Journal of biomedical materials research. Part A最新文献

{"title":"Enhanced Metabolic Syndrome Management Through Cannabidiol-Loaded PLGA Nanoparticles: Development and In Vitro Evaluation","authors":"Mazen M. El-Hammadi,&nbsp;Lucía Martín-Navarro,&nbsp;Esther Berrocoso,&nbsp;Josefa Álvarez-Fuentes,&nbsp;Benedicto Crespo-Facorro,&nbsp;Irene Suárez-Pereira,&nbsp;Javier Vázquez-Bourgon,&nbsp;Lucía Martín-Banderas","doi":"10.1002/jbm.a.37916","DOIUrl":"https://doi.org/10.1002/jbm.a.37916","url":null,"abstract":"<div>\u0000 \u0000 <p>Cannabidiol (CBD) holds promise for managing metabolic diseases, yet enhancing its oral bioavailability and efficacy remains challenging. To address this, we developed polymeric nanoparticles (NPs), using poly(lactic-co-glycolic acid) (PLGA), encapsulating CBD using nanoprecipitation, aiming to create an effective CBD-nanoformulation for metabolic disorder treatment. These NPs (135–265 nm) demonstrated high encapsulation efficiency (EE% ≈ 100%) and sustained release kinetics. Their therapeutic potential was evaluated in an in vitro metabolic syndrome model employing sodium palmitate-induced HepG2 cells. Key assessment parameters included cell viability (MTT assay), glucose uptake, lipid accumulation (Oil Red O staining), triglycerides, cholesterol, HDL-c levels, and gene expression of metabolic regulators. Results showed an IC50 of 9.85 μg/mL for free CBD and 11.26 μg/mL for CBD-loaded NPs. CBD-loaded NPs significantly enhanced glucose uptake, reduced lipid content, lowered triglycerides and total cholesterol, and increased HDL-c levels compared to free CBD. Gene analysis indicated reduced gluconeogenesis via downregulation of PPARγ, FOXO-1, PEPCK, and G6Pase and enhanced fatty acid oxidation through CPT-1 upregulation. These findings suggest that CBD-loaded NPs may serve as a novel therapeutic strategy for the management of metabolic disorders, warranting further in vivo studies.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871562","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":"Harnessing Thrombospondin-1-Enabled Decellularized Nucleus Pulposus Matrices and Elastin-Like Recombinamers to Rebuild an Avascular Analogue of the Intervertebral Disc","authors":"Carlos Marinho Botelho,&nbsp;José Carlos Rodríguez-Cabello,&nbsp;Mário Adolfo Barbosa","doi":"10.1002/jbm.a.37911","DOIUrl":"https://doi.org/10.1002/jbm.a.37911","url":null,"abstract":"<div>\u0000 \u0000 <p>With the degeneration of the intervertebral disc (IVD), the ingrowth of vascular and neural structures occurs. Both nerves and blood vessels engage in the development of inflammation and the onset of discogenic pain. The present study aimed to produce a hierarchical biomaterial capable of inhibiting angiogenesis by emulating the microenvironment of non-degenerated IVDs. To this end, we have incorporated an angiogenesis modulator—thrombospondin-1 (TSP-1) into a three-dimensional (3D) hydrogel network containing decellularized nucleus pulposus (dNPs) and azide-cyclooctyne modified elastin-like recombinamers (ELRs). Following the decellularization of nucleus pulposus (NPs) isolated from bovine tissues, pre-gels (pGs) were assembled based on the acid-pepsin extraction of soluble collagens found in the dNPs. Given the inherent affinity of these macromolecules to TSP-1, which was corroborated by immunohistochemical analysis and FT-IR spectroscopy, the pGs were supplemented with two concentrations of TSP-1. Angiogenesis was evaluated using the chick chorioallantoic membrane (CAM) in vivo model. Conjugation of TSP-1 with the pGs resulted in a synergistic suppression of blood vessel formation. Complexation with the ELRs improved the viscoelastic moduli and the structural stability of the hydrogels, which maintained their hydration and osmolarity properties due to the presence of the dNPs. When placed in direct contact with human primary fibroblasts, the materials displayed high cytocompatibility and tunable degradation rates. Our findings indicate that TSP-1-enabled dNP-derived pGs inhibit angiogenesis in vivo, while the presence of the ELRs aids in improving the mechanical properties of the hydrogels, thus providing a platform for rebuilding an avascular analogue of the healthy IVD.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865869","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":"Zinc Oxide@Tetracycline Spiky Microparticles Design for Persistent Antibacterial Therapy","authors":"Youjin Seol,&nbsp;Keya Ganguly,&nbsp;Tejal V. Patil,&nbsp;Sayan Deb Dutta,&nbsp;Hyeonseo Park,&nbsp;Jieun Lee,&nbsp;Aayushi Randhawa,&nbsp;Hojin Kim,&nbsp;Ki-Taek Lim","doi":"10.1002/jbm.a.37915","DOIUrl":"https://doi.org/10.1002/jbm.a.37915","url":null,"abstract":"<p>Antibiotics have revolutionized medical treatment by effectively combating bacterial infections, particularly those associated with chronic wounds and implant complications. Nevertheless, the persistent use of these drugs has resulted in an increase in antibiotic-resistant bacteria and biofilm infections, highlighting the urgent need for alternative therapies. This study presents an approach for combating persistent bacterial and biofilm infections through the integration of biomimetic design and advanced nanotechnology. Inspired by the natural defense mechanisms of pollen grains and lotus leaves, we engineered zinc oxide spiky microparticles combined with tetracycline-loaded beads mimicking the structure of lotus leaf papillae. This biomimetic design exhibits a multifaceted antimicrobial strategy, leveraging hierarchical micro/nanostructures and the inherent antibacterial properties of their natural counterparts. ZnO microparticles, which mimic the morphology of pollen grains, provide topological cues to rupture adhered bacteria, whereas tetracycline beads, inspired by lotus leaf papillae, deliver a controlled release of antibiotics to target persistent bacteria. Using a synergistic multimodal approach, our biomimetic materials demonstrated exceptional efficacy in eradicating persistent methicillin-resistant <i>Staphylococcus aureus</i> and <i>Escherichia coli</i> infections, offering promising prospects for the development of advanced antibacterial therapies. This study not only underscores the importance of biomimicry in material design but also highlights the potential of integrating nature-inspired strategies with nanotechnology for biomedical applications.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37915","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanofibrous GelMA-Based Scaffolds Support Human Adipose-Derived Mesenchymal Stem/Stromal Cell Adhesion, Viability, and Growth","authors":"Lautaro Rivera,&nbsp;Matthäus Davi Popov Pereira da Cunha,&nbsp;Rocío Jazmín Sabbatella,&nbsp;Samanta del Veliz,&nbsp;Gustavo Abel Abraham,&nbsp;Marina Uhart,&nbsp;Ana Agustina Aldana","doi":"10.1002/jbm.a.37914","DOIUrl":"https://doi.org/10.1002/jbm.a.37914","url":null,"abstract":"<div>\u0000 \u0000 <p>Drawing inspiration from the extracellular matrix (ECM), where fiber organization profoundly influences cell behavior, electrospun scaffolds have emerged as powerful tools for modulating cellular responses in vitro. While electrospinning enables the replication of ECM architecture, selecting suitable materials is paramount for effective cell adhesion and growth. In this study, we aimed to develop cost-effective scaffolds for human adipose-derived mesenchymal stromal cells (hAD-MSCs) using gelatin methacrylate (GelMA) blended with either polycaprolactone (PCL) or poly(ethylene glycol) dimethacrylate (PEGDMA). Through comparing randomly oriented and aligned fibers, we identified fiber direction as a critical factor in determining cell behavior. Surprisingly, we found that despite material hydrophobicity, the cells aligned with the fiber direction, highlighting the dominant influence of fiber alignment on cell spreading. This research underscores the importance of material selection and fiber orientation in engineering scaffolds for directing cell behavior in tissue regeneration applications.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856787","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":"Advances in Bacterial Cellulose-Based Scaffolds for Tissue Engineering: Review","authors":"Rewati Raman Ujjwal,&nbsp;Gymama Slaughter","doi":"10.1002/jbm.a.37912","DOIUrl":"https://doi.org/10.1002/jbm.a.37912","url":null,"abstract":"<p>Bacterial cellulose (BC) has emerged as a highly versatile and promising biomaterial in tissue engineering, with potential applications across skin, bone, cartilage, and vascular regeneration. Its exceptional properties like high mechanical strength, superior biocompatibility, excellent moisture retention, and inherent ability to support cell adhesion and proliferation, make BC particularly effective for wound healing and skin regeneration. These attributes accelerate tissue repair and foster new tissue formation, highlighting its value in skin-related applications. Additionally, BC's capacity to support osteogenic differentiation, combined with its mechanical robustness, positions it as a strong candidate for bone tissue engineering, facilitating regeneration and repair. Recent advancements have emphasized the development of BC-based hybrid scaffolds to enhance tissue-specific functionalities, including vascularization and cartilage regeneration. These innovations aim to address the complex requirements of various tissue engineering applications. However, challenges remain, particularly regarding the scalability of BC production, cost-effectiveness, and the long-term stability of BC-based scaffolds. Such barriers continue to limit its broader clinical adoption. This review critically examines the synthesis methods, intrinsic properties, and recent innovations in the design of BC-based scaffolds, offering insights into their potential to revolutionize regenerative medicine. Furthermore, it addresses the key challenges and limitations that must be overcome to enable the clinical integration of BC. By addressing these limitations, BC could play a transformative role in advancing tissue engineering and regenerative therapies, bridging the gap between laboratory research and clinical application.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37912","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Dysregulated Epigenetic Modifiers With Kidney-Targeted Nanotherapeutics for Polycystic Kidney Disease","authors":"Joshua Giblin,&nbsp;Rowan Simon,&nbsp;Jose Zarate-Diaz,&nbsp;Brenton Lee,&nbsp;Eun Ji Chung","doi":"10.1002/jbm.a.37909","DOIUrl":"https://doi.org/10.1002/jbm.a.37909","url":null,"abstract":"<div>\u0000 \u0000 <p>Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease worldwide. The one small molecule drug available to patients, tolvaptan, is associated with off-target side effects and high discontinuation rates, necessitating the development of new therapeutic strategies. Previous work has shown that the epigenome is altered in ADPKD; however, the identification and targeting of dysregulated epigenetic modulators has yet to be explored for human ADPKD therapy. Using cells derived from cysts of ADPKD patients, we tested the gene expression of several epigenetic modulators. We found Brd4 and BMi1 are upregulated and observed that their inhibition using small molecule drugs, AZD-5153 and PTC-209, significantly slowed the proliferation of ADPKD patient cells. To enhance the delivery of AZD-5153 and PTC-209 to renal cells, we loaded the drugs into kidney-targeting micelles (KM) and assessed their therapeutic effects in vitro. Combining AZD-5153 and PTC-209 in KMs had a synergistic effect on reducing the proliferation in ADPKD patient cells and in a 3D PKD cyst model. These findings were also consistent in murine in vitro models using Pkd1 null renal proximal tubule cells. In summary, we demonstrate Brd4 and BMi1 as novel targets in ADPKD and targeting the epigenome using kidney nanomedicine as a novel therapeutic strategy in ADPKD.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801722","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":"Sub-Micrometer Polycaprolactone and Polyethylene Glycol-Based Fiber Mats With Iodine and Its Potential for Wound Healing","authors":"Agnes Chacor de Figueiredo,&nbsp;Bruna Nunes Teixeira,&nbsp;Javier Mauricio Anaya-Mancipe,&nbsp;Verônica Silva Cardoso,&nbsp;Alane Beatriz Vermelho,&nbsp;Rossana Mara da Silva Moreira Thiré","doi":"10.1002/jbm.a.37913","DOIUrl":"https://doi.org/10.1002/jbm.a.37913","url":null,"abstract":"<p>This study introduces an innovative approach to developing advanced antimicrobial wound dressings by engineering fiber mats of polycaprolactone (PCL) and polycaprolactone/polyethylene glycol (PCL/PEG) loaded with iodine using solution blow spinning (SBS). The mats exhibited a unique morphology, combining fibers and beads, with average fiber diameters of 570 nm for 12% (w/v) PCL and 470 nm for 1% (w/v) PEG in 12% (w/v) PCL, and bead diameters of 11.34 μm and 10.43 μm, respectively. PEG incorporation rendered the mats hydrophilic and significantly enhanced their swelling capacity, which is essential for wound exudate management. Remarkably, iodine was incorporated at a concentration specifically optimized to achieve its minimum inhibitory concentration (MIC) against a range of microorganisms while preserving the structural integrity and release profile of the mats. While PEG facilitated a higher initial iodine release rate, equilibrium was achieved after 5 days. UV–Vis spectroscopy unveiled the formation of transient iodine complexes with both PCL and PEG, underscoring their functional synergy. Biological assays revealed that PCL/PEG mats loaded with 4.26 mg/mL of iodine (PCL/PEG 3MIC) exhibited potent antimicrobial efficacy against gram-positive and gram-negative bacteria, as well as fungi, alongside significant in vitro wound healing potential. These findings underscore the promise of PCL/PEG iodine-loaded mats as an innovative platform for next-generation antimicrobial wound care, combining effective infection control with enhanced wound healing capabilities.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37913","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional Pluronic F-127 Gels Loaded With PEDF, Tacrolimus, and Tobramycin for Advanced Corneal Disease Treatment","authors":"Jing Yu,&nbsp;Xiaojia Hu,&nbsp;Yu Niu,&nbsp;Zhengya Li,&nbsp;Cuicui Tang,&nbsp;Junling Yang,&nbsp;Jinyan Peng,&nbsp;Gang Chen,&nbsp;Liyuan Xing,&nbsp;Lianghong Peng","doi":"10.1002/jbm.a.37907","DOIUrl":"https://doi.org/10.1002/jbm.a.37907","url":null,"abstract":"<div>\u0000 \u0000 <p>Corneal transplantation is a common surgical procedure for restoring vision in patients with severe corneal diseases. However, post-operative complications, including inflammation, immune rejection, and fibrosis, pose significant challenges to the long-term success of corneal transplants. This study aims to develop and evaluate new composite ophthalmic gels combining Tobramycin, Tacrolimus, and pigment epithelium-derived factor (PEDF) for enhancing post-transplant recovery. Four formulations—Tobramycin/PF127, Tobramycin/PEDF/PF127, Tobramycin/Tacrolimus/PF127, and Tobramycin/PEDF/Tacrolimus/PF127 were prepared and evaluated for their effects on human corneal epithelial cells (HCE-T) and human umbilical vein endothelial cells (HUVECs). Cytotoxicity assays revealed that PEDF-containing gels significantly promoted HCE-T cell proliferation and migration, while Tacrolimus exhibited strong immunosuppressive properties, reducing immune activation and promoting a stable healing environment. Additionally, PEDF demonstrated potent anti-angiogenic effects, suppressing tube formation in HUVECs. A 60-day rabbit corneal transplantation model further confirmed the therapeutic potential of the composite gels. Gels containing PEDF and Tacrolimus significantly improved corneal transparency, reduced inflammation and fibrosis, and minimized immune rejection. These findings suggest that Tobramycin/PEDF/Tacrolimus/PF127 gel holds promise as an advanced post-operative treatment, offering a comprehensive approach to addressing the challenges of corneal transplant recovery by enhancing cell proliferation, reducing immune responses, and preventing fibrosis and angiogenesis.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787072","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":"Extracellular Fibronectin and Hyaluronic Acid Effects on Tumorigenic Functions of Triple-Negative Breast Cancer Cells","authors":"Jacob Heiss,&nbsp;Nina Treacher,&nbsp;Astha Lamichhane,&nbsp;Anju Rana Magar,&nbsp;Hossein Tavana","doi":"10.1002/jbm.a.37906","DOIUrl":"https://doi.org/10.1002/jbm.a.37906","url":null,"abstract":"<p>The extracellular matrix (ECM) in solid tumors provides structural support and signaling cues to cancer cells. Altered ECM in tumors promotes local invasion of cancer cells, a key step toward metastasis. Engineered tumor models that are used to study cancer invasion often focus on the effects of an individual ECM molecule on specific functions of cancer cells. However, how different components of ECM in a complex tumor model may co-regulate cancer invasion and the underlying signaling pathways is understudied. We developed a 3D tumor model of triple-negative breast cancer (TNBC) to study the effects of fibronectin and hyaluronic acid, alone or in combination, on TNBC cell invasion of collagen-based hydrogels. Our focus on these molecules was due to their significance in breast tumors, disease progression, and association with worse outcomes in patients. Results showed that fibronectin and hyaluronic acid significantly increase collagen invasion of TNBC cells and oncogenic signaling but not in combination, potentially due to differences in the microstructure of the hydrogels. Fibronectin and hyaluronic acid in composite hydrogels also promoted drug resistance and cancer stemness. This study demonstrated the utility of a 3D tumor model for functional and mechanistic studies to define complex effects of ECM in solid cancers.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37906","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-Functional Peptide DPI-VTK Promotes Mesenchymal Stem Cell Migration for Bone Regeneration","authors":"Eric J. Madsen,&nbsp;Seungmeen Rhee,&nbsp;Madison Wahlsten,&nbsp;Tia C. Calabrese,&nbsp;David H. Kohn","doi":"10.1002/jbm.a.37908","DOIUrl":"https://doi.org/10.1002/jbm.a.37908","url":null,"abstract":"<p>Targeting specific populations of host cells with chemotactic and adhesion factors is a promising strategy for inducing bone regeneration without the use of exogenous cells. Two peptide sequences have been derived from phage display: the mesenchymal stem cell (MSC) binding DPI (DPIYALSWSGMA) sequence and the apatite binding VTK (VTKHLNQISQSY) sequence. When combined into the dual-functional sequence, DPI-VTK increases the adhesion strength of MSCs to apatite surfaces and the amount of bone formation with transplanted MSCs. Because many adhesion molecules can stimulate chemotaxis, and cell adhesion to peptide DPI-VTK is mediated by integrins also critical to migration, we hypothesized that DPI-VTK serves as an MSC-specific chemotactic factor and can increase bone regeneration by promoting the osteogenesis of the migrated host MSCs in vivo. In transwell assays, induced pluripotent stem cell-derived human MSCs (<i>p</i> &lt; 0.0001) and primary mouse calvarial cells (<i>p</i> &lt; 0.0001) showed significantly increased migration in vitro when DPI-VTK was used as a chemoattractant. Further characterization of DPI-VTK binding cells from mouse calvaria using flow cytometry showed specificity toward cells expressing MSC markers (CD29, CD73, CD90, CD105, CD106, Sca-1, CD44, and CD200). When conjugated to a mineralized scaffold in vivo, DPI-VTK increased the migration of CD90 and CD200 positive cells (<i>p</i> &lt; 0.05) and increased bone formation versus no-peptide controls (<i>p</i> &lt; 0.05). These results demonstrate the utility of phage display in creating multifunctional peptides that can increase migration, adhesion, and bone formation in vivo, a strategy that could be applied to numerous different cell types and systems. Results advance biomaterials-based bone regeneration in two ways—demonstrating the ability of the phage-derived peptides to increase the migration of MSCs in vivo and increase host-mediated bone regeneration—potentially bypassing cell transplantation.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37908","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778326","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}