Eric K. Long, Joseph F. Hassler, David M. Saylor, Ioan P. I. Gitsov, Logan Jolliffe, Augie Witkowski, Julie A. Alkatout, Greg Haugstad, Kimberly A. Chaffin
{"title":"End of Life Biocompatibility Assessment for Chronically Implanted Cardiac Leads","authors":"Eric K. Long, Joseph F. Hassler, David M. Saylor, Ioan P. I. Gitsov, Logan Jolliffe, Augie Witkowski, Julie A. Alkatout, Greg Haugstad, Kimberly A. Chaffin","doi":"10.1002/jbm.a.37932","DOIUrl":"https://doi.org/10.1002/jbm.a.37932","url":null,"abstract":"<p>Medical devices should be biocompatible throughout the entire lifecycle, but the evaluation for biocompatibility is typically performed on a new, fully finished device. While long-term implantable devices such as cardiac leads maintain function for more than a decade, studies have not addressed changes in extractable species throughout the implant life cycle. In this study, we performed extractables analysis on cardiac leads that were implanted in humans for times ranging from 3 to 130 months. The exhaustive extracts were analyzed using liquid chromatography coupled to mass spectrometry to identify and relatively quantify extractable species. Over implant times exceeding a decade, no new species were formed, and the quantity of each class of mobile species remained constant or decreased over time. Polyurethane oligomers, a byproduct of the polymerization route, generally remained at constant levels, suggesting that there is little to no driving force for them to enter the surrounding tissue. Small molecule additives, such as the antioxidant Irganox 1076, contained within the polyurethane outer coating, decreased at a rate that was consistent with diffusional release rather than reactive consumption. These results support two important conclusions. First, the chemical profile of the mobile species does not change over the implanted lifecycle, indicating the biocompatibility of durable cardiac leads does not change over time. Second, the toxicological assumption that all mobile species identified in exhaustive extractions of a new device are released upon implant is extremely conservative when contrasted with the diffusional release rates measured in the human explanted leads studied herein.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37932","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118239","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}
Zhaojun Wu, Wenqing Hou, Jiachen Lu, Haoyu Zhao, Song Chen, Tailin Guo, Tingting Li
{"title":"Piezo1 Is an Early Mediator During Topography-Stimulated Osteogenic Differentiation of Bone Mesenchymal Stem Cells","authors":"Zhaojun Wu, Wenqing Hou, Jiachen Lu, Haoyu Zhao, Song Chen, Tailin Guo, Tingting Li","doi":"10.1002/jbm.a.37931","DOIUrl":"https://doi.org/10.1002/jbm.a.37931","url":null,"abstract":"<div>\u0000 \u0000 <p>Micro/nano-topographies (MNTs) of biomaterials are well-known to influence osteoblast differentiation, although the underlying mechanisms remain incompletely understood. Piezo1 is involved in mechanotransduction in various cell types, and we hypothesized that Piezo1 may play a key role in osteogenic differentiation through the NFATc1-Wnt/β-catenin or YAP signaling pathways. To test this hypothesis, polished titanium plates (PT) and titanium plates with TiO<sub>2</sub> nanotubes (TNT-30 and TNT-100) were used. Experimental results showed that TNT-100 increased the gene expression and activation of Piezo1, upregulating osteogenic genes such as NFATc1, Wnt3a, and β-catenin, and promoting the nuclear localization of NFATc1, β-catenin, and YAP compared to PT. The influx of Ca<sup>2+</sup> through Piezo1, activated by MNTs, initiated the signaling cascades. Furthermore, compared to TRPV4, another recently reported mediator in MNTs-stimulated osteogenic differentiation, Piezo1 responded to MNTs much faster. These findings suggest that Piezo1 acts as an early mediator of osteogenic differentiation stimulated by MNTs in BMSCs.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144117869","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}
Rodolphe Migneret, Guillaume Leks, Julie Favre, Emeline Lobry, Hamdi Jmal, Guy Schlatter, Isabelle Talon, Nadia Bahlouli, Anne Hébraud
{"title":"Bilayer Electrospun Polyurethane Membrane With Tunable Elastomeric Properties for the Treatment of Congenital Diaphragmatic Hernia","authors":"Rodolphe Migneret, Guillaume Leks, Julie Favre, Emeline Lobry, Hamdi Jmal, Guy Schlatter, Isabelle Talon, Nadia Bahlouli, Anne Hébraud","doi":"10.1002/jbm.a.37926","DOIUrl":"https://doi.org/10.1002/jbm.a.37926","url":null,"abstract":"<p>Congenital diaphragmatic hernia is a rare condition characterized by the development of a defect in the diaphragm during early embryogenesis. For the most severe cases, when the diaphragmatic defect is large, the gap is currently closed by a prosthetic patch made of e-PTFE (Gore-Tex) materials, which lack sufficient elasticity, causing early rupture of stitches and subsequent hernia recurrence. In this study, we introduce a novel thermoplastic polyurethane membrane designed to accommodate the child's growth. This film/fiber bilayer membrane, produced in a single continuous electrospinning process by varying the flow rate, exhibits a smooth surface to prevent adhesion of the tissues on the abdominal side and a rough surface to promote adhesion of the diaphragm muscle on the thoracic side. Mechanical properties of the membrane were evaluated under various deformation modes, including uniaxial tensile tests and equibiaxial tensile tests by the bubble inflation technique. We demonstrated the ability to tune the elastic modulus by adjusting the thickness of the film and fibers, achieving greater stretchability than specified for supporting child growth and respiration both in uniaxial and inflation tests. Moreover, in vitro biological tests showed that the membrane promotes cellular colonization without pro-inflammatory effect, making it a promising candidate to replace the currently used prosthesis.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37926","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143938811","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}
Sabrina C. Mierswa, Erika E. Wheeler, Ayla N. Apsey, Oju Jeon, Eben Alsberg, J. Kent Leach
{"title":"Mesenchymal Stromal Cell Chondrogenic Differentiation Induced by Continuous Stiffness Gradient in Photocrosslinkable Hydrogels","authors":"Sabrina C. Mierswa, Erika E. Wheeler, Ayla N. Apsey, Oju Jeon, Eben Alsberg, J. Kent Leach","doi":"10.1002/jbm.a.37928","DOIUrl":"https://doi.org/10.1002/jbm.a.37928","url":null,"abstract":"<div>\u0000 \u0000 <p>Chondrogenic differentiation of stem and progenitor cells is dependent on the biophysical properties of the surrounding matrix. Current biomaterials-based approaches for chondrogenesis are limited to discrete platforms, slowing our ability to interrogate the role of mechanical cues such as substrate stiffness and other signals. Thus, novel platforms must incorporate a range of biophysical properties within a single construct to effectively assess changes in cell response. We encapsulated human mesenchymal stromal cells (MSCs) within biodegradable, photocurable oxidized, and methacrylated alginate (OMA). Cell-laden hydrogels were crosslinked when exposed to light through a grayscale photomask to form substrates with a continuous stiffness gradient. We also tested the influence of the adhesive ligand Arg-Gly-Asp (RGD) on chondrogenic differentiation. Compared to unmodified gels possessing uniform biophysical properties, RGD-modified OMA hydrogels with the same modulus promoted chondrogenic differentiation of MSCs as evidenced by gene expression, matrix deposition, and histological analysis. MSCs entrapped in OMA hydrogels exhibiting a biologically relevant stiffness gradient (2–13 kPa over 8 mm) demonstrated increased chondrogenic differentiation with increases in stiffness. MSC chondrogenic differentiation was dependent upon the ability to mechanosense the modulus of the surrounding matrix, confirmed by the addition of Latrunculin A (LatA), a soluble inhibitor of actin polymerization. These findings validate a methodology for customizing hydrogel platforms for chondrogenic differentiation and identifying the interplay of key variables to instruct cell function.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939017","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}
Linsen Li, Di An, Jinhu Zhao, Yue Yu, Yating Zeng, Xiayan Yang, Qifeng Yu, Ke Kang, Yao Wu, Qiangying Yi
{"title":"Versatile Coating via Programmed Assembly of miR-155 Inhibitor and Endothelial Affinity Peptide","authors":"Linsen Li, Di An, Jinhu Zhao, Yue Yu, Yating Zeng, Xiayan Yang, Qifeng Yu, Ke Kang, Yao Wu, Qiangying Yi","doi":"10.1002/jbm.a.37923","DOIUrl":"https://doi.org/10.1002/jbm.a.37923","url":null,"abstract":"<div>\u0000 \u0000 <p>Medical implants serve as pivotal therapeutic interventions for cardiovascular diseases. Nevertheless, challenges including endothelial injury, excessive smooth muscle cell migration, and inflammatory responses associated with implantation hinder their long-term adoption in vivo. In this work, a versatile coating of cardiovascular implants was constructed by the remarkable adhesive properties of dopamine and the precision and efficiency of click chemistry. The functional coating was obtained through programmed assembly of heparin, miR-155 inhibitor, and endothelial cell affinity peptide. Cellular experiments have demonstrated that this coating could modulate macrophage phenotype through anti-miR155 inhibitors, thereby inhibiting the release of inflammatory factors and improving the inflammatory environment on the surface. Furthermore, this coating could also promote the adhesion and proliferation of endothelial cells while inhibiting the excessive proliferation of smooth muscle cells, thereby ensuring the endothelialization of the implant surface. Additionally, animal experiments have revealed the coating's exceptional anticoagulant properties, significantly reducing the formation of thrombus. With its simple and efficient preparation process and excellent performance, this coating emerges as a promising candidate for promoting early endothelialization and improving the performance of cardiovascular implants.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939113","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}
Takanori Fukunaga, Joseph J. Pearson, Ryan Cree Miller, Changli Zhang, Mohammed Lakrat, Lisbet Haglund, Martha Elena Diaz-Hernandez, Johnna S. Temenoff, Hicham Drissi
{"title":"PDGF-Releasing Hydrogels for Enhanced Proliferation of Human Nucleus Pulposus Cells","authors":"Takanori Fukunaga, Joseph J. Pearson, Ryan Cree Miller, Changli Zhang, Mohammed Lakrat, Lisbet Haglund, Martha Elena Diaz-Hernandez, Johnna S. Temenoff, Hicham Drissi","doi":"10.1002/jbm.a.37918","DOIUrl":"https://doi.org/10.1002/jbm.a.37918","url":null,"abstract":"<div>\u0000 \u0000 <p>Hydrogels offer a promising solution for sustained and controlled drug delivery and cell-tissue biocompatibility. In the intervertebral disc (IVD), delivering growth factors faces challenges due to the antagonistic inflammatory environment and continuous mechanical stress, which can degrade biological agents and may reduce their local activity. To address this, we investigated the prolonged release of platelet-derived growth factor isoforms BB (PDGF-BB) and AB (PDGF-AB) by using N-desulfated heparin methacrylamide (Hep<sup>-N</sup>) crosslinked within matrix-metalloproteinase sensitive poly(ethylene glycol) (PEG) hydrogels. Using electrostatic interactions between the heparin derivative and PDGF, we optimized a sustained release dose of PDGF-BB from the hydrogel in the presence of collagenase to mimic the in vivo environment. We then assessed the effects of PDGF released from PEG-hydrogel on human nucleus pulposus (NP) Cells. The MTT assay confirmed that 100 and 200 ng doses significantly increased cell viability by 2.52-fold and 2.46-fold on Day 3, respectively. RT-qPCR analysis revealed that PDGF-AB and PDGF-BB upregulated the expression of proliferation marker Ki-67 (MKI67) on both Day 3 and Day 5. Additionally, collagen type II alpha 1 chain (COL2A1) was significantly upregulated in the PDGF-AB group on Day 5, indicating potential anabolic effects. These findings could pave the way for long-term in vivo studies on sustainable PDGF treatment for IVD degeneration.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925950","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":"Preparation, Physicochemical Characterization, and In Vitro and In Vivo Osteogenic Evaluation of Reinforced PLLA-PLCL/HA Resorbable Membranes","authors":"Zheng Fu, Jing Wang, Yuhan Wu, Wenyi Zeng, Chenguang Zhang, Yang Sun, Xiaoshan Fan, Yucheng Huang, Feilong Deng, Jiayun Xu","doi":"10.1002/jbm.a.37925","DOIUrl":"https://doi.org/10.1002/jbm.a.37925","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to develop reinforced poly(L-lactide)-poly(L-lactide-co-ε-caprolactone)/hydroxyapatite (PLLA-PLCL/HA) resorbable membranes for guided bone regeneration (GBR), focusing on optimizing the degradation rate by adjusting PLLA molecular weight. We aimed to achieve a balance between mechanical strength and bioactivity to enhance the efficacy of bone regeneration. PLLA-PLCL/HA membranes with varying degradation rates were fabricated by modifying the molecular weight of PLLA. The membranes were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), andx-ray diffraction (XRD). Mechanical properties were evaluated using three-point bending tests, and in vitro cytocompatibility was assessed through MC3T3-E1 cell adhesion and proliferation. For in vivo experiments, a cranial defect mouse model was used to investigate degradation and osteogenic potential, and bone regeneration was evaluated using micro-CT, histological staining, and immunohistochemistry. The reinforced membranes exhibited superior bending strength compared to collagen membranes. The in vitro studies confirmed excellent cytocompatibility, and in vivo results showed that membranes with slower early stage degradation promoted bone regeneration, emphasizing the importance of degradation control in GBR membranes. The optimized PLLA-PLCL/HA membranes, which combine enhanced mechanical properties and controlled biodegradability, are promising candidates for clinical GBR applications.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919533","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}
Qingling Xu, Xinhui Chen, Shuwei Sun, Chunyige Zhao, Linxin Shi, Han Cheng, Ying Liu, Chunying Shi, Xiang Ao
{"title":"Vascular Endothelial Growth Factor-Mimetic Peptide and Mitochondria-Targeted Antioxidant-Loaded Hydrogel System Improves Repair of Myocardial Infarction in Mice","authors":"Qingling Xu, Xinhui Chen, Shuwei Sun, Chunyige Zhao, Linxin Shi, Han Cheng, Ying Liu, Chunying Shi, Xiang Ao","doi":"10.1002/jbm.a.37924","DOIUrl":"https://doi.org/10.1002/jbm.a.37924","url":null,"abstract":"<div>\u0000 \u0000 <p>Myocardial infarction (MI) is a pathological state characterized by persistent ischemia of the heart. Following MI, the structural and functional remodeling of the myocardium and vasculature involves oxidative stress and mitochondrial dysfunction, which exacerbate myocardial injury. Currently, there are limited effective treatments available to alleviate MI-induced damage. Vascular endothelial growth factor-mimetic (QK) peptides and mitochondria-targeted Szeto–Schiller (SS31) peptides have been extensively investigated for their therapeutic potential in various ischemic cardiomyopathies. However, traditional topical agents used in myocardial ischemia treatment suffer from limitations such as transient retention or undesirable diffusion of the drug. Consequently, a controlled drug delivery system capable of delivering QK and SS31 has gained significant attention for repair. In this study, we constructed self-assembled nanofibrous hydrogels incorporating QK and SS31 with customizable peptide amphiphilic (PA) molecules, resulting in PA1-QK and PA2-SS31 formulations. In vitro experiments demonstrated that both QK and SS31 effectively inhibited mitochondrial damage and apoptosis in a cellular hypoxia/reoxygenation (H/R) model. In vivo studies using a mouse MI model revealed that PA1-QK and PA2-SS31 significantly promoted vascular regeneration, attenuated mitochondrial dysfunction and apoptosis, and facilitated the recovery of cardiac structure and function. These results suggest that PA1-QK and PA2-SS31-loaded self-assembled nanofiber hydrogels represent an effective drug delivery system for promoting regenerative repair of myocardium and blood vessels following MI.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919525","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}
Clyde Overby, Brittany Abraham, Emmanuella Adjei-Sowah, Alyson March, Kevin Ling, Sayantani Basu, Danielle S. W. Benoit
{"title":"A Rapid Manual Solid Phase Peptide Synthesis Method for High-Throughput Peptide Production","authors":"Clyde Overby, Brittany Abraham, Emmanuella Adjei-Sowah, Alyson March, Kevin Ling, Sayantani Basu, Danielle S. W. Benoit","doi":"10.1002/jbm.a.37922","DOIUrl":"https://doi.org/10.1002/jbm.a.37922","url":null,"abstract":"<p>Solid phase peptide synthesis (SPPS) techniques are critical for developing and using peptides in various biomedical applications. However, typical synthesis routes used in SPPS are either resource-intensive (e.g., with automated synthesis or commercial services) or time-consuming (e.g., with manual benchtop synthesis). Here, a rapid manual synthesis method was developed to produce up to 8 peptides with fast cycle times simultaneously. Peptides synthesized manually were of equivalent or superior quality to those produced by in-house microwave-assisted automated peptide synthesis, with higher average crude purity of 70% compared to 50%. The method significantly reduced synthesis time, enabling the parallel coupling of up to 8 amino acids simultaneously in 15–20 min, as opposed to traditional benchtop peptide synthesis, which requires 80–150 min per amino acid. This approach offers an intermediate throughput between milligram-scale libraries and gram-scale single peptide synthesis, enabling rapid iteration for novel peptide designs without the need for expensive automated systems. As a result, peptide modifications, including incorporation of unnatural amino acids, can be explored, accelerating the development of peptides for a wide range of applications.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37922","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897103","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}
T. Buchholz, C. Siverino, T. F. Moriarty, E. J. Sheehy, F. J. O'Brien, D. Nehrbass, S. Arveladze, C. Constant, S. Hassouna Elsayed, M. Yan, H. A. Awad, S. Zeiter, M. J. Allen
{"title":"Antibiotic-Loaded Polymer-Calcium Phosphate Scaffold for Treating Orthopedic Device-Related Infection in a Rabbit Segmental Bone Defect Model","authors":"T. Buchholz, C. Siverino, T. F. Moriarty, E. J. Sheehy, F. J. O'Brien, D. Nehrbass, S. Arveladze, C. Constant, S. Hassouna Elsayed, M. Yan, H. A. Awad, S. Zeiter, M. J. Allen","doi":"10.1002/jbm.a.37917","DOIUrl":"https://doi.org/10.1002/jbm.a.37917","url":null,"abstract":"<div>\u0000 \u0000 <p>Treatment of orthopedic device-related infection (ORDI) generally requires a combination of medical and surgical interventions for successful treatment outcomes. Many cases are treated with a two-stage revision, whereby contaminated implants and necrotic tissues are removed, and dead space is managed with a temporary, non-resorbable polymethyl methacrylate (PMMA) spacer loaded with antibiotics. Weeks later, this is replaced with a bone graft or similar material to aid bone healing. However, this two-stage approach is quite a burden for the patient, and infection may still recur. The use of a 3D-printed, absorbable, antibiotic-releasing material that also promotes bone healing would be a promising alternative that produces the exact geometry of the missing bone and eliminates the need for a second surgery. In this study, we investigated whether a novel 3D-printed, antibiotic-loaded, osteoconductive calcium phosphate scaffold (CPS) is effective in the single-stage revision of an infected segmental bone defect model in rabbits. A 5-mm segmental defect of the radius of female New Zealand White rabbits (<i>n</i> = 64), stabilized with cerclage wire, was inoculated with <i>Staphylococcus aureus</i>. After 4 weeks, the infected bone fragment was removed, the site debrided, and the bone defect was either left empty (Control group) or filled with a PMMA spacer with gentamicin, CPS loaded with rifampicin or non-loaded CPS. The animals were also managed with systemic cefazolin for 4 weeks. An additional group received vancomycin-loaded CPS without adjunctive systemic antibiotic therapy. All animals were euthanized 8 weeks after revision and assessed by quantitative bacteriology or semiquantitative histopathology. The antibiotic-loaded scaffolds (PMMA-Genta and CPS-Rif) in the animals receiving systemic antibiotic treatment resulted in a reduction in bacterial count at euthanasia compared to controls (rabbits receiving systemic antibiotic alone and in which the defect was left empty). The PMMA-Genta induced a significant CFU reduction (<i>p</i> = 0.0486) compared to controls. The infection rate was also reduced from 80% in the control group to 50% for the groups receiving local and systemic antibiotics. The CPS-Vanco group for local delivery without adjunctive systemic antibiotic therapy resulted in a lower infection rate, but the CFUs in these samples at euthanasia were comparable with those of the control group. The findings show that treating an ODRI with PMMA-Genta yields the best results for infection eradication; however, it does not provide the reconstruction opportunity that the antibiotic-loaded CPS does. Even though it is not comparable to the PMMA-Genta, the antibiotic-loaded CPS showed a reduction in infection rates. The use of local antibiotics alone is insufficient to eradicate the infection.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143883820","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}