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J Biomed Mater Res A [JOURNAL]

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Enhancing the Potency of Growth Factor-Mimicking Peptides via Cross-Presentation With Integrin Ligands.

Neal S, Tan X, Jain E … +4 more , Chen C, Hashemi M, Setton LA, Huebsch N

J Biomed Mater Res A · 2025 Jul · PMID 40552506 · Full text

Growth factors enhance survival and integration of transplanted Mesenchymal Stromal Cells (MSC), but successful supplementation often requires supraphysiological growth factor doses, risking off-target effects. Short pep... Growth factors enhance survival and integration of transplanted Mesenchymal Stromal Cells (MSC), but successful supplementation often requires supraphysiological growth factor doses, risking off-target effects. Short peptide mimics like the knuckle epitope (KE) of Bone Morphogenetic Protein 2 (BMP-2) can be covalently immobilized to biomaterials, localizing bioactivity at the delivery site. However, these short peptides often lack the potency of full-length growth factors. We sought to improve the potency of alginate-grafted KE to encourage MSC osteogenic differentiation. When alginate gels co-presented KE and integrin-binding cyclo-RGD (cRGD) peptides, MSC expressed early markers of osteogenesis (Runt-related Transcription Factor2, RUNX2, Alkaline Phosphatase, ALP, and osteocalcin, OCN) in a KE-dose dependent manner. When co-presented with cRGD, high concentrations of KE partially mimicked the osteogenic potential (ALP induction) of full-length BMP-2. Proximity between KE and cRGD may be the mechanism through which high dose KE induces osteogenesis in the presence of cRGD. To investigate this possibility, we used orthogonal strain-promoted azide-alkyne cycloaddition (SPAAC) and maleimide-thiol chemistries to graft KE and cRGD in a bivalent (same alginate chain) and a monovalent (different alginate chain) manner, at constant bulk peptide concentration. Bivalent presentation of peptides (separation distance of 5.5 ± 0.5 nm verified by FRET) ultimately increased RUNX2 and ALP expression compared to monovalent presentation. This platform technology can be used in future studies to control peptide nanopatterning to enhance potency, in the context of MSC-based therapies and beyond.

Coaxial Bioprinting of Schwann Cells and Neural Stem Cells in a Three-Dimensional Microenvironment for the Repair of Peripheral Nerve Defects.

Wang X, Xu T, Wang F

J Biomed Mater Res A · 2025 Jul · PMID 40552480 · Publisher ↗

Currently, autologous nerve (AN) transplantation remains the gold standard for treating peripheral nerve injuries (PNIs). However, its inherent limitations, including donor site morbidity and immune rejection risks assoc... Currently, autologous nerve (AN) transplantation remains the gold standard for treating peripheral nerve injuries (PNIs). However, its inherent limitations, including donor site morbidity and immune rejection risks associated with allografts, have prompted the exploration of alternative therapeutic strategies. Among these, tissue engineering approaches have gained significant attention, with nerve conduit design emerging as a particularly promising research direction. Electrospinning technology has been widely adopted for its ability to fabricate nanofibrous scaffolds that closely mimic the native extracellular matrix. In this study, we engineered an aligned nanofiber conduit utilizing polylactic acid and gelatin through electrospinning, and integrated a sodium alginate hydrogel enriched with Schwann cells (SCs) and neural stem cells (NSCs) via coaxial bioprinting. The three-dimensional (3D) hydrogel microenvironment facilitated synergistic interactions between SCs and NSCs, augmenting the secretion of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). A dynamic perfusion culture system was further employed to optimize cell viability and functionality. In vivo studies revealed that the implantation of this conduit in a sciatic nerve defect model markedly enhanced motor function recovery, nerve regeneration, and muscle morphology. These improvements were substantiated by an increased sciatic functional index (SFI), heightened expression of S-100 and NF-200, and greater myelin thickness and axon diameter. Although the efficacy of the 3D-aligned nanofiber conduit cocultured with SCs and NSCs approximated that of AN transplantation, further research is imperative to identify more efficient seed cells and biocompatible 3D carriers to achieve optimal nerve regeneration. This study highlights the potential of tissue-engineered nerve conduits as a viable alternative for PNI repair, paving the way for future advancements in the field.

Tendon-Tissue Derived Monofilaments by Electrochemical Compaction: Production and Characterization.

McClellan P, Choi J, Nasrallah M … +2 more , Lundberg K, Akkus O

J Biomed Mater Res A · 2025 Jun · PMID 40524286 · Publisher ↗

Repair of tendon tissues remains a complex problem in orthopedic surgery. Tendon auto- and allografts are not utilized to the full extent of their capabilities due largely to the lack of porosity and availability of prop... Repair of tendon tissues remains a complex problem in orthopedic surgery. Tendon auto- and allografts are not utilized to the full extent of their capabilities due largely to the lack of porosity and availability of properly processed tendon stock. Cryomilling is often utilized to maximize surface area-to-volume while limiting alterations to native protein/gene structure. In this study, native tendons were isolated, cryomilled, and decellularized using a truncated protocol. The resulting decellularized tendon powder exhibited reduced DNA content of less than 15 ng/mg, indicating effective removal of cellular components. The resulting decellularized tendon "powder" was then subjected to mild acidic conditions to partially solubilize the collagen within the extracellular matrix to produce a solution that could be electrochemically compacted to generate aligned fibers. Proteomic analyses revealed the presence of tendon-related proteins (cartilage oligomeric protein, fibromodulin, lumican, biglycan, and tenascin c). Proteoglycans were present in tendon-derived thread (TDT) and largely absent in pure collagen threads, as visualized by safranin O and quantified by dimethylmethylene blue staining. Mesenchymal stem cells seeded and cultured for up to 14 days on collagen threads and TDTs exhibited similar expression of genes related to tendon tissue.

Electrochemical Assessment of the Galvanic Corrosion and Metal Ion Release in Overlapping Stent and Vascular Plug Systems.

Istanbullu OB, Akdogan G, Yilmaz H … +1 more , Istanbullu M

J Biomed Mater Res A · 2025 Jun · PMID 40522074 · Publisher ↗

Cardiovascular diseases cause the highest global mortality rates and are often treated with surgical interventions such as stent or vascular plug placement. However, in-stent restenosis develops over time depending on th... Cardiovascular diseases cause the highest global mortality rates and are often treated with surgical interventions such as stent or vascular plug placement. However, in-stent restenosis develops over time depending on the material composition and interactions with body fluids. Current strategies to address restenosis include balloon angioplasty or placing a secondary stent at the same site. A key concern with overlapping stents is the increasing risk of galvanic corrosion, as most cardiovascular stents have metallic composition. This study examines galvanic corrosion rates in different vascular stent and plug combinations using electrochemical corrosion characterization techniques. Three metallic vascular specimens with varying compositions are evaluated. The specimens are immersed in simulated body fluid at 37°C under individual and overlapping conditions. Electrochemical impedance spectroscopy and current density measurements, conducted via potentiostat, provide insights into the corrosion behavior of each specimen configuration. Additionally, inductively coupled plasma mass spectrometry quantifies metal ion release through SBF samples. Results show that combining dissimilar materials in overlapping placements significantly increases galvanic corrosion and metal ion release. The corrosion current density (i) significantly increased from 11.75 μA/cm in the individual bare-metallic stent to 522.3 μA/cm in the stent-on-plug configuration. A similar increase was observed in the stent-on-stent configuration, with an i of 132.6 μA/cm. These results corresponded with notable decreases in electrochemical impedance and polarization resistance, measured as low as 0.039 kΩ (Z) and 0.057 kΩ cm (R) for the stent-on-plug system. Consequently, the calculated corrosion rate escalated to 2254 μm/year, with a mass loss reaching 42.22 mg/cm·year. ICP-MS analysis supported these findings, showing the highest levels of metal ion release in the stent-on-plug configuration, with 23.86 ppm of Ni and 0.41 ppm of Cr. These findings highlight the importance of stent-material selection in reducing corrosion-related complications. Implementing material-specific strategies in secondary stent placement can lower the risks of inflammatory host response, stent failure, and their long-term effects.

Exploring the Reactions Induced by Bioactive Glass Air Abrasion of Titanium and Their Effects on Osteoblast Cellular Responses.

Abushahba F, Stiller A, Mohamad SA … +5 more , Areid N, Hupa L, Heino TJ, Vallittu PK, Närhi TO

J Biomed Mater Res A · 2025 Jun · PMID 40522065 · Publisher ↗

This study investigated the chemical events that occur when titanium (Ti) surfaces are treated with air particle abrasion (APA) using zinc-containing bioactive glass (ZnBG), followed by immersion in simulated body fluid... This study investigated the chemical events that occur when titanium (Ti) surfaces are treated with air particle abrasion (APA) using zinc-containing bioactive glass (ZnBG), followed by immersion in simulated body fluid (SBF) for up to 96 h. The impact of these changes on osteoblast cell viability, adhesion, and differentiation was evaluated. Sandblasted and acid-etched (SA) Ti disks were subjected to APA with ZnBG particles and then immersed in SBF from 8 to 96 h. Ion dissolution and characterization of ZnBG powder and Ti disks were conducted. Analyses of osteoblast viability, adhesion, and alkaline phosphatase (ALP) activity were performed on MC3T3-E1 cells cultured on control disks (SA-Ti), as well as on ZnBG abraded disks (APA-Ti) and disks immersed for 96 h in SBF (CaP-Ti). After SBF immersion, the ZnBG particle surfaces showed a rise in Si atomic (at.)% within the first 8 h, while Ca remained stable, and the P doubled over 96 h. The ZnBG covering the disks dissolved during the first 8 h, and then the Ca, P, and Si at.% increased as the immersion time extended. The glass particles exhibited amorphous calcium-phosphate (Ca-P) layer formation after 96 h. A significantly (p = 0.004) higher cell viability level was observed on day 7 on APA-Ti compared to SA-Ti disks, while no differences in osteoblast differentiation were observed across the different surfaces. Fluorescence images demonstrated that on day 3, cells adhered to valleys and peaks of CaP-Ti threads but only to valleys on SA-Ti and APA-Ti disks. By day 7, cells were also observed on APA-Ti peaks but not on SA-Ti. In summary, APA enhanced osteoblast proliferation, and a biocompatible Ca-P layer, which formed upon mineralization, supported osteoblast viability, adhesion, and spreading.

Tyrosine-Derived Polymeric Surfactants Modulate the Fusion of Normal and Cancer Cells.

Devore DI, Sun D, Tadmori I … +3 more , Le KN, Lima MRN, Kohn J

J Biomed Mater Res A · 2025 Jun · PMID 40522013 · Publisher ↗

Plasma membrane fusion and resealing play essential roles in diverse biological processes, including embryogenesis, morphogenesis, tissue repair, and cancer metastasis. Certain polymeric surfactants, including poly(ethyl... Plasma membrane fusion and resealing play essential roles in diverse biological processes, including embryogenesis, morphogenesis, tissue repair, and cancer metastasis. Certain polymeric surfactants, including poly(ethylene glycol) (PEG) and triblock poly(alkylene oxides) like Poloxamer 188 (P188), are known to modify cell membrane biophysical properties. This has enabled applications such as PEG fusion for severed nerves and P188-mediated muscle tissue repair. Similar to P188, tyrosine-derived triblock copolymers (TyPS) form self-assembled nanospheres that can reversibly insert into phospholipid monolayers and cell plasma membranes. The effects of phospholipid head group polarity on the insertion of TyPS into Langmuir phospholipid monolayers are examined here. The hydrophobic blocks of the polymeric surfactants are found to provide the primary driving force for insertion in the phospholipid membranes. The impact of the TyPS, PEG, and P188, alone and in combination, on membrane fusion in normal (L929 mouse fibroblast) and transformed (MDA-MB-231 human breast cancer) cells is then determined using in vitro cell culture methods. The cell culture studies demonstrate that PEG induces fusion in both cell lines and reveal that the combination of PEG and P188 has a strong positive synergistic effect on cell fusion. In contrast, the TyPS exhibits strong anti-fusion properties, inhibiting both spontaneous and PEG-enhanced fusion. P188 has a weak antifusion effect compared to TyPS. The fusogenic or antifusogenic behaviors of the polymeric surfactants correlate with their thermodynamic Hansen solubility parameters, and the synthetic tunability of the TyPS enables access to a far greater range of hydrophobicities than the available commercial Poloxamers. These findings suggest that mixtures of PEG and P188 may have the potential to enhance tissue repair and hybridoma output for monoclonal antibody production, while the TyPS may have the potential to inhibit metastatic cancers.

Preparation and Characterization of AgNWs Conductive Hydrogel With High Mechanical Performance, High Electrical Conductivity, and Biocompatibility.

Guan S, Wang F, Wen C … +2 more , Liu H, Sun C

J Biomed Mater Res A · 2025 Jun · PMID 40515632 · Publisher ↗

Hydrogel scaffolds incorporating conductive fillers have garnered significant interest due to their potential applications in neural tissue repair and regenerative medicine. However, most conductive fillers have adverse... Hydrogel scaffolds incorporating conductive fillers have garnered significant interest due to their potential applications in neural tissue repair and regenerative medicine. However, most conductive fillers have adverse effects on the mechanical properties of hydrogel networks. In the present study, a novel polyacrylamide/alginate (PAAm/Alg) assembled with conductive silver nanowires (AgNWs) composite hydrogel was developed through photopolymerization and crosslinking methods. The chemical structure, morphology, mechanical properties, conductivity, porosity, swelling rate, adhesive strength, thermal stability, in vitro biodegradation, and biocompatibility of the prepared hydrogel samples were investigated. The PAAm/Alg-AgNWs hydrogels exhibited uniform pore structure distribution, high porosity and water absorption, improved mechanical and conductive properties, good thermal stability, and adequate biodegradability. In particular, the 0.4 wt% AgNWs conductive hydrogel exhibited excellent conductivity of 0.618 S/m and a high Young's modulus of 43.6 kPa, along with good electrical durability and stability over ten cyclic loading. Moreover, the abundant hydrophilic groups in the hydrogel make it have good adhesion properties at different interfaces. Compared with the PAAm/Alg hydrogel, the incorporation of AgNWs enhanced the material's roughness, facilitating cell adhesion, viability, and proliferation. These results showed that the AgNWs assembled into the PAAm/Alg polymers endowed the hydrogel with high electrical conductivity, while excellent mechanical strength and biocompatibility, indicating an attractive conductive substrate for further studies on neural tissue repair and regeneration.

Synthesis and Evaluation of Mesoporous Silica-Biopolymer-Based Bone Substitutes for Tissue Engineering.

Echazu MIÁ, Renou SJ, Olivetti CE … +3 more , Alvarez GS, Desimone MF, Olmedo DG

J Biomed Mater Res A · 2025 Jun · PMID 40511501 · Publisher ↗

Bone substitutes for tissue regeneration should provide an appropriate environment for cell attachment, differentiation, proliferation, and migration. 3D structure, degradability, swelling, porosity, and cytotoxicity hav... Bone substitutes for tissue regeneration should provide an appropriate environment for cell attachment, differentiation, proliferation, and migration. 3D structure, degradability, swelling, porosity, and cytotoxicity have been highlighted as key points in their design. For this research, mesoporous silica-biopolymer composites were synthesized from mesoporous silica (Mes-Si) particles combined with either collagen (C/Mes-Si) or chitosan (CS/Mes-Si). The composites were evaluated for tissue engineering purposes, as bone substitutes intended to imitate features of the natural bone matrix, thereby providing an appropriate biochemical environment for bone repair. Physicochemical-biological evaluation was performed to identify the features that would be useful for bone tissue engineering. For the Mes-Si particles, the specific surface area was 750.95 m/g and the average pore size was 3.47 nm. SEM images showed that Mes-Si particles were distributed within the chitosan (CS) or collagen (C) matrix. Both composites swelled rapidly and had low cytotoxicity. Histologically, no acute inflammatory infiltrate or giant multinucleated cell was observed 14 days after implantation. In C/Mes-Si, newly woven bone tissue and areas of osseointegration at the C/Mes-Si-tissue interface were observed. In CS/Mes-Si, only reparative granulation tissue was observed. The physicochemical properties and biocompatibility of both composites were adequate for a bone scaffold. Moreover, Mes-Si particles have a tunable surface area for chemical modifications and anchoring bioactive materials, which may enhance composite bioactivity or the delivery of bioactive materials.

Functional Nanoparticle-Enhanced Silk Hydrogels for Tissue Engineering Biomaterials.

Foster OK, Hiscox D, Shaidani S … +5 more , Park J, Canas E, Jacobus C, Patten R, Kaplan DL

J Biomed Mater Res A · 2025 Jun · PMID 40511483 · Publisher ↗

Hydrogels prepared from natural polymers, such as silk fibroin, are useful in the field of tissue engineering due to their biocompatibility, biodegradability, and biological performance. However, poor mechanical properti... Hydrogels prepared from natural polymers, such as silk fibroin, are useful in the field of tissue engineering due to their biocompatibility, biodegradability, and biological performance. However, poor mechanical properties can limit their broader utility. This study investigated reinforcing enzymatically crosslinked silk hydrogels with 130 nm silk nanoparticles (SNPs) to generate silk-silk composite materials with tunable strength and stiffness. The strength of the materials was dependent on SNP concentration, and hydrogels with Young's moduli of 14, 34, and 67 kPa were fabricated by adding no SNPs, 2 mg/mL SNPs, and 4 mg/mL SNPs, respectively. These methods were applied to silk bioinks using Freeform Reversible Embedding of Suspended Hydrogels (FRESH) 3D printing to fabricate complex 3D structures with control of elasticity and modulus. Cylinders with Young's moduli of 17, 35, and 58 kPa were obtained with no SNPs, 2 mg/mL SNPs, and 4 mg/mL SNPs, respectively. SNPs were also preloaded with epidermal growth factor (EGF), relevant for tissue development and wound healing, and sustained release was achieved for over 15 days when embedded in hydrogels. Pilot studies of dermal fibroblast encapsulation in SNP-reinforced silk hydrogels demonstrated cytocompatibility. Tunable silk hydrogels reinforced with SNPs provide application-specific scaffolding for a variety of biomaterial and tissue engineering applications.

Microsphere-Mediated Sustained Delivery of Growth Factors Stimulates Osteogenesis in Target Cells in a Three-Dimensional Microenvironment.

Holkar K, Pethe P, Kale V … +1 more , Ingavle G

J Biomed Mater Res A · 2025 Jun · PMID 40499148 · Publisher ↗

Efficient bone repair relies on both osteogenic and angiogenic signals, with growth factors playing a pivotal role. Despite decades of recognition of their therapeutic potential, the optimal dosages and delivery routes o... Efficient bone repair relies on both osteogenic and angiogenic signals, with growth factors playing a pivotal role. Despite decades of recognition of their therapeutic potential, the optimal dosages and delivery routes of growth factors still require extensive investigation. Previous research demonstrated the osteoinductive and angiogenic potential of growth factors. However, effective therapeutic outcomes depend on precise dosing and prolonged delivery. This study investigates the dual delivery of key growth factors, bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF), providing insights into their optimal dosages and delivery mechanisms. The combination of these growth factors may enhance scaffold-mediated bone regeneration in the early stages of healing. This study employed a dual delivery system using BMP-2 and VEGF, comparing two methods to determine the optimal dosage and delivery strategy. The combined effect indicates that sustained delivery is a more efficient method. Osteogenesis and angiogenesis were examined in an interpenetrating network (IPN) hydrogel composed of alginate and polyethylene diacrylate (PEGDA), which encapsulated preosteoblast MC3T3 cells. The findings of this study reveal significant increases in alkaline phosphatase (ALP) activity and calcium content, emphasizing the effectiveness of this approach. Biomaterial characterization, including swelling measurements, Fourier transform infrared (FTIR) spectroscopy, confirmed growth factor encapsulation, and a release assay validated the delivery process. Compared to direct delivery, sustained delivery increased ALP activity and calcium release by up to 1.12- and 1.85-fold, respectively. Molecular studies indicated that sustained delivery of both growth factors had a stronger osteoinductive and angiogenic effect than direct delivery. This research evaluates the effects of growth factor delivery in a 3D hydrogel-based microenvironment using hydrogels and compares delivery methods to identify a more effective strategy for bone healing.

Designing Next-Generation Biomaterials to Enhance Peripheral Nerve Repair and Reconstruction.

Putman R, Li N, Joh DY … +4 more , Roberts S, Pidgeon T, Mithani S, Chilkoti A

J Biomed Mater Res A · 2025 Jun · PMID 40495454 · Publisher ↗

Peripheral nerve injuries are a common and potentially devastating condition affecting over 20 million people in the United States alone, resulting in significant functional disability and chronic pain for patients. Unfo... Peripheral nerve injuries are a common and potentially devastating condition affecting over 20 million people in the United States alone, resulting in significant functional disability and chronic pain for patients. Unfortunately, even when repaired under optimal conditions with cutting-edge techniques, current approaches to peripheral nerve repair result in incomplete functional recovery and chronic pain in over half of patients, highlighting the pressing need for the development of new strategies for peripheral nerve repair. Biomaterials, due to their tunable properties, can be rationally designed to address many aspects of peripheral nerve repair, making them a promising solution for improving functional outcomes following nerve repair. This review discusses the current lack of efficacious treatments for peripheral nerve repair and how biomaterials can fill this crucial void, as well as what properties those materials should have from a material, biological, and practical concerns perspective. The review is divided into three main sections, the first of which outlines the complex process of peripheral nerve repair, providing an understandable and clinically germane overview of peripheral nerve repair. Part two of this review discusses biological design principles to engineer biomaterials that favor nerve regeneration. Part three discusses practical considerations for adapting biomaterials for clinical use.

Assessment of the Use of Hybrid Film With Titanium Deposition on AISI 316-L Stainless Steel Substrate as a Biomaterial.

Longhi M, Zini LP, Pereira VB … +4 more , Maurmann N, Pranke P, Santos V, Ferreira JZ

J Biomed Mater Res A · 2025 Jun · PMID 40474510 · Publisher ↗

Metals play a fundamental role in medicine, particularly in the replacement, stabilization, and reinforcement of human body structures, due to their excellent mechanical performance. However, the biocompatibility of thes... Metals play a fundamental role in medicine, particularly in the replacement, stabilization, and reinforcement of human body structures, due to their excellent mechanical performance. However, the biocompatibility of these materials is a critical factor, as they must not induce adverse reactions or pathologies when in contact with bodily fluids, which could lead to implant rejection by the host organism. Among the widely used metals, AISI 316-L stainless steel (SS) stands out for its mechanical properties and lower cost but presents limitations related to corrosion in biological environments, leading to the release of nickel and chromium ions, which are harmful to the human body. A promising alternative to mitigate these effects is the use of biocompatible coatings. In this context, the present study aimed to develop and characterize different hybrid films on AISI 316-L SS substrates for medical applications. The coatings were based on the alkoxide precursors 3-(trimethoxysilylpropyl)methacrylate (MAP) and tetraethyl orthosilicate (TEOS), applied via dip-coating and followed by titanium thin film deposition through magnetron sputtering. The results indicated good interaction between the hybrid layer, the titanium thin film, and the substrate. The HF sample, composed of only one silane-based layer, exhibited the lowest surface roughness (16.7 ± 0.6 nm Ra) compared with pure AISI SS (27.3 ± 1 nm Ra), which positively influenced the contact angle, achieving a value of (69.1° ± 0.3°), promoting cell adhesion and osseointegration-key factors for the clinical success of implants. Surfaces coated with titanium for 10 and 20 min (HF_Ti10 and HF_Ti20) on AISI 316-L SS demonstrated contact angles similar to SS (83.4° ± 0.4°), indicating a hydrophilic behavior. Additionally, no cytotoxicity was observed in the coated samples compared with the control group after 14 days in lactate dehydrogenase (LDH) assays, and HF_Ti10 presented the lowest cytotoxicity. Adherent stem cells were found in all experimental groups. These findings suggest that pre-treatment with silane-based HF, followed by titanium thin film deposition, holds great potential for application in AISI 316-L SS materials in the medical field, contributing to the development of safe and effective implants.

Cell/Surface Interactions and Osseointegration of Ti-6AI-4V: Effects of Laser Microgrooves, Hydroxyapatite Nanorods, and Arginyl-Glycyl-Aspartic Acid (RGD) on Ti-6Al-4V.

Etinosa PO, Salifu AA, Osafo SA … +3 more , Eluu SC, Obayemi JD, Soboyejo WO

J Biomed Mater Res A · 2025 Jun · PMID 40464440 · Publisher ↗

This work presents the results of an experimental study of surface-modified Ti-6Al-4V designed to enhance implant integration with human fetal osteoblast (hFOB) cells. Three surface profiles-laser-grooved (LG), Hydroxyap... This work presents the results of an experimental study of surface-modified Ti-6Al-4V designed to enhance implant integration with human fetal osteoblast (hFOB) cells. Three surface profiles-laser-grooved (LG), Hydroxyapatite (HA)-coated laser-grooved (LGH), and arginyl glycyl aspartic acid (RGD)-functionalized HA-coated laser-grooved (LGHR)-were developed and evaluated for their effects on hFOB cell attachment, spreading, proliferation, and ECM formation over a 28-day period. Cell-laden surfaces were analyzed using scanning electron and fluorescence microscopies, and cell proliferation was quantified using the Alamar Blue assay to provide additional insights. The surface characterization revealed that the LG substrate facilitated contact guidance, promoting directional cell alignment and attachment. The LGH substrate additionally created a bioactive interface by mimicking natural bone tissue, releasing calcium and phosphate ions that enhanced cell attachment and spreading. The LGHR substrate provided specific biological cues, further improving early cell attachment, accelerating proliferation, and promoting extracellular matrix (ECM) formation. Quantitative analysis confirmed that LGHR surfaces exhibited the highest cell density, areal coverage, and metabolic activity, particularly during the initial stages of culture, emphasizing the synergistic effects of HA and RGD coatings in accelerating osseointegration. This novel approach offers robust improvements in implant-tissue integration, accelerating wound healing and enhancing tissue compatibility, with promising implications for orthopedic and dental applications.

RETRACTION: Simultaneous Linear Release of Folic Acid and Doxorubicin from Ethyl Cellulose/Chitosan/g-C3N4/MoS2 Core-Shell Nanofibers and its Anticancer Properties.

J Biomed Mater Res A · 2025 Jun · PMID 40450705 · Publisher ↗

A. Nouri, B. F. Dizaji, N. Kianinejad, A. J. Rad, S. Rahimi, M. Irani, and F. S. Jazi, "Simultaneous Linear Release of Folic Acid and Doxorubicin from Ethyl Cellulose/Chitosan/g-C3N4/MoS2 Core-Shell Nanofibers and its An... A. Nouri, B. F. Dizaji, N. Kianinejad, A. J. Rad, S. Rahimi, M. Irani, and F. S. Jazi, "Simultaneous Linear Release of Folic Acid and Doxorubicin from Ethyl Cellulose/Chitosan/g-C3N4/MoS2 Core-Shell Nanofibers and its Anticancer Properties," Journal of Biomedical Materials Research Part A 109, no. 6 (2021): 903-914, https://doi.org/10.1002/jbm.a.37081. The above article, published online on 09 August 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, J. Kent Leach; and Wiley Periodicals LLC. A third party notified the publisher that they had found evidence of image manipulation in Figures 6A, 6C, and 6D. An investigation by the publisher confirmed that elements in those figures had been copied and manipulated to compose each image. The retraction has been agreed due to the evidence of image manipulation which fundamentally compromises the conclusions presented in the article. The corresponding author Mohammad Irani disagrees with this decision. The other authors did not respond.

Study on the Application of Zeolitic Imidazolate Framework-8 Loaded With Artemisia Argyi Essential Oil in the Treatment of Bacterial Infected Wounds.

Xu Y, Li Y, Ye Z … +5 more , Wang C, Cui P, Zhou S, Qiu L, Wang J

J Biomed Mater Res A · 2025 Jun · PMID 40448391 · Publisher ↗

Wound bacterial infection deteriorates with antibiotic misuse, boosting bacterial drug resistance, threatening human health. Therefore, combining natural antibacterials with efficient broad-spectrum materials offers new... Wound bacterial infection deteriorates with antibiotic misuse, boosting bacterial drug resistance, threatening human health. Therefore, combining natural antibacterials with efficient broad-spectrum materials offers new solutions. Artemisia argyi is a kind of medicinal plant distributed in Asia, known for its rich biological active compounds. With the advancement of modern analytical technology, Artemisia argyi has shown excellent antibacterial and anti-inflammatory potential, particularly Artemisia argyi essential oil (AAEO) which is considered to be the most active substance in Artemisia argyi. However, its practical application is limited due to its poor water solubility, strong volatility, high sensitivity to light and heat, and its irritating odor. Zeolitic imidazolate framework-8 (ZIF-8) is a type of metal-organic framework material (MOF) with good biocompatibility, simple synthesis, high porosity, and antimicrobial activity. ZIF-8 can be used as an ideal vehicle for the preparation of antibacterial materials. In this study, we loaded AAEO onto ZIF-8 to successfully develop AAEO@ZIF-8 antibacterial nanomaterial. The bactericidal ability and antibacterial mechanism of AAEO@ZIF-8 were evaluated through in vitro experiments such as bacterial coating, Live/Dead staining, and crystal violet staining. It was confirmed that AAEO@ZIF-8 had significant antibacterial activity against both Staphylococcus aureus and Escherichia coli. In in vivo experiments, the wound model using C57BL/6 male mice was established, and wound tissue staining with Gram, CD31 immunohistochemistry, H&E, and Masson staining was performed to evaluate the antibacterial activity of AAEO@ZIF-8. The results showed that AAEO@ZIF-8 exhibited the best wound repair performance in the model. These findings suggested that AAEO@ZIF-8 is a novel and effective antimicrobial nanomaterial targeting pathogenic bacteria. This study successfully transformed the storage mode of AAEO from liquid to solid, providing a promising strategy for the application of AAEO in the treatment of wound bacterial infections.

Understanding the Mechanical Properties of Pituitary Adenomas for Optimized Surgery.

Gautam U, Jangir H, Jain H … +4 more , Suri V, Garg A, Roy S, Suri A

J Biomed Mater Res A · 2025 Jun · PMID 40448379 · Publisher ↗

Pituitary adenoma (PA) is a common brain tumor located in a small cavity at the cranial base. It disrupts hormonal balance and compresses the optic nerves, leading to abnormal body growth, sexual dysfunction, vision loss... Pituitary adenoma (PA) is a common brain tumor located in a small cavity at the cranial base. It disrupts hormonal balance and compresses the optic nerves, leading to abnormal body growth, sexual dysfunction, vision loss, and mortality if untreated. Its surgical resection is highly challenging due to its small size, heterogeneous structure, deep location, and indistinct interface with surrounding nerves, arteries, and brain tissues. Mechanical properties of tumor tissues play a crucial role in their microstructure, growth, and progression. However, data on the mechanical properties of PA tissues is scarce. This study aims to provide detailed mechanical properties of various PA tissues and demonstrate the differences in stiffness between tumors and brain tissues. The viscoelastic properties and collagen content of postoperative PA tissues (n = 40) and normal human brain white matter (n = 7) were analyzed using in vitro nanoindentation and histological staining, respectively. Tumor consistency was also assessed preoperatively via magnetic resonance images (MRIs) and intraoperatively through surgeon feedback. PA tissues exhibited a considerable variation in viscoelastic properties; however, their average stiffness was significantly higher than normal brain white matter (p < 0.05). Tumors with firm consistency showed higher collagen content (29.8% 21.2%) than the soft (9.1% 8.1%) and medium (12.9% 9.7%) consistency tumors, however the correlation with mechanical properties was not strong (r = 0.40, p = 0.01). Strong correlations between preoperative predictions, intraoperative observations, and postoperative measurements emphasize the clinical relevance of these findings. These results underscore the potential of mechanical biomarkers to enhance surgical strategies, improve outcomes, and support applications in diagnosis, development of elastography and elastic image fusion algorithms, as well as in robot-assisted interventions.

Intelligent Sensing Switches in Drug Delivery Systems: Mechanisms, Material Selection, and Future Perspectives.

Chen F, Li H, Zhen C … +6 more , Lin G, Tang B, Shi Y, Wang L, Qiao J, Li X

J Biomed Mater Res A · 2025 Jun · PMID 40448364 · Publisher ↗

The intelligence and controllability of drug delivery systems (DDS) are crucial for enhancing therapeutic efficacy and minimizing side effects. Among these, DDS responsive switches play a pivotal role in precisely regula... The intelligence and controllability of drug delivery systems (DDS) are crucial for enhancing therapeutic efficacy and minimizing side effects. Among these, DDS responsive switches play a pivotal role in precisely regulating the timing and spatial distribution of drug release in response to specific physiological environments within the body or external stimuli. Based on the origin of stimuli, they can be categorized into endogenous and exogenous stimuli. This paper reviews various types of stimulus-responsive switches, including dual-stimulus responsive switches, and elaborates on the drug release mechanisms of each intelligent switch. It summarizes the advantages and limitations of different stimulus-responsive systems, highlights the properties of commonly used temperature-sensitive materials, and discusses the applications of popular nano-engineered materials in pH and electromagnetic-responsive switches. Finally, the paper provides an outlook on the future of DDS, focusing on achieving more precise control, as well as ensuring clinical stability and reliability.

A 3D Cell Culture Platform for Evaluating Macrophage-Liposome Conjugates in Combination Chemotherapy.

Kuo CC, Liao WY, Lin YJ … +1 more , Lee CH

J Biomed Mater Res A · 2025 Jun · PMID 40439616 · Publisher ↗

Macrophage-based drug delivery systems, such as macrophage-liposome conjugates (Mϕ-Lip), leverage the natural tumor-homing ability of macrophages and offer a potential solution for overcoming biological barriers and deli... Macrophage-based drug delivery systems, such as macrophage-liposome conjugates (Mϕ-Lip), leverage the natural tumor-homing ability of macrophages and offer a potential solution for overcoming biological barriers and delivering chemotherapy drugs to challenging tumor regions. However, reliable platforms to assess the tumor-targeting efficiency, penetration capabilities, and therapeutic effectiveness of drug-laden macrophages remain largely unavailable. In this study, we developed a three-dimensional (3D) cell culture platform that mimics the structural and biological complexity of in vivo tumors, enabling real-time observation and analysis of Mϕ-Lip as they migrate, penetrate, and exert anti-tumor effects. Beyond evaluating the delivery process, this work focuses on the rational design and optimization of dosage regimens for co-delivering cisplatin (CDDP) and paclitaxel (Taxol) using Mϕ-Lip. Experimental results demonstrated that the drugs encapsulated within the liposomes influenced the invasive behavior of Mϕ-Lip, which in turn impacted their tumor-killing efficiency. Using this 3D cell culture platform, we identified optimal dosage regimens for co-delivering combination chemotherapy drugs through the Mϕ-Lip. This newly developed approach provides a reliable and versatile tool not only for evaluating but also for fine-tuning cell-based drug delivery strategies. It holds significant promise for advancing targeted chemotherapy strategies and improving therapeutic outcomes for solid tumors.

Biomimetic Dermatopontin-Collagen Nanocomposite for Accelerated Wound Healing and ECM Remodeling in Chronic Wound Conditions.

Murali P, Solaimuthu A, Korrapati PS

J Biomed Mater Res A · 2025 Jun · PMID 40434143 · Publisher ↗

Chronic cutaneous wounds are often accompanied by an extensive alteration in the standard extracellular matrix (ECM) architecture, leading to dysfunction of the resident cells and impaired healing. Conventional wound dre... Chronic cutaneous wounds are often accompanied by an extensive alteration in the standard extracellular matrix (ECM) architecture, leading to dysfunction of the resident cells and impaired healing. Conventional wound dressings often fail to address these complex tissue repair needs associated with chronic conditions. Here, we developed a biomimetic collagen-based scaffold, collagen/chitosan/MO NPs/DPT (CCMD), involving the skin-bridge protein dermatopontin (DPT) and molybdenum trioxide (MO NPs) nanoparticle in regulating the repairing cascades in chronic conditions. The sustained release of DPT increased cellular proliferation, cellular adhesion, wound contraction, and regulation of fibronectin in fibroblast cells. Furthermore, the CCMD in influencing angiogenesis was validated by the ex vivo and in vivo assays. The results revealed that the CCMD scaffold promoted endothelial sprouting and blood capillary density, signifying its pro-angiogenic potential and role in vascular reformation, which is ideal for tissue regeneration. Thus, our findings postulate that biomimetic CCMD could serve as a better dermal substrate for ECM reorganization and present new opportunities for pathological-relevant tissue repair in chronic environments.
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