to conform to the anatomical shape of the eye, demonstrated a significant extension in Rhodamine B residence time, achieving an increase of up to two hours compared to conventional eye drops on the porcine cornea. Among the fiber types analyzed, grid fibers emerged as the most promising, followed by aligned fibers, both exhibiting superior Rhodamine B retention compared to meshed fibers. In conclusion, the innovative advancements in fiber alignment techniques and the use of PCL in the fabrication of ocular contact lenses underscore the potential for enhanced medical applications.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571394","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":"Pirfenidone Delivery by Blow-Molded PCL Nanofiber Mat to Reduce Collagen Synthesis by Fibroblasts","authors":"Maximilian Zernic,&nbsp;Maryo Kohen,&nbsp;Faruk H. Orge,&nbsp;Amel Ahmed,&nbsp;Ozan Akkus","doi":"10.1002/jbm.a.37884","DOIUrl":"https://doi.org/10.1002/jbm.a.37884","url":null,"abstract":"<p>Elevated intraocular pressure (IOP) during glaucoma is sometimes mitigated by insertion of glaucoma drainage devices (GDD). Excessive fibrosis around GDD plates may confine drainage and requiring revision surgeries in some patients. Pirfenidone (PFD) is an FDA approved drug to treat lung fibrosis, and it may be effective in limiting capsule formation around the GDD. To enable this, we aimed to develop a polymeric GDD encasement sheath that can sustainably release PFD to reduce fibrous capsule formation. The PFD-doped sheath was manufactured by blow molding of (poly)caprolactone (PCL). We investigated the effects of PCL concentration, spray distance, and molecular weight on the morphology of nanofibers as well as the release rate of PFD. The effects of PFD delivery on viability, number of living cells and collagen production by L-929 fibroblasts were measured in vitro. It was found that concentrations of 6%, 8%, and 10% PCL resulted in average fiber diameters of 277 ± 134, 436 ± 176, and 689 ± 297 nm, respectively. With increasing fiber diameter, the blow-spun nanofiber matrix displayed reduced burst release of PFD; ~75%, ~60%, and 45% respectively. Lower molecular weight PCL (25 kDa) demonstrated a slower release than higher molecular weight PCL (80 kDa). PCL loaded with PFD reduced collagen synthesis by L929 fibroblasts in vitro. The materials were also placed in a preliminary capacity as a proof of concept in the extraorbital space in rabbits and scored histologically to infer the severity of the inflammatory reaction. Assessment of in vivo response to blow-spun nanofibrous forms of PCL indicated a notably high inflammatory reaction to PCL. Therefore, while PFD can be integrated in PCL during blow-spinning and demonstrates antifibrotic effect in vitro, in vivo response to nanofibrous PCL by and itself suggests that this material platform does not appear to be suitable for drug delivery in the extraocular milieu.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37884","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533560","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":"Optimizing Tissue-Engineered Periosteum Biochemical Cues to Hasten Bone Allograft Healing","authors":"Alyson March,&nbsp;Hao Wu,&nbsp;Regine Choe,&nbsp;Danielle S. W. Benoit","doi":"10.1002/jbm.a.37890","DOIUrl":"https://doi.org/10.1002/jbm.a.37890","url":null,"abstract":"<div>\u0000 \u0000 <p>Although allografts remain the gold standard for treating critical-size bone defects, ~60% fail within 10 years of implantation. To emulate periosteum-mediated healing of live autografts, we have developed a tissue-engineered periosteum (TEP) to improve allograft healing. The TEP comprises cell-degradable poly(ethylene glycol) hydrogels encapsulating mouse mesenchymal stem cells and osteoprogenitor cells to mimic the periosteal cell population. Despite improvements in allograft healing, several limitations were observed using the TEP, specifically the modulation of host tissue infiltration and remodeling to support graft-localized vascular volume and callus bridging. Therefore, hydrogel biochemical cues were incorporated into TEP to enable cell–matrix interactions and remodeling critical for tissue infiltration. Adhesive peptide functionalization (RGD, YIGSR, and GFOGER) and enzymatic degradation rate (GPQGIWGQ, IPESLRAG, and VPLSLYSG) were screened using an in vitro 3D cell spheroid assay and design of experiments (DOE) to identify hydrogels that best supported tissue infiltration and integration. DOE analysis of various adhesive peptide combinations was used to optimize functionalization, revealing that individual RGD-functionalization and GFOGER-functionalization maximized in vitro cell infiltration. RGD and GFOGER hydrogels were then investigated in vivo as TEP (RGD-TEP and GFOGER-TEP, respectively) to evaluate the effect of hydrogel functionalization on TEP-mediated allograft healing in a murine femur defect model. RGD- and GFOGER-TEP promoted bone graft healing, with both groups exhibiting a 1.9-fold increase in bone callus volume over unmodified allografts at 3 weeks post-implantation. RGD-TEP promoted more significant bone tissue development, but GFOGER-TEP promoted greater torsional biomechanics over time. The few differences observed between TEP groups suggest hydrogel functionalization has a limited effect on TEP-mediated healing, with cell delivery via the TEP enough to improve bone regeneration. Future studies aim to investigate additional adhesive peptides with diverse combinations to identify potential synergies between adhesive peptides to promote TEP-mediated bone allograft healing.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533465","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":"Measurement and Comparison of Hyaluronic Acid Hydrogel Mechanics Across Length Scales","authors":"Aina Solsona-Pujol,&nbsp;Nikolas Di Caprio,&nbsp;Hannah M. Zlotnick,&nbsp;Matthew D. Davidson,&nbsp;Morgan B. Riffe,&nbsp;Jason A. Burdick","doi":"10.1002/jbm.a.37889","DOIUrl":"https://doi.org/10.1002/jbm.a.37889","url":null,"abstract":"<div>\u0000 \u0000 <p>Hydrogels are an important class of biomaterials that are being developed for use in medicine, such as in drug delivery and tissue engineering applications. To improve properties (e.g., injectability, nutrient transport, cell invasion), hydrogels are often processed as hydrogel microparticles (microgels) that can be used as suspensions or jammed into granular hydrogels. The mechanical properties of microgels are important across length scales, from macroscale bulk properties of granular assemblies to microscale interactions with cells; however, microgel mechanics are rarely reported due to challenges in their measurement. To address this, we report here a cost-effective, easy-to-use do-it-yourself (DIY) active feedback micropipette aspiration device to quantify the mechanics of individual microgels. Using norbornene-modified hyaluronic acid (NorHA) synthesized via an environmentally friendly, aqueous reaction as an exemplary hydrogel, we compare hydrogel mechanics across scales at various macromer concentrations. Hydrogels tested via uniaxial compression exhibit similar moduli values, trends of increasing modulus with increasing macromer concentration, and mechanical stability over time to the same formulations processed as microgels via batch emulsions (~170 μm) and tested via micropipette aspiration. Moduli range from ~50 to ~100 kPa as the NorHA macromer concentration increases from 3 wt% to 5 wt%. These findings are validated by testing with spherical nanoindentation, with similar moduli measured. Collectively, this work provides an accessible device that allows for the rapid testing of microgel mechanical properties, while also improving our understanding of hydrogel mechanics across scales for use in the design of microgels for biomedical applications.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533464","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":"Layer-By-Layer Functionalized Gauze With Designed α-Sheet Peptides Inhibits E. coli and S. aureus Biofilm Formation","authors":"Sarah E. Nick,&nbsp;James D. Bryers,&nbsp;Valerie Daggett","doi":"10.1002/jbm.a.37879","DOIUrl":"https://doi.org/10.1002/jbm.a.37879","url":null,"abstract":"<div>\u0000 \u0000 <p>Microbial biofilms on wounds lead to longer hospital stays, mechanical debridement, and higher mortality. Amyloid fibrils stabilize the bacterial biofilm's extracellular matrix (ECM) and represent a potential anti-biofilm target. As previously reported, <i>de novo</i> α-sheet peptides inhibit amyloid fibrillization and reduce biofilm formation in several bacterial species. Alginate (ALG) and chitosan (CH) are widely used in wound dressings due to their adhesive and antimicrobial activity. Here, we describe a layer-by-layer (LbL) functionalized gauze with alternating layers of ALG and CH loaded with α-sheet peptides for controlled release and biofilm inhibition at a wound site. Material analysis indicated successful LbL polyelectrolyte deposition and peptide incorporation. The LbL gauze facilitated controlled peptide release for 72 h with an initial burst delivery and demonstrated good biocompatibility with no toxicity towards human fibroblasts. The LbL gauze was assessed against <i>Escherichia coli</i> biofilms and reduced colony forming units (CFUs) of adherent bacteria by 81% and 96% as compared to the plain gauze for non-antibiotic and antibiotic (+gentamicin) conditions, respectively. A similar reduction in biofilm formation and increase in antibiotic susceptibility was observed for tests with <i>Staphylococcus aureus</i> and vancomycin. Thus, LbL gauze with incorporated α-sheet peptides demonstrated anti-biofilm properties for both gram-negative and gram-positive bacteria and presents an alternative wound dressing for the prevention of biofilm-associated infections.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533466","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":"3D Bioprinting Inner Ear Organ of Corti Organoids Induce Hair Cell Regeneration","authors":"Yingjie Wang,&nbsp;Haobo Li,&nbsp;Junming Zhang,&nbsp;Mengyu Chen,&nbsp;Yiyin Pan,&nbsp;Xiangxin Lou","doi":"10.1002/jbm.a.37892","DOIUrl":"https://doi.org/10.1002/jbm.a.37892","url":null,"abstract":"<div>\u0000 \u0000 <p>Hearing loss is often regarded as “invisible disability” which seriously affects the quality of life. The majority of hearing loss cases are caused by the damage to inner ear hair cells or connected spiral ganglion cells, and there is a lack of effective treatment measures. In recent years, significant progress has been made in the use of two-dimensional (2D) culture systems to induce the regeneration of auditory cells. However, the regenerated hair cells cannot form effective functional ciliary bundles under the 2D system, let alone establish synaptic contact with spiral ganglion cells, so they cannot truly achieve physiological repair of hearing. In this study, our aim is to construct a three-dimensional (3D) organ of Corti organoid through 3D bioprinting, which combines “3D culture scaffold + multiple induction signals + inner ear stem cells.” Then we evaluate the effects of the organoids on the differentiation of inner ear stem cells into auditory cells. We found that the organoids promoted adhesion and growth of inner ear stem cells, as well as the production of hair cells and nerve cells. The research may develop a novel approach for studying auditory cell regeneration and hearing loss repair.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533467","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":"Recent Updates on Blood Purification: Use of Smart Polymer Materials","authors":"Can Ergun,&nbsp;Hakan Eskizengin","doi":"10.1002/jbm.a.37883","DOIUrl":"https://doi.org/10.1002/jbm.a.37883","url":null,"abstract":"<div>\u0000 \u0000 <p>Blood purification is indispensable in addressing various conditions such as liver dysfunction, autoimmune diseases, and renal failure whereby toxins have to be cleared from the bloodstream effectively. Conventional methods that involve hemoperfusion, hemodialysis, and hemofiltration possess several weaknesses, including loss of plasma components and inefficient clearance of high molecular weight solutes. This review explores current developments in blood purification techniques particularly stimuli-responsive polymers for use in extracorporeal therapy among other applications. Many aspects of engineering stimuli-responsive polymers are described in terms of their role in the removal of small soluble molecules and toxins in blood purification techniques. The development of stimuli-responsive systems has introduced a new paradigm in blood purification by enabling selective, on-demand control of polymer parameters in response to external stimuli such as temperature, pH, electrolytes, and light. Such advanced materials have been demonstrated potential for toxin clearance, minimizing thrombosis, and improving blood compatibility and antifouling, which are far much better than traditional approaches. Furthermore, the review presents a perspective on stimuli-responsive polymers that could be used in developing novel extracorporeal systems for future medical purposes.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481530","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":"Secreted Cytokines From Inflammatory Macrophages Modulate Sex Differences in Valvular Interstitial Cells on Hydrogel Biomaterials","authors":"Nicole E. Félix Vélez,&nbsp;Kristi Tu,&nbsp;Peng Guo,&nbsp;Ryan R. Reeves,&nbsp;Brian A. Aguado","doi":"10.1002/jbm.a.37885","DOIUrl":"https://doi.org/10.1002/jbm.a.37885","url":null,"abstract":"<p>Patients with aortic valve stenosis (AVS) experience fibrosis and/or calcification in valve tissue, which leads to heart failure if left untreated. Inflammation is a hallmark of AVS, and secreted cytokines from pro-inflammatory macrophages are thought to contribute to valve fibro-calcification by driving the activation of valvular interstitial cells (VICs) to myofibroblasts. However, the molecular mechanisms by which inflammatory cytokines differentially regulate myofibroblast activation as a function of biological sex are not fully defined. Here, we developed an in vitro hydrogel culture platform to culture male and female valvular interstitial cells (VICs) and characterize the sex-specific effects of inflammatory cytokines on VIC activation to myofibroblasts and osteoblast-like cells. Our data reveal that tumor necrosis factor alpha (TNF-α) modulates female-specific myofibroblast activation via MAPK/ERK signaling, nuclear chromatin availability, and osteoblast-like differentiation via RUNX2 nuclear localization. In parallel, our data also suggest that male-specific myofibroblast deactivation in response to TNF-α occurs via alternative pathways outside of MAPK/ERK signaling. Collectively, hydrogel biomaterials as cell culture platforms are critical for distinguishing sex differences in cellular phenotypes.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37885","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481407","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":"Enhanced Anticancer Effects Through Combined Therapeutic Model of Macrophage Polarization and Cancer Cell Apoptosis by Multifunctional Lipid Nanocomposites","authors":"Kamonlatth Rodponthukwaji,&nbsp;Ladawan Khowawisetsut,&nbsp;Nathachit Limjunyawong,&nbsp;Natsuda Kunwong,&nbsp;Kongpop Duangchan,&nbsp;Sirinapa Sripinitchai,&nbsp;Sith Sathornsumetee,&nbsp;Tam Nguyen,&nbsp;Chatchawan Srisawat,&nbsp;Primana Punnakitikashem","doi":"10.1002/jbm.a.37886","DOIUrl":"https://doi.org/10.1002/jbm.a.37886","url":null,"abstract":"<p>Although the mono-anticancer therapy approach particularly directly targeting tumors is still common, this conventional method is generally deemed not effective and insufficient. In tumor microenvironment (TME), tumor-associated macrophages (TAMs, referred to as M2-polarized) play a crucial role in creating an immunosuppressive TME, contributing to various pro-tumorigenic effects. A promising strategy to inhibit tumor growth involves re-educating M2 macrophages into tumoricidal macrophages (M1). Therefore, combining macrophage reprogramming with cancer cell death induction in a single modality may offer synergistic benefits in cancer therapy. Here, we engineered a lipid-based delivery platform capable of co-delivering resiquimod (R848) and polyinosinic: polycytidylic acid (PIC). R848 in our nanosystem effectively triggered M2-to-M1 repolarization, as evidenced by the upregulation of M1 marker genes (<i>TNF</i>, <i>IL6</i>), the release of proinflammatory cytokines (TNF-α and IL-6), and the downregulation of the M2 marker gene, <i>MRC1</i>. On the other hand, the presence of PIC increased caspase-3/7 activity leading to cancer cell death through the apoptotic pathway. This nanocarrier system established a multifunctional platform to enhance the anticancer effect. The synergistic effect of repolarized macrophages in combination with the induction of apoptosis, facilitated by our nanomedicine, was evident in a co-culture system of macrophage and cancer cells, showing a significant increase in cancer cell death compared to individual treatments. These findings attractively demonstrated the potential of our multifunctional lipid nanoparticles as therapeutic agents for anticancer treatment by modulating the tumor immune microenvironment and simultaneously increasing cancer cell cytotoxicity.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37886","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447071","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}