{"title":"The Application Progress of Nonthermal Plasma Technology in the Modification of Bone Implant Materials.","authors":"Chengbiao Ding, Hao Lv, Suoni Huang, Mengxuan Hu, Yanxinyue Liao, Xinyue Meng, Ming Gao, Hemu Chen, Xiaojun Feng, Zhengwei Wu","doi":"10.1021/acsbiomaterials.4c00081","DOIUrl":"10.1021/acsbiomaterials.4c00081","url":null,"abstract":"<p><p>With the accelerating trend of global aging, bone damage caused by orthopedic diseases, such as osteoporosis and fractures, has become a shared international event. Traffic accidents, high-altitude falls, and other incidents are increasing daily, and the demand for bone implant treatment is also growing. Although extensive research has been conducted in the past decade to develop medical implants for bone regeneration and healing of body tissues, due to their low biocompatibility, weak bone integration ability, and high postoperative infection rates, pure titanium alloys, such as Ti-6A1-4V and Ti-6A1-7Nb, although widely used in clinical practice, have poor induction of phosphate deposition and wear resistance, and Ti-Zr alloy exhibits a lack of mechanical stability and processing complexity. In contrast, the Ti-Ni alloy exhibits toxicity and low thermal conductivity. Nonthermal plasma (NTP) has aroused widespread interest in synthesizing and modifying implanted materials. More and more researchers are using plasma to modify target catalysts such as changing the dispersion of active sites, adjusting electronic properties, enhancing metal carrier interactions, and changing their morphology. NTP provides an alternative option for catalysts in the modification processes of oxidation, reduction, etching, coating, and doping, especially for materials that cannot tolerate thermodynamic or thermosensitive reactions. This review will focus on applying NTP technology in bone implant material modification and analyze the overall performance of three common types of bone implant materials, including metals, ceramics, and polymers. The challenges faced by NTP material modification are also discussed.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Klaudia Kaniewska, Marcin Mackiewicz, Oleh Smutok, Mykhailo Gonchar, Evgeny Katz, Marcin Karbarz
{"title":"Enzymatically Triggered Drug Release from Microgels Controlled by Glucose Concentration.","authors":"Klaudia Kaniewska, Marcin Mackiewicz, Oleh Smutok, Mykhailo Gonchar, Evgeny Katz, Marcin Karbarz","doi":"10.1021/acsbiomaterials.4c01721","DOIUrl":"10.1021/acsbiomaterials.4c01721","url":null,"abstract":"<p><p>This study aims to design microgels for controlled drug release via enzymatically generated pH changes in the presence of glucose. Modern medicine is focused on developing smart delivery systems with controlled release capabilities. In response to this demand, we present the synthesis, characterization, and enzymatically triggered drug release behavior of microgels based on poly(acrylic acid) modified with glucose oxidase (GOx) (p(AA-BIS)-GOx). TEM images revealed that the sizes of air-dried p(AA-BIS)-GOx microgels were approximately 130 nm. DLS measurements showed glucose-triggered microgel size changes upon glucose addition, which depended on buffer concentration. Enzymatically triggered drug release experiments using doxorubicin-loaded microgels with immobilized GOx demonstrated that drug release is strongly dependent on glucose and buffer concentration. The highest differences in release triggered by 5 and 25 mM glucose were observed in HEPES buffer at concentrations of 3 and 9 mM. Under these conditions, 80 and 52% of DOX were released with 25 mM glucose, while 47 and 28% of DOX were released with 5 mM glucose. The interstitial glucose concentration in a tumor ranges from ∼15 to 50 mM. Normal fasting blood glucose levels are about 5.5 mM, and postprandial (2 h after a meal) glucose levels should be less than 7.8 mM. The obtained results highlight the microgel's potential for drug delivery using the enhanced permeability and retention (EPR) effect, where drug release is controlled by enzymatically generated pH changes in response to elevated glucose concentrations.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of Piezoelectricity in Disease Diagnosis and Treatment: A Review.","authors":"Pratishtha Tripathi, Ashutosh Kumar Dubey","doi":"10.1021/acsbiomaterials.4c01346","DOIUrl":"10.1021/acsbiomaterials.4c01346","url":null,"abstract":"<p><p>Because of their unique electromechanical coupling response, piezoelectric smart biomaterials demonstrated distinctive capability toward effective, efficient, and quick diagnosis and treatment of a wide range of diseases. Such materials have potentiality to be utilized as wireless therapeutic methods with ultrasonic stimulation, which can be used as self-powered biomedical devices. An emerging advancement in the realm of personalized healthcare involves the utilization of piezoelectric biosensors for a range of therapeutic diagnosis such as diverse physiological signals in the human body, viruses, pathogens, and diseases like neurodegenerative ones, cancer, etc. The combination of piezoelectric nanoparticles with ultrasound has been established as a promising approach in sonodynamic therapy and piezocatalytic therapeutics and provides appealing alternatives for noninvasive treatments for cancer, chronic wounds, neurological diseases, etc. Innovations in implantable medical devices (IMDs), such as implantable piezoelectric energy generator (iPEG), offer significant advantages in improving physiological functioning and ability to power a cardiac pacemaker and restore the heart function. This comprehensive review critically evaluates the role of piezoelectricity in disease diagnosis and treatment, highlighting the implication of piezoelectric smart biomaterials for biomedical devices. It also discusses the potential of piezoelectric materials in healthcare monitoring, tissue engineering, and other medical applications while emphasizing future trends and challenges in the field.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xin Chu, Zhendi Fu, Yiting Liu, Yilong Dai, Jun Wang, Jueming Song, Zhibin Dong, Yang Yan, Kun Yu
{"title":"Mechanical Properties, Microstructure, Degradation Behavior, and Biocompatibility of Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg Guided Bone Regeneration Barrier Membranes Prepared Using a Powder Metallurgy Method.","authors":"Xin Chu, Zhendi Fu, Yiting Liu, Yilong Dai, Jun Wang, Jueming Song, Zhibin Dong, Yang Yan, Kun Yu","doi":"10.1021/acsbiomaterials.4c01068","DOIUrl":"10.1021/acsbiomaterials.4c01068","url":null,"abstract":"<p><p>Pure zinc exhibits low mechanical properties, making it unsuitable for use in guided bone regeneration (GBR) membranes. The present study focused on the preparation of Zn alloy GBR films using powder metallurgy, resulting in Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR films. The tensile strength of the pure Zn GBR film measured 85.9 MPa, while an elongation at break was 13.5%. In contrast, Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR films demonstrated significantly higher tensile strengths of 145.3 and 164.4 MPa, respectively, whereas elongations at break were 30.2% and 19.3%. The addition of Ti, Fe, and Mg substantially enhanced the mechanical properties of the zinc alloys. Corrosion analysis revealed that Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR membranes exhibited corrosion potentials of -1.298 and -1.316 V, respectively, with corresponding corrosion current densities of 12.11 and 13.32 μA/cm<sup>2</sup>. These values were translated to corrosion rates of 0.181 and 0.199 mm/year, indicating faster corrosion rates compared to pure Zn GBR membranes, which displayed a corrosion rate of 0.108 mm/year. Notably, both Zn-based alloy GBR membranes demonstrated excellent cytocompatibility, with a cytotoxicity rating of 0-1 in 25% leachate. Additionally, these membranes exhibited favorable osteogenic ability, as evidenced by the quantitative bone volume/tissue volume ratios (BV/TV) of new bone formation, which reached 30.3 ± 1.4% and 65.5 ± 1.8% for the Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR membranes, respectively, after 12 weeks of implantation. These results highlighted the significant potential for facilitating new bone growth. The proposed Zn-0.5Ti-0.5Fe and Zn-0.5Ti-0.5Mg alloy GBR membranes showed promise as viable biodegradable materials for future clinical studies.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhengyun Ling, Haoqian Zhang, Jian Zhao, Pengchao Wang, Ziyan An, Shuwei Xiao, Yanfeng Sun, Weijun Fu
{"title":"Electrostimulation-Based Decellularized Matrix Bladder Patch Promotes Bladder Repair in Rats.","authors":"Zhengyun Ling, Haoqian Zhang, Jian Zhao, Pengchao Wang, Ziyan An, Shuwei Xiao, Yanfeng Sun, Weijun Fu","doi":"10.1021/acsbiomaterials.4c00961","DOIUrl":"10.1021/acsbiomaterials.4c00961","url":null,"abstract":"<p><p>Bladder tissue engineering offers significant potential for repairing defects resulting from congenital and acquired conditions. However, the effectiveness of engineered grafts is often constrained by insufficient vascularization and neural regeneration. This study utilized four primary biomaterials─gelatin methacryloyl (GelMA), chitin nanocrystals (ChiNC), titanium carbide (MXene), and adipose-derived stem cells (ADSC)─to formulate two types of bioinks, GCM0.2 and GCM0.2-ADSC, in specified proportions. These bioinks were 3D printed onto bladder acellular matrix (BAM) patches to create BAM-GCM0.2 and BAM-GCM0.2-ADSC patches. The BAM-GCM0.2-ADSC patches underwent electrical stimulation to yield GCM0.2-ADSC-ES bladder patches. Employed for the repair of rat bladder defects, these patches were evaluated against a Control group, which underwent partial cystectomy followed by direct suturing. Our findings indicate that the inclusion of ADSC and electrical stimulation significantly enhances the regeneration of rat bladder smooth muscle (from [24.052 ± 2.782] % to [57.380 ± 4.017] %), blood vessels (from [5.326 ± 0.703] % to [12.723 ± 1.440] %), and nerves (from [0.227 ± 0.017] % to [1.369 ± 0.218] %). This research underscores the superior bladder repair capabilities of the GCM0.2-ADSC-ES patch and opens new pathways for bladder defect repair.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoqi Liu, Runliu Qian, Bo Li, Yingang Zhang, Yong Han
{"title":"Sono-Catalytic Tooth Whitening and Oral Health Enhancement with Oxygen Vacancies-Enriched Mesoporous TiO<sub>2</sub> Nanospheres: A Nondestructive Approach for Daily Tooth Care.","authors":"Xiaoqi Liu, Runliu Qian, Bo Li, Yingang Zhang, Yong Han","doi":"10.1021/acsbiomaterials.4c01185","DOIUrl":"10.1021/acsbiomaterials.4c01185","url":null,"abstract":"<p><p>Tooth discoloration and the breeding of oral microorganisms pose threats to both one's aesthetic appearance and oral health. Clinical whitening agents based on H<sub>2</sub>O<sub>2</sub> with high concentrations are effective in tooth whitening and bacterial elimination but may also cause enamel demineralization, gingival irritation, or cytotoxicity, necessitating professional supervision. Herein, leveraging sono-catalysis effects, a nondestructive and convenient tooth whitening strategy was developed, utilizing oxygen vacancies (OVs)-enriched mesoporous TiO<sub>2</sub> nanospheres. The introduction of OVs leads to TiO<sub>2</sub> bandgap narrowing, boosting the generation of reactive oxygen species (ROS) by TiO<sub>2</sub> under ultrasound treatment. Additionally, through the chemocatalysis effect, the ROS yield can be further augmented by employing OVs-enriched TiO<sub>2</sub> in conjunction with an extremely low concentration of H<sub>2</sub>O<sub>2</sub> (1%) during ultrasound treatment. Hence, under ultrasound treatment simulating daily tooth brushing using an electronic toothbrush, the combination of OVs-enriched TiO<sub>2</sub> and 1% H<sub>2</sub>O<sub>2</sub> proves to be effective in whitening teeth stained by tea, coffee, and mix juice. Furthermore, the combination of OVs-enriched TiO<sub>2</sub> and 1% H<sub>2</sub>O<sub>2</sub> demonstrates potent bacterial-killing and biofilm-eradicating effects under ultrasound treatment within an extremely short duration (5 min). Additionally, given the mesoporous structure, curcumin, serving as an anti-inflammatory agent, can be efficiently loaded into OVs-enriched TiO<sub>2</sub> and then controllably released through ultrasound treatment. The curcumin-loaded TiO<sub>2</sub> facilitates the transition of macrophages to the anti-inflammatory M2 phenotype, potentially alleviating oral inflammation induced by bacterial infection without showing any biotoxicity. The OVs-enriched TiO<sub>2</sub> based sono-catalysis tooth whitening procedure provides the convenience of whitening teeth during daily brushing without requiring professional supervision.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
João V Calazans Neto, Cícero A S Celles, Catia S A F de Andrade, Conrado R M Afonso, Bruna E Nagay, Valentim A R Barão
{"title":"Recent Advances and Prospects in β-type Titanium Alloys for Dental Implants Applications.","authors":"João V Calazans Neto, Cícero A S Celles, Catia S A F de Andrade, Conrado R M Afonso, Bruna E Nagay, Valentim A R Barão","doi":"10.1021/acsbiomaterials.4c00963","DOIUrl":"10.1021/acsbiomaterials.4c00963","url":null,"abstract":"<p><p>Titanium and its alloys, especially Ti-6Al-4V, are widely studied in implantology for their favorable characteristics. However, challenges remain, such as the high modulus of elasticity and concerns about cytotoxicity. To resolve these issues, research focuses on β-type titanium alloys that incorporate elements such as Mo, Nb, Sn, and Ta to improve corrosion resistance and obtain a lower modulus of elasticity compatible with bone. This review comprehensively examines current β titanium alloys, evaluating their mechanical properties, in particular the modulus of elasticity, and corrosion resistance. To this end, a systematic literature search was carried out, where 81 articles were found to evaluate these outcomes. In addition, this review also covers the formation of the alloy, processing methods such as arc melting, and its physical, mechanical, electrochemical, tribological, and biological characteristics. Because β-Ti alloys have a modulus of elasticity closer to that of human bone compared to other metal alloys, they help reduce stress shielding. This is important because the alloy allows for a more even distribution of forces by having a modulus of elasticity more similar to that of bone. In addition, these alloys show good corrosion resistance due to the formation of a noble titanium oxide layer, facilitated by the incorporation of β stabilizers. These alloys also show significant improvements in mechanical strength and hardness. Finally, they also have lower cytotoxicity and bacterial adhesion, depending on the β stabilizer used. However, there are persistent challenges that require detailed research in critical areas, such as optimizing the composition of the alloy to achieve optimal properties in different clinical applications. In addition, it is crucial to study the long-term effects of implants on the human body and to advance the development of cutting-edge manufacturing techniques to guarantee the quality and biocompatibility of implants.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An Antibiotic-Degrading Engineered Biofilm Platform to Combat Environmental Antibiotic Resistance.","authors":"Gökçe Özkul, Ebru Şahin Kehribar, Recep Erdem Ahan, Urartu Özgür Şafak Şeker","doi":"10.1021/acsbiomaterials.4c01074","DOIUrl":"10.1021/acsbiomaterials.4c01074","url":null,"abstract":"<p><p>The presence of antibiotics in natural water bodies is a growing problem regarding the occurrence of antibiotic resistance among various species. This is mainly caused by the excessive use of medical and veterinary antibiotics as well as the lack of effective treatment processes for eliminating residual antibiotics from wastewaters. In this study, we introduce a genetically engineered biomaterial as a solution for the effective degradation of one of the dominantly found antibiotics in natural water bodies. Our biomaterial harnesses laccase-type enzymes, which are known to attack specific types of antibiotics, i.e., fluoroquinolone-type synthetic antibiotics, and as a result degradation occurs. The engineered biomaterial is built using <i>Escherichia coli</i> biofilm protein CsgA as a scaffold, which is fused separately to two different laccase enzymes with the SpyTag-SpyCatcher peptide-protein duo. The designed biofilm materials were successful in degrading ciprofloxacin, as demonstrated with the data obtained from mass spectrometry analysis and cell viability assays.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanotechnology-Based Drug Delivery Systems for Treating Acute Kidney Injury.","authors":"Wanbing Qin, Jiaqi Huang, Manting Zhang, Mingwei Xu, Junbing He, Qinghua Liu","doi":"10.1021/acsbiomaterials.4c01385","DOIUrl":"10.1021/acsbiomaterials.4c01385","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a disease that is characterized by a rapid decline in renal function and has a relatively high incidence in hospitalized patients. Sepsis, renal hypoperfusion, and nephrotoxic drug exposure are the main causes of AKI. The major therapy measures currently include supportive treatment, symptomatic treatment, and kidney transplantation. These methods are supportive treatments, and their results are not satisfactory. Fortunately, many new treatments that markedly improve the AKI therapy efficiency are emerging. These include antioxidant therapy, ferroptosis therapy, anti-inflammatory therapy, autophagy therapy, and antiapoptotic therapy. In addition, the development of nanotechnology has further promoted therapeutic effects on AKI. In this review, we highlight recent advances in the development of nanocarriers for AKI drug delivery. Emphasis has been placed on the latest developments in nanocarrier modification and design. We also summarize the applications of different nanocarriers in AKI treatment. Finally, the advantages and challenges of nanocarrier applications in AKI are summarized, and several nanomedicines that have been approved for clinical trials to treat diverse kidney diseases are listed.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11480945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jamie L Hernandez, Shin-Tian Chien, My-Anh Doan, Ian T Suydam, Kim A Woodrow
{"title":"Antiretroviral (ARV) Properties Dictate Long-Acting Release and Tissue Partitioning Behaviors in Multidrug Subcutaneous Implants.","authors":"Jamie L Hernandez, Shin-Tian Chien, My-Anh Doan, Ian T Suydam, Kim A Woodrow","doi":"10.1021/acsbiomaterials.4c01290","DOIUrl":"10.1021/acsbiomaterials.4c01290","url":null,"abstract":"<p><p>Subcutaneous implants can provide patients with long-acting, compliance-independent drug dosing. For this reason, subcutaneous implants have shown emerging interest in human immunodeficiency virus (HIV) prevention. However, any successful long-acting HIV-prevention device will require multidrug dosing, which poses a challenge for formulation considering the physicochemically diverse selection of antiretroviral (ARV) candidates. As a method that has shown the capacity of efficient multidrug delivery, we assessed electrospun fiber implants composed of three synergistically potent ARVs and a biodegradable polymer selected by <i>in vitro</i> release studies. In mice, subcutaneous electrospun fiber implants exhibit burst release of the more hydrophilic drugs maraviroc (MVC) and raltegravir (RAL), which could be reduced <i>via</i> simple prewash treatments of the implants. Over an extended 120 day time frame, fiber implants show drug-specific differences in release time frames and magnitudes in blood serum. However, end-point drug tissue concentrations show that the most hydrophobic drug etravirine (ETR) remains in high concentrations within the implant and in local skin tissue biopsies. Furthermore, ETR is found to be capable of significant partitioning into lymph nodes, the lower female reproductive tract, and the rectum. Topologically smooth film implants also exhibit the same drug-dependent trends. Therefore, we illustrate that drug release and drug tissue partitioning are largely dictated by drug properties. Further, we find that the properties of ETR enable significant drug quantities within the tissues most relevant to HIV protection. Evidence from this work emphasizes the need for a greater focus on drug properties and prodrug strategies to enable relevant, extended, and targeted drug release.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}