Jiangyue Wang, Xinrui Zheng, Xinghai Wang, Yiruo He, Xueling Xiao, Sa Cha, Wenjie Zhang, Ding Bai, Ye Tian
{"title":"Development of a gelatin methacryloyl double-layer membrane incorporated with nano-hydroxyapatite for guided bone regeneration.","authors":"Jiangyue Wang, Xinrui Zheng, Xinghai Wang, Yiruo He, Xueling Xiao, Sa Cha, Wenjie Zhang, Ding Bai, Ye Tian","doi":"10.1039/d5bm00610d","DOIUrl":"https://doi.org/10.1039/d5bm00610d","url":null,"abstract":"<p><p>Guided bone regeneration (GBR) is an effective technique for treating bone defects, with barrier membranes playing a critical role in preventing soft tissue invasion while supporting bone formation. However, conventional collagen GBR membranes have limitations, including poor mechanical strength, high swelling ratio, rapid biodegradation, and fragile structures. In this study, we developed a heterogeneous double-layer membrane with tunable physical, chemical, and biological properties, fabricated through simple photopolymerization and lyophilization of gelatin methacryloyl (GelMA) and nanohydroxyapatite (nHA). By adjusting the crosslinking time, methacrylation degree, and nHA concentration, the cryogels showed porous microstructures with different pore sizes ranging from 93 to 360 μm. Compressive mechanical testing, swelling measurements, and <i>in vitro</i>/<i>in vivo</i> biodegradation assays confirmed that the methacrylation of gelatin increased the compressive modulus to 29.02 MPa (<i>p</i> = 0.0002), reduced the swelling ratio to 714% (<i>p</i> = 0.002), and slowed the degradation rate to 41.2% after 48 hours (<i>p</i> = 0.002). Incorporating nHA further enhanced the mechanical properties and extended the degradation time. GelMA and nHA-GelMA cryogels exhibited excellent biocompatibility and promoted osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), particularly in the nHA-GelMA cryogel with large pore sizes. We selected a GelMA cryogel with the smallest pore size for optimal barrier function and an nHA-GelMA cryogel with the highest osteogenic potential to construct the double-layer GBR membrane. In a rat calvarial defect model, this novel membrane significantly enhanced bone regeneration, demonstrating markedly improved bone volume/tissue volume (BV/TV) and bone mineral density (BMD) compared to the control group (<i>p</i> = 0.0042 and <i>p</i> = 0.0088, respectively), with efficacy comparable to that of a commercial GBR membrane. These findings demonstrate the promising potential of this simple, tunable double-layer GelMA/nHA cryogel membrane as a superior alternative for GBR applications.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673391","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}
Justyna Swieton, Thu Thao Pham, Anna Gromotowicz-Poplawska, Krzysztof Szczubialka, Dariusz Pawlak, Andrzej Mogielnicki, Shin-Ichi Yusa, Bartlomiej Kalaska
{"title":"Evaluation of the anticoagulant activity and safety of PMPC-PSSS and PMPC-PVBTAC block copolymers.","authors":"Justyna Swieton, Thu Thao Pham, Anna Gromotowicz-Poplawska, Krzysztof Szczubialka, Dariusz Pawlak, Andrzej Mogielnicki, Shin-Ichi Yusa, Bartlomiej Kalaska","doi":"10.1039/d5bm00406c","DOIUrl":"https://doi.org/10.1039/d5bm00406c","url":null,"abstract":"<p><p>Unfractionated heparin (UFH) remains a widely used anticoagulant; however, its use is associated with several limitations, including an elevated risk of bleeding, the potential for heparin-induced thrombocytopenia, and the necessity for frequent monitoring. Alternative anticoagulants with a lower risk of adverse effects and more predictable pharmacokinetics are currently under investigation. This study evaluates the anticoagulant activity and safety of poly(2-methacryloyloxyethyl phosphorylcholine)-poly(sodium styrenesulfonate) (PMPC<sub>20</sub>-PSSS<sub><i>x</i></sub>, <i>x</i> = 83 and 198) anionic block copolymers and poly(2-methacryloyloxyethyl phosphorylcholine)-poly(vinylbenzyl trimethylammonium chloride) (PMPC<sub>20</sub>-PVBTAC<sub><i>y</i></sub>, <i>y</i> = 92 and 196) cationic block copolymers. PVBTAC-based cationic block copolymers exhibited stronger <i>in vitro</i> anticoagulant activity in whole blood than PSSS-based anionic block copolymers but caused adverse effects on blood cells. The PMPC<sub>20</sub>-PSSS<sub>83</sub> anionic block copolymer affected the <i>in vitro</i> activity of factors II, V, VIII, IX, X, and XII and exhibited potent anticoagulant effects in a rat model, without significant changes in haemolysis, platelet count, or cardiorespiratory parameters. Due to its high biocompatibility and strong anticoagulant effect, PMPC<sub>20</sub>-PSSS<sub>83</sub> is a promising candidate with notable therapeutic potential in clinical applications.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673392","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}
Grace Felciya Sekar Jeyakumar, Poornima Velswamy, Deebasuganya Gunasekaran, Alexandar Vincent Paulraj, Nivethitha Paneerselvam Manimegalai, Uma Tiruchirappalli Sivagnanam
{"title":"Injectable hybrid hydrogel-mediated calcium-sensing receptor (CaSR) activation for enhanced osteogenesis and bone remodeling.","authors":"Grace Felciya Sekar Jeyakumar, Poornima Velswamy, Deebasuganya Gunasekaran, Alexandar Vincent Paulraj, Nivethitha Paneerselvam Manimegalai, Uma Tiruchirappalli Sivagnanam","doi":"10.1039/d5bm00349k","DOIUrl":"https://doi.org/10.1039/d5bm00349k","url":null,"abstract":"<p><p>Injectable hydrogels have transfigured bone tissue engineering by offering minimally invasive solutions for treating irregularly shaped critical-size bone defects. Unlike traditional fixed-shaped bone grafts that require invasive surgeries and precise defect matching, injectable hydrogels adapt to defect geometries and accelerate healing. The hydrogels mimic the extracellular matrix with their porous, interconnected 3D architecture, promoting cell adhesion, proliferation, differentiation, vascularization, and nutrient flow, which are essential for effective bone regeneration and affirm the osteoconductivity. Chitosan-alginate hydrogels are particularly promising due to their mechanical stability, biodegradability, and ability to deliver bioactive compounds sustainably. To enhance its osteoinductive properties, bioinorganic ions such as strontium (Sr<sup>2+</sup>)-based hybrid nanocomposites have been explored. Strontium has garnered attention for its ability to activate the calcium-sensing receptor (CaSR)-mediated signaling pathways by regulating bone resorption and bone formation by various bone matrix proteins, thereby promoting bone homeostasis and regeneration. Strontium's ionic similarity to calcium enables it to act as a robust activator of CaSR, triggering pathways that enhance bone regeneration. Building on this, we developed an innovative hybrid material hydrogel by reinforcing the chitosan-alginate hydrogels with a Sr-Fe-TQ (strontium-iron-thymoquinone) nanocomposite. This bioengineered hydrogel system demonstrated excellent hemocompatibility (in human RBCs), cytocompatibility, biocompatibility, and enhanced efficiency <i>in vitro</i> in MG-63 osteoblast-like cells. <i>In vivo</i> studies using a rabbit critical-size defect model showed accelerated bone remodeling, achieving better defect closure and superior bone volume restoration (∼99%) compared to the controls. This study underscores the transformative potential of the Sr-Fe-TQ hydrogel as an injectable, osteoconductive, and osteoinductive scaffolds for critical-size defect repair. By combining minimally invasive delivery, sustained bioactive release, and superior regenerative outcomes, this hydrogel system addresses key challenges in bone tissue engineering, paving the way for next-generation biomaterials in regenerative medicine.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673394","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":"Multifunctional bilayer dressings: a next generation biomaterial for enhanced wound healing.","authors":"Dimpy Bhardwaj, Saurav Kumar, Garima Agrawal","doi":"10.1039/d5bm00095e","DOIUrl":"https://doi.org/10.1039/d5bm00095e","url":null,"abstract":"<p><p>Wound healing poses a considerable challenge in the healthcare sector, especially for chronic and infected wounds, requiring advanced technological alternatives that surpass conventional dressings. Bilayer dressings, which combine hydrogels and electrospun nanofibers together, have recently emerged as a next generation biomaterial that mimics skin to enhance wound healing. Herein, we first describe skin physiology and various steps that are involved in the wound healing process. Based on this foundation, we further describe advancements made in individual hydrogel and electrospun nanofiber based single layer wound dressings and their <i>in vivo</i> implications. We discuss the shortcomings of these single layer dressings, and highlight the potential of bilayer dressings in overcoming these issues. Furthermore, we comprehensively elaborate the efforts made so far to develop bilayer dressings to advance skin wound care treatment. Finally, we discuss the challenges and opportunities existing in the area of bilayer dressings that should be addressed to achieve their clinical application in future.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673395","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":"4D-printed multifunctional hydrogels as flexible strain sensors and nerve conduits.","authors":"Akshat Joshi, Saswat Choudhury, Arabinda Majhi, Sampath Parasuram, Vageesh Singh Baghel, Samrat Chauhan, Supriya Khanra, Debrupa Lahiri, Kaushik Chatterjee","doi":"10.1039/d5bm00166h","DOIUrl":"https://doi.org/10.1039/d5bm00166h","url":null,"abstract":"<p><p>Conductive hydrogels are critical for advanced bioelectronics and the repair of electroactive tissues. However, developing conductive hydrogels into complex biomimetic shapes with good flexibility and bioactivity poses a major biofabrication challenge. This study utilizes dual-component hydrogel inks based on alginate incorporating conductive fCNT (acid-functionalized carbon nanotube) nanofillers, with the composite gel exhibiting an electrical conductivity of 6.6 ± 0.5 mS cm<sup>-1</sup> at 2 mg ml<sup>-1</sup> fCNT loading. Owing to their good combination of electrical conductivity and mechanical properties, the (three-dimensional) 3D-printed gels were successfully applied as strain sensors to sense subtle human motions, such as finger and elbow bending. Bilayered hydrogels prepared through four-dimensional (4D) printing exhibited programmable shape changes owing to differential swelling post-printing to yield nerve guidance conduits (NGCs) of intricate and tissue-adaptable designs, such as single and multichannel and bifurcated designs, based on accurate prediction by finite element analysis. The proliferation of neural cells was enhanced on the fCNT-gel compared to the neat gel. Sutureless deployment and enhanced peripheral nerve regeneration were established for the fCNT-gel in a rat sciatic nerve injury model. Overall, this work presents the fabrication of 4D-printed multifunctional conductive hydrogels, which can find diverse applications ranging from implantable nerve conduits to strain sensing.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673389","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":"Functionalized cell membrane-coated nanoparticles induce local immune tolerance for durable survival of allogeneic islet grafts.","authors":"Yi-Qun Sun, Ying-Li Luo, Hui-Xiao Li, Zi-Lu Wang, Wen-Qi Xu, Zi-Dong Lu, Cong-Fei Xu","doi":"10.1039/d5bm00717h","DOIUrl":"https://doi.org/10.1039/d5bm00717h","url":null,"abstract":"<p><p>Allogeneic islet transplantation is a promising therapeutic strategy for type 1 diabetes (T1D). However, establishing durable immune tolerance to protect engrafted islets without systemic immunosuppression remains a major challenge. In this study, we develop functionalized cell membrane-coated nanoparticles to induce local immune tolerance and achieve long-term islet graft protection. These nanoparticles, termed FasL@Rapa NPs, are engineered by coating rapamycin-loaded polymeric cores with cell membranes expressing Fas ligand (FasL). Upon co-transplantation with allogeneic islets into the subrenal capsule of T1D mice, FasL@Rapa NPs promote apoptosis of autoreactive effector T cells <i>via</i> FasL-Fas interaction, and simultaneously expand the population of regulatory T cells <i>via</i> rapamycin-mediated immune regulation within the islet grafts. This dual immunomodulatory action successfully establishes local immune tolerance, enabling prolonged graft survival and sustained insulin secretion, thereby restoring normoglycemia in diabetic mice. This study presents a promising approach to prevent transplant rejection without the risks associated with systemic immunosuppression.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635685","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":"Lipid-based polymeric biomaterial-mediated <i>ex vivo</i> natural killer cell surface engineering.","authors":"Jaewon Park, Kyung Mu Noh, Kyobum Kim","doi":"10.1039/d5bm00692a","DOIUrl":"https://doi.org/10.1039/d5bm00692a","url":null,"abstract":"<p><p>Natural killer (NK) cell-based immunotherapy has gained significant attention due to its ability to selectively recognize and eliminate cancer cells through immunological synapse formation while sparing normal cells. However, the therapeutic efficacy of NK cells against solid tumors remains limited, primarily due to insufficient tumor-specific targeting ligands. Although chimeric antigen receptor (CAR)-engineered NK cell therapy has been developed to address this challenge, its clinical translation is hindered by challenges like high cost, low transfection efficiency, and concerns associated with genetic modification. As an alternative, biomaterial-based NK cell surface engineering has emerged as a promising strategy to enhance tumor-targeting capabilities, without altering the intrinsic properties of NK cells. In particular, lipid-based polymeric biomaterial platforms enable efficient ligand-receptor interactions, thereby enhancing NK cell-mediated tumor recognition and cytotoxicity. This review highlights recent advances in the lipid-based NK cell surface engineering platform, discussing its advantages over genetic modifications and its potential to improve the efficacy of NK cell-based cancer immunotherapy.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635686","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}
Suel-Kee Kim, Choong Kim, Hyo Won Moon, Ji You Han, Seong Woo Choi, So Hyang Park, Haeun Kim, Byung-Ok Choi, Ji Yoon Kang, Jong-Hoon Kim, Jong Hyun Kim
{"title":"Microencapsulation system for scalable differentiation of peripheral motor neurons from human induced pluripotent stem cells.","authors":"Suel-Kee Kim, Choong Kim, Hyo Won Moon, Ji You Han, Seong Woo Choi, So Hyang Park, Haeun Kim, Byung-Ok Choi, Ji Yoon Kang, Jong-Hoon Kim, Jong Hyun Kim","doi":"10.1039/d5bm00535c","DOIUrl":"https://doi.org/10.1039/d5bm00535c","url":null,"abstract":"<p><p>Stem cell-derived neural cells hold great potential for treating neurological disorders, but clinical translation is limited by the need for scalable, consistent, and functionally robust production systems. To address these challenges, we developed a microfluidic alginate encapsulation chip (MAEC) system for the high-throughput production of mature peripheral motor neurons from human induced pluripotent stem cells. Alginate was selected for its biocompatibility, low immunogenicity, and calcium-triggered gelation, enabling precise size control. Encapsulation conditions were optimized to produce uniform microcapsules, each containing a single embryoid body of defined size. A refined two-step purification strategy, combining on-chip mineral oil flushing and off-chip medium washing, efficiently removed cytotoxic oleic acid residues and significantly improved post-encapsulation cell viability. Encapsulated cells showed enhanced spontaneous differentiation capacity, and upon exposure to defined patterning cues, upregulated both early and terminal motor neuron markers. Extended cultures, both encapsulated and decapsulated, exhibited characteristic morphological and molecular features of mature motor neurons. Functional maturation was confirmed by whole-cell patch-clamp recordings, revealing repetitive spike firing and large-amplitude action potentials. The MAEC platform provides a scalable and immunoprotective system that supports stable encapsulation for transplantation and capsule-free release for downstream applications, enabling functionally relevant regenerative therapies and high-throughput drug screening and disease modeling.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635687","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}
Jinghang Li, Shuangyu Tian, Xi Zhang, Xinyang Deng, Haixing Xu, Lesan Yan
{"title":"Indocyanine green-based nanomedicine for theranostic applications.","authors":"Jinghang Li, Shuangyu Tian, Xi Zhang, Xinyang Deng, Haixing Xu, Lesan Yan","doi":"10.1039/d5bm00670h","DOIUrl":"https://doi.org/10.1039/d5bm00670h","url":null,"abstract":"<p><p>Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye approved by the FDA, is widely utilized in biomedical applications due to its excellent biocompatibility, photophysical properties, and versatility in imaging and therapeutic modalities. Despite its advantages, ICG's clinical use is limited by photothermal degradation, poor solution stability, rapid <i>in vivo</i> clearance, and low fluorescence quantum yield. To overcome these challenges, advanced nano-delivery systems, including lipid-based, polymer-based, protein-based, inorganic-based, and carrier-free formulations, have been developed to enhance ICG's stability, circulation time, and targeting efficiency. These nanoformulations enable multimodal applications, such as NIR fluorescence imaging, photoacoustic imaging, optical coherence tomography, two-photon fluorescence imaging, photothermal therapy (PTT), photodynamic therapy (PDT), and sonodynamic therapy (SDT), across various disease models, particularly in tumor diagnosis, image-guided surgery, lymph node mapping, inflammation, and cardiovascular diseases. This review highlights recent progress in ICG-based nanomedicines, emphasizing their design, diagnostic and therapeutic capabilities, and potential for clinical translation. By addressing ICG's limitations through nanotechnology, these systems offer promising strategies for precision medicine, with opportunities for further optimization to enhance therapeutic outcomes.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625023","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}
Hongfei Sun, Guifeng An, Sarula Bao, Wenbo Du, Ya Su, Dezhi Sun, Xiaohui Zhang
{"title":"Structure-optimized poly(α-amino acid)-based antimicrobial peptide mimetics with balanced bactericidal activity and biosafety for MRSA peritonitis therapy.","authors":"Hongfei Sun, Guifeng An, Sarula Bao, Wenbo Du, Ya Su, Dezhi Sun, Xiaohui Zhang","doi":"10.1039/d5bm00785b","DOIUrl":"https://doi.org/10.1039/d5bm00785b","url":null,"abstract":"<p><p>Developing novel antimicrobial peptide (AMP) mimetics is a crucial approach to addressing the growing problem of bacterial resistance by inheriting the antibacterial advantages of AMPs while overcoming their inherent limitations. However, improperly controlled positive charges and hydrophobic structures in AMP mimetics can lead to strong cytotoxicity. Therefore, achieving high antibacterial efficacy while maintaining favorable biocompatibility is a crucial challenge for AMP mimetics. Herein, based on poly-α-L-lysine (PLL), which possesses potential for biological applications, we introduced varying numbers of aryl side chains to prepare a series of poly (α-amino acids)-based AMP mimetics. Through structure-activity relationship (SAR) studies modulating the balance between positive charge and hydrophobic units, we identified PAA-1, which exhibits a favorable balance between antimicrobial activity and biocompatibility. <i>In vitro</i> antibacterial studies demonstrated that PAA-1 exhibits potent activity against drug-resistant bacteria and biofilm compared to vancomycin, with negligible toxicity. Mechanistic studies suggested that PAA-1 inherits the membrane-damaging mechanism of AMP and shows no drug resistance after 14 consecutive passages. <i>In vivo</i> studies indicated that PAA-1 exhibits superior therapeutic efficacy against <i>Methicillin-resistant Staphylococcus aureus</i> (MRSA)-induced peritonitis, providing greater survival protection compared to vancomycin, with a 7-day survival rate of 80% and demonstrating favorable biosafety. This study constructed AMP mimetics with a balanced antibacterial-biocompatibility profile by optimizing SAR. This provides a referable methodology for discovering more effective AMP mimetics and offers a preclinical research protocol for peritonitis treatment.</p>","PeriodicalId":65,"journal":{"name":"Biomaterials Science","volume":" ","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606884","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}