The degree of bone ingrowth in the porous implant is influenced by design parameters (pore size, thickness of porous buttresses, and core material). The purpose of this numerical study was to assess how the variation of the implant's design parameters influences bone ingrowth into a porous hip stem, as proposed by the authors in a previous study. Eight macromodels of the implant-bone structure were developed based on the design of experiment approach (full factorial design with three parameters and two levels each). These finite element (FE) macromodels were solved in ANSYS under normal walking and stair climbing loadings and physiological boundary conditions. A 3D submodel corresponding to each macromodel was considered for bone ingrowth simulation. Total displacement at the cut boundaries of the macromodels was mapped to submodels. Bone ingrowth was predicted by integrating a phenomenological mechanoregulatory algorithm with FE analysis of the submodels. The ANOVA and regression analysis were performed between design parameters and responses (bone ingrowth and elastic modulus of newly formed tissues). Within the first month following surgery, the study predicted a significant amount of bone ingrowth (32%–72%) even in proximal regions and a smaller amount of fibrous tissue ingrowth (0.5%–3.5%) in all submodels. At equilibrium iteration, the average Young's modulus of the newly formed bone tissue layer ranged from 380 to 1200 MPa, considering all the submodels. The higher pore size, FGM core and half-porous buttresses provide better bone ingrowth that results in a higher elastic modulus of the newly developed tissue inside the pores of the hip stem. This bone ingrowth is expected to potentially improve long-term fixation and stability of the hip stem, reducing the risk of implant loosening.
{"title":"Effect of Design Parameters of an Uncemented Hip Stem on Bone Ingrowth—Finite Element Analyses Integrated With Mechanoregulatory Algorithm and Design of Experiment","authors":"Tanmoy Loha, Bidyut Pal","doi":"10.1002/jbm.b.35691","DOIUrl":"10.1002/jbm.b.35691","url":null,"abstract":"<div>\u0000 \u0000 <p>The degree of bone ingrowth in the porous implant is influenced by design parameters (pore size, thickness of porous buttresses, and core material). The purpose of this numerical study was to assess how the variation of the implant's design parameters influences bone ingrowth into a porous hip stem, as proposed by the authors in a previous study. Eight macromodels of the implant-bone structure were developed based on the design of experiment approach (full factorial design with three parameters and two levels each). These finite element (FE) macromodels were solved in ANSYS under normal walking and stair climbing loadings and physiological boundary conditions. A 3D submodel corresponding to each macromodel was considered for bone ingrowth simulation. Total displacement at the cut boundaries of the macromodels was mapped to submodels. Bone ingrowth was predicted by integrating a phenomenological mechanoregulatory algorithm with FE analysis of the submodels. The ANOVA and regression analysis were performed between design parameters and responses (bone ingrowth and elastic modulus of newly formed tissues). Within the first month following surgery, the study predicted a significant amount of bone ingrowth (32%–72%) even in proximal regions and a smaller amount of fibrous tissue ingrowth (0.5%–3.5%) in all submodels. At equilibrium iteration, the average Young's modulus of the newly formed bone tissue layer ranged from 380 to 1200 MPa, considering all the submodels. The higher pore size, FGM core and half-porous buttresses provide better bone ingrowth that results in a higher elastic modulus of the newly developed tissue inside the pores of the hip stem. This bone ingrowth is expected to potentially improve long-term fixation and stability of the hip stem, reducing the risk of implant loosening.</p>\u0000 </div>","PeriodicalId":15269,"journal":{"name":"Journal of biomedical materials research. Part B, Applied biomaterials","volume":"113 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Achmad Syaifudin, Zafarel Zeta Averil, Maulana Y. Izzuddin, Amaliya Rasyida, Siti Nurkhamiddah, Lukman Hakim, Katsuhiko Sasaki
Ureteral stents are flexible implants commonly made from polyurethane and silicone. Some ureteral stents used in Indonesia experience damage upon removal, even when patients arrive on time for stent removal. This study was conducted to investigate the effect of the mechanical properties of ureteral stent materials on their service life. The tests conducted included tensile testing and material composition analysis using two different Fourier Transform Infrared Spectroscopy (FTIR) devices. In addition, to determine the presence of material mixtures, composition testing was also performed using SEM/EDX. Five samples of ureteral stent products commonly available in Indonesia were selected for this study: two samples with a service life of 2 months, one sample with a 6-month service life, and two samples with a 12-month service life. Analysis of Variance (ANOVA) testing was carried out to confirm correlations between the investigated variables. The results showed that there was no significant effect of the material's mechanical properties, either tensile strength or elastic modulus, on the service life of the ureteral stent. The results showed no statistically significant correlation (p > 0.05) between tensile strength or elastic modulus and service life. Instead, material choice should match intended duration: polyurethane for short-term (< 6 months) and silicone for long-term (> 6 months). Recommended minimum tensile strength is 11.81 MPa for silicone and 9.11 MPa for polyurethane. These results provide practical guidance for designing ureteral stents based on service life rather than mechanical properties.
{"title":"How Mechanical Properties of Ureteral Stent Material Affect Its Service Life","authors":"Achmad Syaifudin, Zafarel Zeta Averil, Maulana Y. Izzuddin, Amaliya Rasyida, Siti Nurkhamiddah, Lukman Hakim, Katsuhiko Sasaki","doi":"10.1002/jbm.b.35692","DOIUrl":"10.1002/jbm.b.35692","url":null,"abstract":"<div>\u0000 \u0000 <p>Ureteral stents are flexible implants commonly made from polyurethane and silicone. Some ureteral stents used in Indonesia experience damage upon removal, even when patients arrive on time for stent removal. This study was conducted to investigate the effect of the mechanical properties of ureteral stent materials on their service life. The tests conducted included tensile testing and material composition analysis using two different Fourier Transform Infrared Spectroscopy (FTIR) devices. In addition, to determine the presence of material mixtures, composition testing was also performed using SEM/EDX. Five samples of ureteral stent products commonly available in Indonesia were selected for this study: two samples with a service life of 2 months, one sample with a 6-month service life, and two samples with a 12-month service life. Analysis of Variance (ANOVA) testing was carried out to confirm correlations between the investigated variables. The results showed that there was no significant effect of the material's mechanical properties, either tensile strength or elastic modulus, on the service life of the ureteral stent. The results showed no statistically significant correlation (<i>p</i> > 0.05) between tensile strength or elastic modulus and service life. Instead, material choice should match intended duration: polyurethane for short-term (< 6 months) and silicone for long-term (> 6 months). Recommended minimum tensile strength is 11.81 MPa for silicone and 9.11 MPa for polyurethane. These results provide practical guidance for designing ureteral stents based on service life rather than mechanical properties.</p>\u0000 </div>","PeriodicalId":15269,"journal":{"name":"Journal of biomedical materials research. Part B, Applied biomaterials","volume":"113 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nikolaos P. Tzavellas, Natalia Atzemoglou, Efstathios L. Pavlidis, Alkinoos Nikolis, Georgios S. Markopoulos, Konstantinos I. Tsamis, Dimitrios Peschos, Yannis V. Simos, Lampros Lakkas
Valvular heart disease (VHD) represents a significant global health challenge, affecting over 2.5% of the population and disproportionately impacting older adults due to age-related degenerative processes. Current treatment options—mechanical and bioprosthetic valves—both present substantial limitations that impact patient quality of life and long-term outcomes. Mechanical valves require lifelong anticoagulation with associated bleeding risks, while bioprosthetic valves suffer from limited durability, typically requiring replacement within 10–15 years. These limitations are particularly problematic for pediatric and young adult populations, who face multiple surgical interventions throughout their lifetime. Decellularized scaffolds have emerged as promising alternatives due to their natural extracellular matrix architecture and potential for recipient cell repopulation and growth, making them especially valuable for pediatric patients. However, these scaffolds face several critical biological challenges that have prevented widespread clinical adoption, including suboptimal recellularization patterns, inflammatory responses, calcification propensity, and structural degradation over time. Recent advances in gene editing technologies, particularly CRISPR-Cas9 and emerging base editing techniques, offer unprecedented opportunities to overcome these limitations by enabling precise molecular-level tissue modifications. These technologies could enhance scaffold biocompatibility, promote favorable cellular responses, prevent calcification, and improve structural integrity. This review explores how combining decellularized scaffold approaches with gene editing techniques could transform heart valve treatment. We examine the potential of this integrated approach to create valve replacements with improved durability and biocompatibility and propose pathways for translating these innovations into clinical practice. The convergence of these technologies holds particular promise for younger patients who would benefit most from heart valves capable of growth and long-term function without repeated surgical interventions.
{"title":"Revolutionizing Heart Valve Therapy: A Translational Framework for Combining Decellularized Scaffolds With Genetic Modification","authors":"Nikolaos P. Tzavellas, Natalia Atzemoglou, Efstathios L. Pavlidis, Alkinoos Nikolis, Georgios S. Markopoulos, Konstantinos I. Tsamis, Dimitrios Peschos, Yannis V. Simos, Lampros Lakkas","doi":"10.1002/jbm.b.35686","DOIUrl":"10.1002/jbm.b.35686","url":null,"abstract":"<p>Valvular heart disease (VHD) represents a significant global health challenge, affecting over 2.5% of the population and disproportionately impacting older adults due to age-related degenerative processes. Current treatment options—mechanical and bioprosthetic valves—both present substantial limitations that impact patient quality of life and long-term outcomes. Mechanical valves require lifelong anticoagulation with associated bleeding risks, while bioprosthetic valves suffer from limited durability, typically requiring replacement within 10–15 years. These limitations are particularly problematic for pediatric and young adult populations, who face multiple surgical interventions throughout their lifetime. Decellularized scaffolds have emerged as promising alternatives due to their natural extracellular matrix architecture and potential for recipient cell repopulation and growth, making them especially valuable for pediatric patients. However, these scaffolds face several critical biological challenges that have prevented widespread clinical adoption, including suboptimal recellularization patterns, inflammatory responses, calcification propensity, and structural degradation over time. Recent advances in gene editing technologies, particularly CRISPR-Cas9 and emerging base editing techniques, offer unprecedented opportunities to overcome these limitations by enabling precise molecular-level tissue modifications. These technologies could enhance scaffold biocompatibility, promote favorable cellular responses, prevent calcification, and improve structural integrity. This review explores how combining decellularized scaffold approaches with gene editing techniques could transform heart valve treatment. We examine the potential of this integrated approach to create valve replacements with improved durability and biocompatibility and propose pathways for translating these innovations into clinical practice. The convergence of these technologies holds particular promise for younger patients who would benefit most from heart valves capable of growth and long-term function without repeated surgical interventions.</p>","PeriodicalId":15269,"journal":{"name":"Journal of biomedical materials research. Part B, Applied biomaterials","volume":"113 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.b.35686","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145488734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Significant anti-inflammatory qualities are exhibited by nanoparticles, which are essential for efficient burn wound healing. Numerous methods based on nanoparticles have proven successful in reducing excessive inflammation, avoiding infection, and encouraging tissue regeneration. In this study, we describe the creation of zinc nanoparticles for the treatment of burn wounds using an aqueous extract from Pulsatilla chinensis leaves. Several analytical techniques, including XRD, UV–Vis, FE-SEM, and FT-IR, were used to characterize the final biomaterial. ZnNPs@Pulsatilla chinensis was used to treat 75 Wistar rats' induced burn injuries. For 30 days, the animals received basal, tetracycline 3%, ZnNPs@Pulsatilla chinensis 1%, and Pulsatilla chinensis leaf aqueous extract 1% therapy. The reduction in burn wound area as well as molecular and histological features were used to assess the effectiveness of the treatment. One group served as the control group. All groups treated with ZnNPs@Pulsatilla chinensis had mean wound surfaces that were greater than those of the control group. VEGF, PDGF, bFGF, and EGF were all elevated by ZnNPs@Pulsatilla chinensis ointment. When combined, these findings provide credence to the therapeutic application of ZnNPs@Pulsatilla chinensis as a strong ointment that might be suggested for the healing of burn wounds.
{"title":"Formulation of a Novel Ointment by the Pulsatilla chinensis Leaf Aqueous–Based Zinc Nanoparticles for Healing the Burn Wound in Rat","authors":"Jingli Jia, Jingjing Zhang, Yi Li","doi":"10.1002/jbm.b.35689","DOIUrl":"10.1002/jbm.b.35689","url":null,"abstract":"<div>\u0000 \u0000 <p>Significant anti-inflammatory qualities are exhibited by nanoparticles, which are essential for efficient burn wound healing. Numerous methods based on nanoparticles have proven successful in reducing excessive inflammation, avoiding infection, and encouraging tissue regeneration. In this study, we describe the creation of zinc nanoparticles for the treatment of burn wounds using an aqueous extract from <i>Pulsatilla chinensis</i> leaves. Several analytical techniques, including XRD, UV–Vis, FE-SEM, and FT-IR, were used to characterize the final biomaterial. ZnNPs@<i>Pulsatilla chinensis</i> was used to treat 75 Wistar rats' induced burn injuries. For 30 days, the animals received basal, tetracycline 3%, ZnNPs@<i>Pulsatilla chinensis</i> 1%, and <i>Pulsatilla chinensis</i> leaf aqueous extract 1% therapy. The reduction in burn wound area as well as molecular and histological features were used to assess the effectiveness of the treatment. One group served as the control group. All groups treated with ZnNPs@<i>Pulsatilla chinensis</i> had mean wound surfaces that were greater than those of the control group. VEGF, PDGF, bFGF, and EGF were all elevated by ZnNPs@<i>Pulsatilla chinensis</i> ointment. When combined, these findings provide credence to the therapeutic application of ZnNPs@<i>Pulsatilla chinensis</i> as a strong ointment that might be suggested for the healing of burn wounds.</p>\u0000 </div>","PeriodicalId":15269,"journal":{"name":"Journal of biomedical materials research. Part B, Applied biomaterials","volume":"113 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145482188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Madalena S. Oliveira, Francisco de Assis Dórea Neto, Alessandra Estrela-Lima, Paula Laise Ribeiro de Oliveira, Débora Passos Hinojosa Schaffer, Luis Alberto Loureiro dos Santos, Eduardo Jose Nassar, Arianne Pontes Oriá
This study introduces a comparative in vivo evaluation of four synthetic biomaterials with distinct resorption profiles—double-setting alpha-tricalcium phosphate (α-TCPdp), α-TCPdp combined with a lactic-co-glycolic acid and poly(isoprene) copolymer (PLGA/PI), and two 3D-printed polymers, acrylonitrile butadiene styrene (ABS) and polyamide (PA)—for reconstruction of critical-sized mandibular defects in rabbits. Twenty animals were divided into four groups (n = 10 defects each) and evaluated at 30, 60, and 120 days post-implantation through clinical, radiographic, histopathological, and scanning electron microscopy analyses. All implants exhibited excellent biocompatibility, osseointegration, and absence of adverse tissue reactions. ABS and PA promoted significantly greater early bone neoformation compared to α-TCP-based cements, whereas α-TCPdp and α-TCPdp + PLGA/PI underwent gradual bone replacement via surface degradation and creeping substitution. The addition of PLGA/PI reduced the inflammatory response without compromising osteoconductivity. SEM analysis, enhanced by an adapted decalcification protocol, confirmed continuous bone ingrowth and intimate bone–implant contact. This work provides the first direct comparison of α-TCPdp and polymer-based implants in a mandibular critical defect model, highlighting the potential of both absorbable and non-absorbable biomaterials for customized craniofacial reconstruction.
{"title":"In Vivo Evaluation of Porous Implants: Alpha-Tricalcium Phosphate Cement and Polymers Obtained by Different Manufacturing Processes","authors":"Maria Madalena S. Oliveira, Francisco de Assis Dórea Neto, Alessandra Estrela-Lima, Paula Laise Ribeiro de Oliveira, Débora Passos Hinojosa Schaffer, Luis Alberto Loureiro dos Santos, Eduardo Jose Nassar, Arianne Pontes Oriá","doi":"10.1002/jbm.b.35688","DOIUrl":"10.1002/jbm.b.35688","url":null,"abstract":"<div>\u0000 \u0000 <p>This study introduces a comparative in vivo evaluation of four synthetic biomaterials with distinct resorption profiles—double-setting alpha-tricalcium phosphate (α-TCPdp), α-TCPdp combined with a lactic-co-glycolic acid and poly(isoprene) copolymer (PLGA/PI), and two 3D-printed polymers, acrylonitrile butadiene styrene (ABS) and polyamide (PA)—for reconstruction of critical-sized mandibular defects in rabbits. Twenty animals were divided into four groups (<i>n</i> = 10 defects each) and evaluated at 30, 60, and 120 days post-implantation through clinical, radiographic, histopathological, and scanning electron microscopy analyses. All implants exhibited excellent biocompatibility, osseointegration, and absence of adverse tissue reactions. ABS and PA promoted significantly greater early bone neoformation compared to α-TCP-based cements, whereas α-TCPdp and α-TCPdp + PLGA/PI underwent gradual bone replacement via surface degradation and creeping substitution. The addition of PLGA/PI reduced the inflammatory response without compromising osteoconductivity. SEM analysis, enhanced by an adapted decalcification protocol, confirmed continuous bone ingrowth and intimate bone–implant contact. This work provides the first direct comparison of α-TCPdp and polymer-based implants in a mandibular critical defect model, highlighting the potential of both absorbable and non-absorbable biomaterials for customized craniofacial reconstruction.</p>\u0000 </div>","PeriodicalId":15269,"journal":{"name":"Journal of biomedical materials research. Part B, Applied biomaterials","volume":"113 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study explores the potential of 3D-printed carbon fiber-reinforced thermoplastic composites, specifically Nylon and PEEK, as advanced materials for medical implants. Fabricated using fused filament fabrication (FFF), these implants were evaluated against conventional Ti-6AL-4V titanium alloy counterparts through a combination of experimental analysis and finite element method (FEM) simulations. The novel designs of discontinuous carbon fiber-PEEK and continuous carbon fiber-Nylon composites exhibited enhanced performance, reducing screw pull-out force by nearly 50% relative to Ti-6AL-4V. Furthermore, the thermoplastic composites demonstrated significantly higher bio-elastic coupling strain energy density (SED), indicating superior capacity to promote bone healing and callus formation. A comprehensive multi-criteria evaluation—including metrics on screw loosening, bone remodeling, and resorption—revealed that the 3D-printed composites outperformed titanium by 33%–65%. These results provide design guidelines for FFF 3D-printed composite implants, offering considerable promise as customizable and effective alternatives to conventional metal implants.
{"title":"Innovative Biomechanical Design and Performance of Carbon Fiber-Thermoplastic Implants via Additive Manufacturing","authors":"Vacharat Thongsumrit, Phorntep Chaitaweepakorn, Pajjittar Kolimart, Khomkrit Pingkarawat, Wares Chancharoen, Sontipee Aimmanee","doi":"10.1002/jbm.b.35682","DOIUrl":"10.1002/jbm.b.35682","url":null,"abstract":"<div>\u0000 \u0000 <p>This study explores the potential of 3D-printed carbon fiber-reinforced thermoplastic composites, specifically Nylon and PEEK, as advanced materials for medical implants. Fabricated using fused filament fabrication (FFF), these implants were evaluated against conventional Ti-6AL-4V titanium alloy counterparts through a combination of experimental analysis and finite element method (FEM) simulations. The novel designs of discontinuous carbon fiber-PEEK and continuous carbon fiber-Nylon composites exhibited enhanced performance, reducing screw pull-out force by nearly 50% relative to Ti-6AL-4V. Furthermore, the thermoplastic composites demonstrated significantly higher bio-elastic coupling strain energy density (SED), indicating superior capacity to promote bone healing and callus formation. A comprehensive multi-criteria evaluation—including metrics on screw loosening, bone remodeling, and resorption—revealed that the 3D-printed composites outperformed titanium by 33%–65%. These results provide design guidelines for FFF 3D-printed composite implants, offering considerable promise as customizable and effective alternatives to conventional metal implants.</p>\u0000 </div>","PeriodicalId":15269,"journal":{"name":"Journal of biomedical materials research. Part B, Applied biomaterials","volume":"113 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145438203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This review evaluates the effect of magnesium (Mg)-doped coatings on the osseointegration of titanium (Ti)-based implants. The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the PRISMA 2020 Statement were followed, with registration in PROSPERO (CRD42024572571). The PICOS strategy was based on population: dental implants; intervention: Mg coatings; control: surfaces without Mg; outcomes: bone–implant contact (BIC), bone area (BA), implant stability coefficient (ISQ), and removal torque (RTQ); and study Design: in vivo studies. The SYRCLE tool was used to assess the risk of bias of animal studies. Meta-analyses were performed, using a random-effect model and 95% confidence interval. Twenty-three records were included, and 21 were enrolled in the meta-analyses. The most commonly used Mg doping method was microarc oxidation. The Mg-doped coatings, significantly favored pooled BIC values in animals [−6.09 (−8.35, −3.82), I2: 50%, p < 0.00001], especially up to 3, 4, 6, and 8 weeks compared to surfaces without Mg. Interestingly, Mg-doped coatings favored BA up to 6 weeks [−8.20 (−14.31, −2.09), I2: 0%, p = 0.008], and RTQ up to 3 [−8.44 (−12.33, −4.56), I2: 63%, p < 0.0001]. Conversely, it did not influence ISQ [−0.24 (−2.05, 1.58), I2: 88%, p = 0.80]. Mg-doped coatings significantly enhanced osseointegration in dental implants by improving BIC, BA, and RTQ, while showing no impact on ISQ. Supported by studies across various animal species, these results confirm that such coatings represent an effective and safe approach for promoting bone integration.
本文综述了镁（Mg）掺杂涂层对钛基种植体骨整合的影响。遵循系统评价和荟萃分析首选报告项目的建议以及PRISMA 2020声明，并在PROSPERO注册（CRD42024572571）。PICOS策略基于人群：种植牙；干预：Mg涂层；控制：不含Mg的表面；结果：骨-种植体接触（BIC）、骨面积（BA）、种植体稳定系数（ISQ）和移除扭矩（RTQ）；研究设计：体内研究。使用sycle工具评估动物研究的偏倚风险。采用随机效应模型和95%置信区间进行meta分析。23条记录被纳入meta分析，21条被纳入meta分析。最常用的Mg掺杂方法是微弧氧化。与不含Mg的涂层相比，Mg掺杂涂层显著有利于动物体内的混合BIC值[- 6.09 (- 8.35,- 3.82),I2: 50%, p < 0.00001]，特别是在3、4、6和8周内。有趣的是，掺杂mg的涂层有利于BA长达6周[- 8.20 (- 14.31,- 2.09),I2: 0%, p = 0.008]， RTQ高达3 [- 8.44 (- 12.33,- 4.56),I2: 63%, p < 0.0001]。相反，对ISQ没有影响[- 0.24 (- 2.05,1.58),I2: 88%, p = 0.80]。mg掺杂涂层通过改善BIC、BA和RTQ显著增强牙种植体的骨整合，而对ISQ没有影响。通过对各种动物物种的研究，这些结果证实了这种涂层是一种有效和安全的促进骨整合的方法。
{"title":"Magnesium-Doped Coatings as a Suitable Approach to Improve Osseointegration of Titanium-Based Implants: A Systematic Review and Meta-Analyses of Animal Studies","authors":"Cícero Andrade Sigilião Celles, Conrado Aparicio, Valentim Adelino Ricardo Barão, Caroline Dini","doi":"10.1002/jbm.b.35681","DOIUrl":"https://doi.org/10.1002/jbm.b.35681","url":null,"abstract":"<p>This review evaluates the effect of magnesium (Mg)-doped coatings on the osseointegration of titanium (Ti)-based implants. The recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the PRISMA 2020 Statement were followed, with registration in PROSPERO (CRD42024572571). The PICOS strategy was based on population: dental implants; intervention: Mg coatings; control: surfaces without Mg; outcomes: bone–implant contact (BIC), bone area (BA), implant stability coefficient (ISQ), and removal torque (RTQ); and study Design: in vivo studies. The SYRCLE tool was used to assess the risk of bias of animal studies. Meta-analyses were performed, using a random-effect model and 95% confidence interval. Twenty-three records were included, and 21 were enrolled in the meta-analyses. The most commonly used Mg doping method was microarc oxidation. The Mg-doped coatings, significantly favored pooled BIC values in animals [−6.09 (−8.35, −3.82), <i>I</i><sup>2</sup>: 50%, <i>p</i> < 0.00001], especially up to 3, 4, 6, and 8 weeks compared to surfaces without Mg. Interestingly, Mg-doped coatings favored BA up to 6 weeks [−8.20 (−14.31, −2.09), <i>I</i><sup>2</sup>: 0%, <i>p</i> = 0.008], and RTQ up to 3 [−8.44 (−12.33, −4.56), <i>I</i><sup>2</sup>: 63%, <i>p</i> < 0.0001]. Conversely, it did not influence ISQ [−0.24 (−2.05, 1.58), <i>I</i><sup>2</sup>: 88%, <i>p</i> = 0.80]. Mg-doped coatings significantly enhanced osseointegration in dental implants by improving BIC, BA, and RTQ, while showing no impact on ISQ. Supported by studies across various animal species, these results confirm that such coatings represent an effective and safe approach for promoting bone integration.</p>","PeriodicalId":15269,"journal":{"name":"Journal of biomedical materials research. Part B, Applied biomaterials","volume":"113 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.b.35681","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145406530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Carolina Chagas, Lais M. Cardoso, Taisa N. Pansani, Carlos A. De-Souza-Costa, Fernanda G. Basso
Failures in oral implant installation may be associated with elevated concentrations of matrix metalloproteinases (MMPs). The overexpression of these enzymes leads to extensive extracellular matrix degradation, delaying or impairing tissue repair. Moreover, their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs), are often insufficient to counteract pathologically elevated MMP levels. To address this, various MMP-regulating strategies have been explored, including the use of flavonoids such as naringenin (NA), a citrus-derived compound with promising anti-inflammatory effects and MMP downregulation. Additionally, surface modifications of titanium (Ti) implants can enhance tissue response and improve osseointegration. This study aimed to characterize and evaluate the effects of Ti surface modification through alkali treatment and NA-laden gelatin methacryloyl (GelMA) coating on osteoblast (Ob) functions related to peri-implant repair in vitro. Ti discs were alkalinized using 5 M sodium hydroxide (NaOH) at 60°C for 24 h. GelMA hydrogel (15% w/v) containing 0% (control) or 1% NA (w/w) was prepared and applied as a coating. The coatings were characterized for morphology, swelling, degradation, and NA release profile. SAOS-2 osteoblasts (HTB-85) were then cultured on the coated discs, and cell adhesion, viability, and synthesis of MMP-2, MMP-9, TIMP-1, and TIMP-2 were assessed. Data were analyzed by one- or two-way ANOVA and Student's t-test/post hoc tests (α = 0.05). Scanning electron microscopy confirmed successful coating, with the GelMA+NA 1% group showing a more uniform and porous surface compared to GelMA alone. Both formulations displayed similar swelling capacity and degradation profiles over 21 days (p > 0.05). NA release was sustained for 14 days, peaking at 15 h. Cell viability and adhesion were comparable between groups (p > 0.05). Osteoblasts cultured on GelMA and exposed to the inflammatory stimulus tumor necrosis factor-alpha (TNF-α) showed increased synthesis of MMP-2, MMP-9, TIMP-1, and TIMP-2. However, cells cultured on GelMA+NA 1% exhibited significantly reduced MMP-2 and MMP-9 levels compared to GelMA under TNF-α stimulation (p < 0.05), with no significant changes in TIMP-1 or TIMP-2. In summary, Ti surface modification through alkali treatment followed by GelMA/NA coating was cytocompatible, showed controlled degradability, sustained NA release, and downregulated MMP synthesis in osteoblasts. These results suggest its potential as a promising strategy to modulate MMPs, which may help mitigate excessive matrix degradation and favor peri-implant tissue repair.
{"title":"Synthesis, Characterization and Feasibility of a Gelatin Methacryloyl Hydrogel for Naringenin Release—Effect on Osteoblasts In Vitro","authors":"Ana Carolina Chagas, Lais M. Cardoso, Taisa N. Pansani, Carlos A. De-Souza-Costa, Fernanda G. Basso","doi":"10.1002/jbm.b.35690","DOIUrl":"https://doi.org/10.1002/jbm.b.35690","url":null,"abstract":"<div>\u0000 \u0000 <p>Failures in oral implant installation may be associated with elevated concentrations of matrix metalloproteinases (MMPs). The overexpression of these enzymes leads to extensive extracellular matrix degradation, delaying or impairing tissue repair. Moreover, their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs), are often insufficient to counteract pathologically elevated MMP levels. To address this, various MMP-regulating strategies have been explored, including the use of flavonoids such as naringenin (NA), a citrus-derived compound with promising anti-inflammatory effects and MMP downregulation. Additionally, surface modifications of titanium (Ti) implants can enhance tissue response and improve osseointegration. This study aimed to characterize and evaluate the effects of Ti surface modification through alkali treatment and NA-laden gelatin methacryloyl (GelMA) coating on osteoblast (Ob) functions related to peri-implant repair in vitro. Ti discs were alkalinized using 5 M sodium hydroxide (NaOH) at 60°C for 24 h. GelMA hydrogel (15% w/v) containing 0% (control) or 1% NA (w/w) was prepared and applied as a coating. The coatings were characterized for morphology, swelling, degradation, and NA release profile. SAOS-2 osteoblasts (HTB-85) were then cultured on the coated discs, and cell adhesion, viability, and synthesis of MMP-2, MMP-9, TIMP-1, and TIMP-2 were assessed. Data were analyzed by one- or two-way ANOVA and Student's <i>t</i>-test/post hoc tests (α = 0.05). Scanning electron microscopy confirmed successful coating, with the GelMA+NA 1% group showing a more uniform and porous surface compared to GelMA alone. Both formulations displayed similar swelling capacity and degradation profiles over 21 days (<i>p</i> > 0.05). NA release was sustained for 14 days, peaking at 15 h. Cell viability and adhesion were comparable between groups (<i>p</i> > 0.05). Osteoblasts cultured on GelMA and exposed to the inflammatory stimulus tumor necrosis factor-alpha (TNF-α) showed increased synthesis of MMP-2, MMP-9, TIMP-1, and TIMP-2. However, cells cultured on GelMA+NA 1% exhibited significantly reduced MMP-2 and MMP-9 levels compared to GelMA under TNF-α stimulation (<i>p</i> < 0.05), with no significant changes in TIMP-1 or TIMP-2. In summary, Ti surface modification through alkali treatment followed by GelMA/NA coating was cytocompatible, showed controlled degradability, sustained NA release, and downregulated MMP synthesis in osteoblasts. These results suggest its potential as a promising strategy to modulate MMPs, which may help mitigate excessive matrix degradation and favor peri-implant tissue repair.</p>\u0000 </div>","PeriodicalId":15269,"journal":{"name":"Journal of biomedical materials research. Part B, Applied biomaterials","volume":"113 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aml Awad, Awad Rizk, Mohamed ElAlfy, Mohamed Hamed, Amr M. Abdelghany, Esam Mosbah, Adel Zaghloul, Gamal Karrouf
<div> <p>Nanomaterials and platelets derivatives provide promising substitutes in regenerative medicine for the management of avascular necrosis of the femoral head (AVN). Thus, this study was accomplished to evaluate the effectiveness of Platelets rich fibrin (PRF) and Hydroxyapatite nanoparticles (HANPs) as innovative strategies for providing immediate mechanical support and protecting the femoral head from collapse in a surgical model of AVN and their influence on optimizing core decompression (CD) via clinical, radiographic, histopathological, and immuno-histochemical analyses. Fifty-six Sprague Dawley rats were divided into four groups. Bipolar electrocoagulation was used to surgically induce AVN by depriving blood flow. HANPs were administered to the ischemic femoral head via CD hole and sealed with PRF gel in the CD-PRF-HANPs treated group, while a CD hole was made and sealed with PRF gel in the CD-PRF treated group. The healing was evaluated at 2- and 8-weeks following surgery clinically, radiographically using Cone beam computed tomography (CBCT), and histopathologically using HE, Masson Trichrome, and Alizarin red S staining's and immunohistochemistry where Osteopontin (OPN) and cluster of differentiation 34 (CD34) were detected. The CD-PRF-HANPs group revealed a significant enhancement in mechanical hyperalgesia compared to the AVN group (<i>p</i> < 0.01) at 2 weeks, with the greatest improvement observed at 8 weeks compared to both AVN (<i>p</i> < 0.0001) and the CD-PRF group (<i>p</i> = 0.0001). It also showed enhanced efficacy in regenerating the ischemic femoral head and maintaining head sphericity, as evidenced by macroscopical images and CBCT measurements. It recorded higher BMD relative to CD-PRF (<i>p</i> = 0.003) at 8 weeks, with complete obliteration of the CD tunnel. In contrast, the AVN group displayed subchondral collapse (crescent sign) at 2 weeks and complete noticeable femoral head deformity, with the lowest CBCT values at 8 weeks (<i>p</i> < 0.0001). Histopathological analysis of the CD-PRF-HANPs group confirmed a significant restoration of normal cortical bone, organized bone lacunae, osteoid matrix, and enhanced mineralization. The AVN group displayed a significant (<i>p</i> < 0.0001) increase in the number of empty lacunae over time, compared to the other groups; in contrast, the CD-PRF-HANPs group demonstrated a significant (<i>p</i> = 0.0005) decrease in the number of empty lacunae compared to the CD-PRF group. Additionally, it exhibited the highest levels of OPN and CD34 (<i>p</i> < 0.0001), indicating a beneficial role in promoting bone matrix deposition, osteogenesis, and angiogenesis, thereby offering enhanced protection and regeneration of the femoral head. In a rat model of AVN, intraosseous administration of HANPs and PRF gel positively influenced the repair of the ischemic femoral head architecture, protected it from accelerated bone turnover, restored joint integrity, and
{"title":"Synergistic Effects of Hydroxyapatite Nanoparticles and Platelet Rich Fibrin on Femoral Head Avascular Necrosis Repair in a Rat Model","authors":"Aml Awad, Awad Rizk, Mohamed ElAlfy, Mohamed Hamed, Amr M. Abdelghany, Esam Mosbah, Adel Zaghloul, Gamal Karrouf","doi":"10.1002/jbm.b.35672","DOIUrl":"10.1002/jbm.b.35672","url":null,"abstract":"<div>\u0000 \u0000 <p>Nanomaterials and platelets derivatives provide promising substitutes in regenerative medicine for the management of avascular necrosis of the femoral head (AVN). Thus, this study was accomplished to evaluate the effectiveness of Platelets rich fibrin (PRF) and Hydroxyapatite nanoparticles (HANPs) as innovative strategies for providing immediate mechanical support and protecting the femoral head from collapse in a surgical model of AVN and their influence on optimizing core decompression (CD) via clinical, radiographic, histopathological, and immuno-histochemical analyses. Fifty-six Sprague Dawley rats were divided into four groups. Bipolar electrocoagulation was used to surgically induce AVN by depriving blood flow. HANPs were administered to the ischemic femoral head via CD hole and sealed with PRF gel in the CD-PRF-HANPs treated group, while a CD hole was made and sealed with PRF gel in the CD-PRF treated group. The healing was evaluated at 2- and 8-weeks following surgery clinically, radiographically using Cone beam computed tomography (CBCT), and histopathologically using HE, Masson Trichrome, and Alizarin red S staining's and immunohistochemistry where Osteopontin (OPN) and cluster of differentiation 34 (CD34) were detected. The CD-PRF-HANPs group revealed a significant enhancement in mechanical hyperalgesia compared to the AVN group (<i>p</i> < 0.01) at 2 weeks, with the greatest improvement observed at 8 weeks compared to both AVN (<i>p</i> < 0.0001) and the CD-PRF group (<i>p</i> = 0.0001). It also showed enhanced efficacy in regenerating the ischemic femoral head and maintaining head sphericity, as evidenced by macroscopical images and CBCT measurements. It recorded higher BMD relative to CD-PRF (<i>p</i> = 0.003) at 8 weeks, with complete obliteration of the CD tunnel. In contrast, the AVN group displayed subchondral collapse (crescent sign) at 2 weeks and complete noticeable femoral head deformity, with the lowest CBCT values at 8 weeks (<i>p</i> < 0.0001). Histopathological analysis of the CD-PRF-HANPs group confirmed a significant restoration of normal cortical bone, organized bone lacunae, osteoid matrix, and enhanced mineralization. The AVN group displayed a significant (<i>p</i> < 0.0001) increase in the number of empty lacunae over time, compared to the other groups; in contrast, the CD-PRF-HANPs group demonstrated a significant (<i>p</i> = 0.0005) decrease in the number of empty lacunae compared to the CD-PRF group. Additionally, it exhibited the highest levels of OPN and CD34 (<i>p</i> < 0.0001), indicating a beneficial role in promoting bone matrix deposition, osteogenesis, and angiogenesis, thereby offering enhanced protection and regeneration of the femoral head. In a rat model of AVN, intraosseous administration of HANPs and PRF gel positively influenced the repair of the ischemic femoral head architecture, protected it from accelerated bone turnover, restored joint integrity, and","PeriodicalId":15269,"journal":{"name":"Journal of biomedical materials research. Part B, Applied biomaterials","volume":"113 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bone tissue exhibits inherent bioelectrical properties, and electrical stimulation (ES) has been demonstrated to effectively accelerate bone healing. However, insufficient attention has been devoted to investigating biocomposite materials that synergize with electrostimulation for bone defect repair. In this study, a composite of strontium-doped hydroxyapatite and chitosan (Sr-HA@CS) was synthesized and demonstrated to promote bone regeneration. Under combined ES, the Sr-HA@CS hydrogel not only exhibited excellent injectability, biocompatibility, and osteoinductivity, but also significantly upregulated osteogenesis-related genes and accelerated the osteogenic process, as revealed by RNA sequencing analysis. This synergistic effect further promoted intracellular calcium enrichment and enhanced bone regeneration in vivo. Therefore, the development of the Sr-HA@CS composite combined with ES therapy holds promise for accelerating bone repair and represents an important area of research.
{"title":"Electrical Stimulation Combined With Hydroxyapatite Hydrogel for Bone Regeneration","authors":"Jingjing Gao, Xue Wang, Ziming Ma, Haichuan Sun, Huilin Hu, Lijia Cheng","doi":"10.1002/jbm.b.35687","DOIUrl":"10.1002/jbm.b.35687","url":null,"abstract":"<div>\u0000 \u0000 <p>Bone tissue exhibits inherent bioelectrical properties, and electrical stimulation (ES) has been demonstrated to effectively accelerate bone healing. However, insufficient attention has been devoted to investigating biocomposite materials that synergize with electrostimulation for bone defect repair. In this study, a composite of strontium-doped hydroxyapatite and chitosan (Sr-HA@CS) was synthesized and demonstrated to promote bone regeneration. Under combined ES, the Sr-HA@CS hydrogel not only exhibited excellent injectability, biocompatibility, and osteoinductivity, but also significantly upregulated osteogenesis-related genes and accelerated the osteogenic process, as revealed by RNA sequencing analysis. This synergistic effect further promoted intracellular calcium enrichment and enhanced bone regeneration in vivo. Therefore, the development of the Sr-HA@CS composite combined with ES therapy holds promise for accelerating bone repair and represents an important area of research.</p>\u0000 </div>","PeriodicalId":15269,"journal":{"name":"Journal of biomedical materials research. Part B, Applied biomaterials","volume":"113 11","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145389175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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