J Biomed Mater Res A [JOURNAL]
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200 papers
Bioactive ZnO Decorated PVDF-Based Piezoelectric, Osteoconductive Nanofibrous Coatings for Orthopedic Implants.
Vaidya S, Joshi M, Ghosh S … +4 more , More N, Velyutham R, Babu SS, Kapusetti G
J Biomed Mater Res A · 2025 Aug · PMID 40778666 · Publisher ↗
Surface modification of titanium-based orthopedic implants has been investigated over the last decades to promote better bone-to-implant association, osseointegration, and fracture healing. Yet, post-surgical failure of...
Surface modification of titanium-based orthopedic implants has been investigated over the last decades to promote better bone-to-implant association, osseointegration, and fracture healing. Yet, post-surgical failure of coated orthopedic implants occurs due to poor adhesive strength, fatigue failure, high wear rate of coated materials, low biocompatibility, limited osseointegration, and stress-shielding effect. Therefore, there is an unmet clinical need to develop a smart coating strategy. Herein, we have created an electrospun nanofibrous coating for Ti-implants using piezoelectric Polyvinylidene fluoride (PVDF) polymer reinforced with osteoconductive nanofiller Zinc oxide (ZnO). We have found that by varying the ZnO content from 0.5 to 2.0 wt.% in the PVDF matrix, we can modulate the electrospun coating's mechanical, thermal, physicochemical stability, and piezoelectric characteristics. Our results proved that PVDF-ZnO nanofibrous coatings exhibit almost ~3-4 fold increase in the piezoelectric d coefficient as well as output voltage, compared to pure PVDF using Piezo-responsive Force Microscopy (PFM). Furthermore, electrically poled piezoelectric PVDF-ZnO nanofibers also demonstrated a significant increment (~5-fold) in collagen deposition, hydroxyapatite formation, and improved bio- and hemo-compatibility compared to unpoled nanofibers. Furthermore, through the in vitro experiments, we have confirmed that the piezoelectric PVDF-ZnO nanofibrous activates calcium-calmodulin mediated cellular pathway to induce cell adhesion, proliferation, and cell spreading in the osteoblast cells. Nonetheless, using the biomimetic mechanical bioreactor, we have investigated the piezoelectricity-mediated increased focal adhesion and enhanced F-actin production under the physiologically relevant (i.e., 1%) mechanical strain in bone cells. Moreover, the current study elucidates the piezoelectric-based smart, multifunctional coating strategies for developing an osteoconductive implant.
Antioxidant Cerium Oxide Nanoparticle Coatings Impart Immunomodulatory Effects by Suppressing Antigen-Specific Cytotoxic T Cell Activation.
Li Y, Abuid NJ, Huang PS … +1 more , Stabler CL
J Biomed Mater Res A · 2025 Aug · PMID 40755164 · Full text
Cellular entrapment within biostable hydrogels can decrease immunological rejection by blocking direct contact between the host and transplanted cells; however, these implants remain susceptible to deleterious inflammato...
Cellular entrapment within biostable hydrogels can decrease immunological rejection by blocking direct contact between the host and transplanted cells; however, these implants remain susceptible to deleterious inflammatory and immunological responses that can dampen their therapeutic effect. Reactive oxygen species (ROS) are key agents that facilitate these responses. While ROS is commonly attributed to general inflammation and cytotoxicity, it also plays an important role in the activation of adaptive immune cells, as ROS-mediated pathways facilitate the efficient generation of effector T cells. Herein, we explored if incorporating a potent antioxidant, specifically cerium oxide nanoparticles (CONP), onto the surface of a hydrogel-based microbead platform could deliver an immunomodulatory biomaterial capable of dampening antigen-specific effector T cell generation. To test this hypothesis, CONP-based coatings were applied to the surface of cell-containing alginate microbeads and co-cultured with immune cells. Quantification of the immune responses found that CONP-coatings decreased the generation of antigen-specific effector CD8 T cells. Interrogation of T cell and antigen-presenting cell (APC) responses found suppression was likely driven by the modulation of CD8 T cells, as APCs were only modestly impacted. Results provide insight into the capacity of CONP to deliver an immunomodulatory effect. These findings also highlight the general potential of antioxidant biomaterials to serve a dual role in protecting cells from ROS-mediated damage and suppressing adaptive immune cell responses.
Macrophage Based on Multifunctional Ta@Sr Alleviates Osteoarthritis by Modulating Chondrogenesis and Macrophage Polarization.
Liu H, Yang K, Yang Z … +3 more , Lu X, Wu J, Cui Y
J Biomed Mater Res A · 2025 Aug · PMID 40755158 · Publisher ↗
Osteoarthritis (OA) is a progressive joint disease that involves damage to the cartilage, inflammation in the synovium, and injury to the subchondral bone, which highlights the need for the creation of novel treatment op...
Osteoarthritis (OA) is a progressive joint disease that involves damage to the cartilage, inflammation in the synovium, and injury to the subchondral bone, which highlights the need for the creation of novel treatment options. Nevertheless, finding an effective method that combines anti-inflammatory properties with the ability to regenerate cartilage remains a significant challenge. TA@Sr is a bioactive coordination complex formed through chelation between tannic acid (TA) and strontium ions (Sr), exhibiting a hierarchically structured metal-phenolic network. This research presents an innovative strategy utilizing a Macrophage developed from multifunctional TA@Sr, which promotes chondrogenesis and exhibits strong anti-inflammatory effects. The Macrophage based on TA@Sr is constructed by self-assembling a single-cell layer using varying concentrations of TA and Sr on RAW264.7 cell surfaces. This Macrophage demonstrates robust biological activity, enhancing chondrocyte proliferation, differentiation, and migration, alongside the upregulation of anabolic genes such as aggrecan (ACAN) and collagen II, while simultaneously inhibiting the expression of catabolic genes like MMP13 in a dose-dependent manner under LPS-induced inflammation. In addition, TA@Sr reduces the expression of proinflammatory cytokines (TNF-α and IL-6) in macrophages and promotes their polarization to the anti-inflammatory M2 phenotype. These results suggest that TA@Sr has significant promise for treating OA by regulating both chondrogenesis and macrophage polarization simultaneously.
Polypropylene Surgical Mesh Implants for Hernia and Pelvic Floor Disorders: A Materials Performance Perspective.
Jain T, Isayeva IS, Simon DD
J Biomed Mater Res A · 2025 Aug · PMID 40717396 · Publisher ↗
Surgical meshes are medical devices that were initially designed for hernia repair and later adopted for pelvic floor reconstructive surgeries, including pelvic organ prolapse (POP) and stress urinary incontinence (SUI)....
Surgical meshes are medical devices that were initially designed for hernia repair and later adopted for pelvic floor reconstructive surgeries, including pelvic organ prolapse (POP) and stress urinary incontinence (SUI). Polypropylene (PP) is the most common material for surgical mesh, but others have been used clinically. Complications with PP surgical mesh have been attributed to several factors, including the post-implantation degradation of the surgical mesh materials. PP mesh was initially considered to be inert, but evidence of in vivo degradation has since been widely reported in retrieved surgical mesh after long-term implantation. This review provides an overview of the physical and mechanical properties of surgical mesh prior to implantation and the post-implantation stability of the mesh materials. We underscore the need to consider the changes in mesh properties after implantation and their potential effects on device safety. This review highlights the importance of characterizing "effective porosity," assessing mechanical properties under physiological stresses, understanding the in vivo degradation mechanisms, employing accelerated bench-top aging methods to estimate long-term biostability, and developing in vitro in vivo correlations (IVIVC) to minimize resource-intensive long-term testing and improve patient access to innovative devices. Overall, this review provides a materials science perspective on the research gaps that could be considered in future iterations of surgical mesh devices to improve their safety and performance.
In Vitro Assessment of a Paclitaxel-Poly(Caprolactone) Drug Delivery System in Endometrial Cancer.
Rowlands CE, Dwyer M, Givens BE
J Biomed Mater Res A · 2025 Aug · PMID 40717381 · Publisher ↗
Drug delivery systems (DDSs) have grown in popularity for their astute ability to encapsulate a drug into a biocompatible carrier, thus improving targeted and localized delivery to specific tissues. DDSs often increase c...
Drug delivery systems (DDSs) have grown in popularity for their astute ability to encapsulate a drug into a biocompatible carrier, thus improving targeted and localized delivery to specific tissues. DDSs often increase circulation time and therapeutic effects while also decreasing systemic side effects. In diseases that are difficult to treat with conventional therapies, such as endometrial cancer, DDSs are a promising therapeutic alternative. In this study, a polycaprolactone (PCL) particle loaded with the chemotherapeutic paclitaxel (PTX) was generated as a DDS and investigated for efficacy in the Ishikawa and KLE endometrial cancer cell lines. Dye-loaded particles were used to quantify particle uptake and identify cellular localization. Results indicated that polymeric encapsulation of PTX was achieved and approximately 22% of the cargo was released in the first 48 h, followed by at least 28 days of sustained release. These particles enhanced antiproliferative activity in cells at lower PTX concentrations compared with the free drug. Using a dye-loaded particle, confocal microscopy confirmed intracellular localization of the dye, particularly in the nucleus and cytoplasm, which was also quantified using fluorescence. These data indicate that PCL is a potential polymer for further development of DDS for cancer therapeutics.
Influence of Diol Chain Length on Various Properties of Citric Acid Polyesters/PLA Electrospun Nonwovens for Tissue Engineering Applications.
Bandzerewicz A, Chlanda A, Gołofit T … +3 more , Slouf M, Denis P, Gadomska-Gajadhur A
J Biomed Mater Res A · 2025 Aug · PMID 40698901 · Publisher ↗
Despite the great potential of citrate polyesters in regenerative medicine, the data about their application in electrospinning is somewhat limited. In this work, poly(dimethylene citrate) (P-1,2-ECit), poly(tetramethyle...
Despite the great potential of citrate polyesters in regenerative medicine, the data about their application in electrospinning is somewhat limited. In this work, poly(dimethylene citrate) (P-1,2-ECit), poly(tetramethylene citrate) (P-1,4-BCit), and poly(hexamethylene citrate) (P-1,6-HCit) were synthesized. Nonwovens from poly(diol citrates)/PLA mixtures were successfully electrospun and characterized using SEM, AFM, water contact angle measurement, DSC, TGA, and in vitro degradation tests. The addition of poly(diol citrates) increases the hydrophilicity and surface adhesion force of PLA nonwovens; however, the observed effects depend on the scale level (macro/micro) of the analysis. Diol chain length in poly(diol citrate) influences the compatibility and heterogeneity of its distribution within the carrier polymer. Additionally, it impacts the crystallinity of the PLA phase. Degradation tests show the problem of the nonwoven stability in the aqueous media and the high leachability of the short-chained poly(diol citrates). Addressing this issue is important regarding controlling the degradation kinetics. Despite the good processability in electrospinning and promising surface properties of the poly(diol citrates)/PLA mixtures, the instability of these materials in an aqueous environment is an important issue which can subsequently affect the performance of the eventual implant/cell scaffold. The solution may involve chain elongation of the hydrophilic oligomeric additive.
Chondroprotective Effects of Chitosan-Coated Poly(Lactic-co-Glycolic Acid) Nanocapsulized Curcumin on Human Articular Chondrocytes.
Cheng YH, Wu CC, Chen YH … +4 more , Huang PF, Hsu CW, Kato K, Yang KC
J Biomed Mater Res A · 2025 Aug · PMID 40686021 · Publisher ↗
Dysregulation of pro-inflammatory cytokines participates in the initiation and development of knee osteoarthritis (OA). Consequently, interventions to boost the anti-inflammatory capacity of articular chondrocytes have b...
Dysregulation of pro-inflammatory cytokines participates in the initiation and development of knee osteoarthritis (OA). Consequently, interventions to boost the anti-inflammatory capacity of articular chondrocytes have been proposed to treat early-stage OA and prevent OA progression. Applying nanoencapsulation can enhance bioavailability and bioactivity and sustain the anti-inflammatory activity of phytochemicals. Accordingly, in this study, we used nanocapsules to deliver curcumin (Cur) to treat inflammatory chondrocytes. Using double-emulsion technology, Cur was encapsulated in chitosan-coated poly(lactic-co-glycolic acid) nanocapsules. The nanocapsulized Cur (NCcur) was characterized, and the toxicity to human articular chondrocytes was evaluated. NCcur was applied to interleukin-1 beta (IL-1β)-stimulated cells based on findings of the Cur toxicity study. Results showed that the particle size of NCcur was 247.8 ± 1.73 nm with a zeta potential of 20.3 ± 0.11 mV and a mid-range distribution. NCcur showed a core-shell and sphere-like morphology. The encapsulation efficiency of Cur in nanocapsules was 67.1%. Nanoencapsulation decreased the toxicity of high-dose Cur (> 20 μM), and NCcur exhibited a sustained Cur release over 72 h. NCcur supplementation (20 μM) improved cell survival and ameliorated cell senescence of inflammatory chondrocytes. The IL-1β-induced IL1B, IL6, metalloproteinase-9 (MMP9), and MMP13 mRNA expressions were down-regulated, while IL10 level was enhanced in NCcur-treated chondrocytes. Likewise, NCcur supplementation restored aggrecan, collagen type II alpha 1 chain, and SOX9 mRNA expressions. MMP-13, IL-8, and MCP-1 secretions in the supernatant also decreased. By applying nanocapsules, we assumed the anti-inflammatory capacity of Cur could be sustained for treating knee OA.
Brillouin Spectroscopy: A Non-Invasive Method for Assessing the Viscoelastic Properties of Biologically Relevant Polymers.
Cheburkanov V, Jung S, Kizilov M … +4 more , Holt SE, Alge DL, Ware TH, Yakovlev VV
J Biomed Mater Res A · 2025 Jul · PMID 40653450 · Full text
Research of biocompatible polymers is critical for advancing biomedical technologies, particularly in the fields of tissue engineering, drug delivery, and cardiovascular health. This study investigates the mechanical pro...
Research of biocompatible polymers is critical for advancing biomedical technologies, particularly in the fields of tissue engineering, drug delivery, and cardiovascular health. This study investigates the mechanical properties of a series of novel biocompatible polymers using Brillouin microspectroscopy. We demonstrate the ability of Brillouin spectroscopy to accurately measure mechanical properties of these polymers on a microscopic level, which are vital for their application and can be finely tuned to match the requirements. Our findings suggest that Brillouin microspectroscopy, coupled with Raman spectroscopy, offers a powerful complementary approach to traditional viscoelasticity measurement techniques, paving the way for enhanced characterization and utilization of biocompatible polymers in medical research and clinical practice. This in turn would help streamline production and control of these polymers in a non-invasive and label-free way.
Successful Preparation of Contrast Particle-Loaded Human Mesenchymal Stem Cell Aggregates Using Adherent Cell Self-Aggregation Technique.
Teng L, Fukushima S, Koizumi M … +4 more , Okano HJ, Ohki T, Matsuura K, Iwai R
J Biomed Mater Res A · 2025 Jul · PMID 40643099 · Publisher ↗
Several studies have investigated the location of transplanted cells and tissue-engineered cell constructs in the body by incorporating contrast nanoparticles into cells by endocytosis; however, these have yet to be appl...
Several studies have investigated the location of transplanted cells and tissue-engineered cell constructs in the body by incorporating contrast nanoparticles into cells by endocytosis; however, these have yet to be applied clinically because of the complexity of assessing the safety of nanoparticles. In this study, we proposed that our developed adherent cell self-aggregation technique (CAT) could be used to develop cell aggregates loaded with contrast particles of a size that would exclude the possibility of endocytosis, and aimed to prepare these aggregates followed by biological and computed tomography (CT) contrast evaluation under X-rays. Once human bone marrow-derived mesenchymal stem cells (HBMSCs) were seeded into culture dishes coated with CAT-inducing polymer to form gapless cell monolayer sheets, tungsten carbide (WC) particles smaller than 1 μm or titanium (Ti) particles larger than 10 μm were added, and thus each particle deposited on the surface of the cell monolayer sheet. During the subsequent overnight incubation, spontaneous detachment and aggregation of the cell monolayer sheets with deposited WC and Ti particles occurred, forming single spherical cell aggregates (spheroids) and loading these particles. Histological analysis confirmed that Ti particles with a diameter of at least 10 μm were not endocytosed and remained attached to the outside of cells forming spheroids, while WC particles were endocytosed into the cells. The CT images of the Ti-loaded spheroids were clearly visible along the spheroid shape under X-ray irradiation. Then, we confirmed that there was no toxicity to the cells forming the spheroids by loading Ti particles, and the cells could sprout and proliferate by culturing the spheroids. We successfully prepared Ti particle-loaded HBMSCs aggregates with long fiber shape (> 10 cm) by applying CAT to a culture dish with a ring-fiber-shaped culture groove and confirmed their clear visibility on CT images under X-ray irradiation, as well as their containment and ejection into a catheter, demonstrating their applicability to catheter-mediated regenerative therapy.
Enhancing Bone Regeneration: The Role of Biomimetic Silicified Collagen Scaffold in Osteogenesis and Angiogenesis.
Liu MY, Ma YX, Chen L … +4 more , Wang M, Zhang ZL, Hou YX, Niu LN
J Biomed Mater Res A · 2025 Jul · PMID 40635198 · Publisher ↗
The identification of materials that effectively promote mineralization and vascularization is crucial for advancing clinical applications in bone regeneration. Biomimetic silicified collagen scaffold (SCS) has emerged a...
The identification of materials that effectively promote mineralization and vascularization is crucial for advancing clinical applications in bone regeneration. Biomimetic silicified collagen scaffold (SCS) has emerged as a promising candidate, demonstrating significant potential to enhance both osteogenesis and angiogenesis. However, the mechanisms by which SCS directly influences angiogenesis to facilitate bone defect healing remain largely unexplored. In this study, we observed that the implantation of SCS in rabbit femoral defects resulted in extensive bone regeneration and angiogenesis at the wound sites. Notably, SCS outperformed commercial alternatives such as Bio-Oss in terms of degradation and angiogenic response. In vitro assays further demonstrated that SCS upregulates angiogenic protein expression and promotes endothelial cell angiogenesis through the activation of the HIF-1α/VEGF signaling pathway. Consequently, SCS modulates the phenotype of vascular endothelial cells, leading to the formation of CD31Emcn type H endothelial cells, which are critical for effective bone regeneration. This study offers valuable perspectives on the dual effects of silicified materials on osteogenesis and angiogenesis, advancing the understanding of their potential functions in regenerative medicine.
Exponentially Decreasing Antigen Release Reduces Inflammatory Markers in an Antigen-Specific Manner.
Esrafili A, Talitckii A, Kupfer J … +7 more , Thumsi A, Jaggarapu MMCS, Dugoni M, Jensen G, Peet MM, Holloway JL, Acharya AP
J Biomed Mater Res A · 2025 Jul · PMID 40631591 · Full text
Vaccine development requires innovative approaches to improve immune responses while reducing the number of immunizations. In this study, we explore the impact of controlled antigen release on immune activation and regul...
Vaccine development requires innovative approaches to improve immune responses while reducing the number of immunizations. In this study, we explore the impact of controlled antigen release on immune activation and regulation using programmable infusion pumps and biodegradable biomaterials in OT-II and wild-type mice to understand the adaptive immune response through controlled antigen delivery in the absence of adjuvant. Ovalbumin (OVA) was delivered via an exponentially decreasing profile, mimicking clearance of infection, and an exponentially increasing profile, mimicking induction of infection. Exponentially decreasing OVA delivery through infusion pumps promoted regulatory T-cell (Treg) activation in secondary lymphoid organs and suppressed pro-inflammatory T-helper type 17 (Th17) responses in blood. An exponentially increasing OVA profile enhanced central memory T-cell (TCM) populations in submandibular blood and humoral immune responses in cardiac blood serum, demonstrating distinct immune modulation based on release kinetics. OVA was also delivered using a biodegradable PLGA-PEG-PLGA (PPP) depot, which provided controlled OVA release in an exponentially decreasing pattern. PPP-OVA treatment significantly reduced the frequency of pro-inflammatory T-helper type 1 (Th1) cells while increasing CD25FOXP3 Treg cells in the spleen. Moreover, to identify T-cell populations that most accurately characterize the divergence in Treg and T-helper response to OVA kinetics, a Sequential Feature Selection (SFS) algorithm with Machine Learning (ML) models was used. ML algorithms identified gMFI of RORγt as a key feature in submandibular blood and the ratio of gMFI of FOXP3 to GATA3 as the marker that was significantly changed by treatments in inguinal lymph nodes (iLN) when infusion pumps were used to deliver OVA. In addition, ML-based SFS identified CD25FOXP3 regulatory T cells as the most important feature, influencing the expression of other cell types in both inguinal lymph nodes (iLN) and spleen when PPP was used to deliver OVA. This finding suggests that the exponentially decreasing profile may generate anti-inflammatory responses. Overall, these findings suggest that controlled antigen delivery enhances immune regulation and memory T cells, providing new insights into immune responses mediated by the release kinetics.
Biodegradable, Antibacterial TCP Implant Coatings With Magnesium Phosphate-Based Supraparticles.
Lanzino MC, Höppel A, Le LRV … +9 more , Morelli S, Killinger A, Rheinheimer W, Mayr HO, Dembski S, Al-Ahmad A, Mayr MF, Gbureck U, Seidenstuecker M
J Biomed Mater Res A · 2025 Jul · PMID 40625240 · Publisher ↗
This work highlights the potential of porous, bioactive coatings to advance implant technology and address critical clinical challenges. A key issue in implant coatings is to achieve the balance between infection prevent...
This work highlights the potential of porous, bioactive coatings to advance implant technology and address critical clinical challenges. A key issue in implant coatings is to achieve the balance between infection prevention and successful osseointegration. Although titanium implants are widely used due to their mechanical strength and biocompatibility, their bioinert nature limits integration with bone tissue. To address these issues, porous calcium phosphate (CaP) coatings have been developed to enhance cell attachment and bone growth. However, CaP, especially in the widely used form of hydroxyapatite (HAp), has a low resorption rate, which often leads to prolonged coating stability and impairs natural bone remodeling. To overcome this limitation, magnesium phosphate (MgP), an underexplored but promising biomaterial with high biocompatibility and osteogenic potential, can be introduced. Another innovative strategy is the doping of biomaterials with antibacterial ions, among which copper (Cu) has attracted particular attention. The incorporation of Cu into the coating matrix can significantly reduce the risk of post-operative infection while promoting angiogenesis, a key factor for rapid and stable implant integration. This study presents bone implant coatings composed of tricalcium phosphate (TCP) and Cu-doped MgP clustered nanoparticles (supraparticles) fabricated via high-velocity suspension flame spraying (HVSFS). This particle system addresses current challenges in bone tissue regeneration by synergistically combining the high biodegradability of MgP, the bone-mimicking properties of CaP, and the antibacterial capabilities of Cu. In addition, the HVSFS process enables the creation of thin layers with porous microstructures. Biocompatibility of the prepared coatings was assessed using MG63 osteosarcoma cells, while the antibacterial efficacy was tested against Staphylococcus aureus and Escherichia coli. The incorporation of Cu-doped MgP supraparticles (MgPCu and MgPCu HT) into TCP coatings resulted in high Cu release and pronounced antibacterial efficacy compared to the TCP reference, while the addition of Cu-doped FT supraparticles (FTCu) led to high cell proliferation.
A Design of Experiment to Evaluate the Printability for Bioprinting by Using Deep Learning Image Similarity.
Balters L, Reichl S
J Biomed Mater Res A · 2025 Jul · PMID 40616386 · Publisher ↗
Bioprinting is a growing area in the field of tissue engineering that offers a potential solution to the global shortage of organ transplants. Ensuring high printability is crucial for bioprinting. To better understand p...
Bioprinting is a growing area in the field of tissue engineering that offers a potential solution to the global shortage of organ transplants. Ensuring high printability is crucial for bioprinting. To better understand printability, a design of experiment model that examines printing speed and pressure in extrusion-based printing was developed. Two biomaterials, hyaluronic acid and sodium alginate, were selected as surrogate biomaterials to understand how rheological properties play a role in printability. Various rheological aspects such as shear-thinning behavior, viscosity, and recovery were investigated. To further evaluate printability, a new method was used that includes deep learning image similarity. The information obtained with the surrogate bioinks was then applied to another biomaterial, methacrylated hyaluronic acid, in combination with corneal keratocytes to demonstrate the successful implementation of the outcome of this design of experiment. As a result of this study, a better understanding of the rheological properties for bioprinting was achieved, leading to a next step towards improving extrusion-based bioprinting, which can be used for a wide range of applications.
Development and Evaluation of an Innovative S-Flurbiprofen-Diethylamine Emulgel With Superior Transdermal Delivery and Analgesic Activity.
Zhang J, Han J, Zhu A … +9 more , Zhu X, Zeng Y, Yin M, Xiao Y, Wang C, Yin C, Wang X, Zhang G, Hao C
J Biomed Mater Res A · 2025 Jul · PMID 40616212 · Publisher ↗
This study aimed to develop an innovative (S-flurbiprofen)-diethylamine (SFP-DEA) emulgel formulation via incorporating SFP as the active pharmaceutical ingredient within a carbomer 940 gel matrix. SFP-DEA emulgel was sy...
This study aimed to develop an innovative (S-flurbiprofen)-diethylamine (SFP-DEA) emulgel formulation via incorporating SFP as the active pharmaceutical ingredient within a carbomer 940 gel matrix. SFP-DEA emulgel was synthesized by dissolving SFP-DEA in the aqueous phase of an oil-in-water (O/W) emulsion, followed by dispersion into a carbomer 940 gel matrix. The physicochemical stability of SFP-DEA emulgel was evaluated via centrifuge, temperature swing test, high temperature, and long-term storage at ambient conditions. Ex vivo SFP transdermal delivery of SFP-DEA emulgel was evaluated using a Franz diffusion cell combined with excised rat skin. The in vivo analgesic activity and skin irritation test of SFP-DEA emulgel were evaluated using a mouse knee osteoarthritis model and healthy rats, respectively. Results demonstrated that SFP-DEA emulgel showed robust physicochemical stability and retain a final SFP content of 1.5% (w/w). Ex vivo transdermal study demonstrated that EMG5 (the emulgel optimized with laurocapram and menthol as penetration enhancers) achieved an 8-h cumulative SFP transdermal flux of 741.28 μg/cm (44.23% of the administered dose), which is 27.94-fold higher than that of Loqoa (SFP tapes). In addition, SFP-DEA emulgel demonstrated rapid analgesic efficacy, with an 84.36% pain inhibition rate within 30 min in the osteoarthritis model, and elicited no signs of skin irritation in rats. In conclusion, the SFP-DEA emulgel developed herein exhibits high stability, enhanced transdermal delivery, preliminary analgesic activity, and favorable safety profiles, positioning it as a promising topical therapeutic candidate.
Effects of Additive Manufacturing and Sterilization on Poly(p-Dioxanone) for Short-Term Application in the Intestinal Environment.
Ficht S, Schübel L, Rojas-González DM … +8 more , Solheid JDS, Leonhardt S, Kleybolte M, Boudot C, Eblenkamp M, Steger J, Wilhelm D, Mela P
J Biomed Mater Res A · 2025 Jul · PMID 40616210 · Publisher ↗
Additive manufacturing of patient specific implants made of biodegradable polymers is receiving increasing attention in the medical sector, including the trend towards manufacturing at the point-of-care. Despite this, th...
Additive manufacturing of patient specific implants made of biodegradable polymers is receiving increasing attention in the medical sector, including the trend towards manufacturing at the point-of-care. Despite this, the changes of the polymer structure and their effects on mechanical properties and degradation behavior caused by the additive manufacturing process and subsequent sterilization are still insufficiently investigated, although of key relevance for the implant's functionality. In this study, poly(p-dioxanone) (PPDO) was processed by fused filament fabrication (FFF). The effects of manufacturing as well as two different low-temperature sterilization techniques, namely HO plasma and gamma irradiation, on the polymer structure were evaluated. Additionally, PPDO degradation was investigated by immersing the processed samples in Sorensen's phosphate buffer (PB) with pH = 6.47 for 28 days to mimic implantation in intestinal milieu and evaluated at regular time intervals. Results showed that we were able to successfully print PPDO without influencing the polymer structure or cytocompatibility. No significant changes were detected for plasma-sterilized samples (PS) while gamma-sterilized (GS) ones significantly decreased molecular weight (M and M) and showed significant lower inherent viscosity (IV) compared with the (non-sterilized) control group after processing. During immersion in PB, a decrease in M, M, and mechanical strength occurred for all samples. However, GS samples were affected to a much higher extent compared with the other groups both in final values and timeline. A degradation plateau was seen for the tensile strength of NS and PS samples over the first 21 and 17 days, respectively, followed by a steady decrease. In contrast, for the GS samples, a drastic decrease in tensile strength occurred already during the first 14 days. There was no notable mass loss detected within the first 28 days of degradation for any of the sample groups. Based on these results, we conclude that FFF with subsequent plasma sterilization is a reliable process for manufacturing PPDO devices for short-term applications that require stable mechanical conditions within the first weeks of implantation to guarantee the time needed for tissue healing before degrading, as for example, in the case of intestinal compression anastomoses. Such requirement could not be met with gamma sterilization with the dose used, because of the too fast decrease in mechanical properties.
Strontium-Loaded Titanium and Systemic Teriparatide Synergistically Enhance Osteogenesis and Osseointegration in an Osteoporotic Rabbit Model.
Shima K, Shimizu T, Yamaguchi S … +6 more , Otsuki B, Kawai T, Okuzu Y, Takaoka Y, Ikeda N, Matsuda S
J Biomed Mater Res A · 2025 Jul · PMID 40611602 · Publisher ↗
Poor osseointegration of Titanium (Ti) implants in osteoporotic bone can lead to early construct failure in clinical settings. This study investigated whether combining Strontium (Sr) surface loading (modified alkali and...
Poor osseointegration of Titanium (Ti) implants in osteoporotic bone can lead to early construct failure in clinical settings. This study investigated whether combining Strontium (Sr) surface loading (modified alkali and heat treatment) with systemic teriparatide administration could enhance implant osseointegration in osteoporotic conditions. Mouse osteoblast-like cells (MC3T3-E1) were cultured on Sr-loaded Ti surfaces with and without teriparatide administration to evaluate cell adhesion, proliferation, differentiation, and mineralization capacity. This in vivo study utilized an osteoporotic rabbit femur through ovariectomy and steroid administration. The combined treatment (Sr-loaded Ti and teriparatide) enhanced osteoblast differentiation and mineralization in vitro, with an increase in alkaline phosphatase activity and alizarin red staining. Six and twelve weeks after in vivo implantation, the combination therapy demonstrated superior outcomes compared to the single treatments (Sr-loaded Ti or teriparatide), including enhanced bone-implant interfacial strength, improved bone morphology parameters, higher mineral apposition rates, and greater bone-implant contact. These findings demonstrate that the synergistic approach of Sr-loaded Ti implants combined with systemic teriparatide administration considerably improves implant osseointegration in osteoporotic bone, suggesting a promising strategy for enhancing implant outcomes in patients with osteoporotic bone quality.
Biological Responses and Hemocompatibility of Diamond-Like Carbon Thin Films on Different PEO Interlayers for Potential Cardiovascular Stent Applications.
Shahin N, Shamanian M, Kharaziha M
J Biomed Mater Res A · 2025 Jul · PMID 40605697 · Publisher ↗
Plasma electrolytic oxidation (PEO) considerably affects controlling the degradation rate of magnesium-based implants to approach the healing period. However, the biological properties still require further improvement,...
Plasma electrolytic oxidation (PEO) considerably affects controlling the degradation rate of magnesium-based implants to approach the healing period. However, the biological properties still require further improvement, particularly for blood-contact applications, such as cardiovascular stents. This research aims to study in vitro biological properties of the duplex diamond-like carbon (DLC)/plasma electrolytic oxidation (PEO) coatings as a function of various PEO middle layers for potential cardiovascular stent applications. To this aim, two different PEO coatings including silicate and phosphate compounds were applied on AZ31 substrate as middle-layers, and a top DLC layer with 1 μm thickness was successfully synthesized on them. Moreover, the role of different PEO interlayers on the degradation behavior, biocompatibility, hemocompatibility, and its mechanism are studied. Results showed a considerable decrease in degradation rate after applying the PEO process and the PEO-Ph revealed the optimized degradation performance in just PEO-coated samples. On the other side, the best degradation performance between duplex-coated samples was obtained for DLC/PEO-Si according to its higher diamond-like structure. Moreover, the viability of human umbilical vein endothelial cells on DLC/PEO-Ph was higher than that of the DLC/PEO-Si, which might be attributed to higher protein adsorption on its surface. In the case of hemocompatibility, a considerable decrease in hemolysis ratio along with remarkable improvement in clotting behavior was observed by applying the PEO process. However, the hemolysis ratio was reduced as being safe for blood-contact applications just for duplex-coated samples. In conclusion, a promising coating for blood-contact applications based on DLC/PEO in particular in the case of DLC/PEO-Si has been provided in this study.
Iridium-Bismuth-Oxide Coatings for Use in Neural Stimulating Electrodes: The Influence of Ir/Bi Ratio.
Xu X, Ali I, Minotti S … +2 more , Durham HD, Omanovic S
J Biomed Mater Res A · 2025 Jul · PMID 40579750 · Publisher ↗
Implantable neural prosthetics with stimulating electrodes are increasingly employed in medical practices to treat neural disabilities. The electrode material is expected to provide high charge storage and injection capa...
Implantable neural prosthetics with stimulating electrodes are increasingly employed in medical practices to treat neural disabilities. The electrode material is expected to provide high charge storage and injection capacity (CSC/CIC) and low impedance for safe, efficient, and precise neural stimulation, while at the same time, being small. To improve the current state-of-the-art neural-electrode material, iridium oxide (IrOx), IrBiOx coatings of various compositions (m = 0, 0.2, 0.4, 0.6, 0.8, and 1.0) produced by thermal deposition were evaluated. The IrBiOx yielded a CSC of 17.7 ± 1.1 mC/cm, which is four-fold higher than that of IrOx. At the same time, the impedance of IrBiOx at 1 kHz was measured to be half of that of IrOx. The superior performance of IrBiOx was explained by forming amorphous structures that facilitate the intercalation of H and OH ions into deeper oxide structures that contribute to faradaic charge storage. The IrBiOx electrode also showed good stability and biocompatibility, which makes it potentially a good candidate for neural stimulating electrodes.
Multidimensional Applications and Challenges of Metal-Organic Frameworks (MOFs) in Biomedicine: From Drug Safety Evaluation to Drug Delivery.
Liu Z, Gao Y, Shao W … +4 more , Guo X, Zhao D, Yang R, Li S
J Biomed Mater Res A · 2025 Jul · PMID 40575961 · Publisher ↗
Metal-organic frameworks (MOFs) are porous materials composed of metal ions or clusters and organic ligands connected through coordination bonds, exhibiting high specific surface areas, tunable pore structures, and excel...
Metal-organic frameworks (MOFs) are porous materials composed of metal ions or clusters and organic ligands connected through coordination bonds, exhibiting high specific surface areas, tunable pore structures, and excellent chemical stability. These unique features have enabled MOFs to be widely applied in catalysis, gas separation, and environmental purification. In recent years, the potential of MOFs in the biomedicine field has garnered significant attention. MOFs offer efficient drug loading and controlled release capabilities, particularly for targeted therapies in oncology and other diseases. Furthermore, their structural versatility positions them as promising candidates for antitumor and antibacterial treatments. However, challenges related to biocompatibility, in vivo degradation, and potential toxicity need further investigation. This review explores the latest advancements in MOF applications in biomedicine, focusing on drug delivery, targeted therapy, and modification strategies, as well as toxicity assessment and mechanisms. Finally, future research directions are proposed, including the development of intelligent drug delivery systems, multimodal diagnostic platforms, and optimized MOF designs for clinical translation.
Synthesis of Chondroitin Sulfate Conjugated Nanofiber Shish Kebabs as a Biomimetic Bone Template.
Yu T, DeSantis P, Kim S … +2 more , Li CY, Marcolongo M
J Biomed Mater Res A · 2025 Jul · PMID 40566847 · Publisher ↗
Synthetic polymeric bone grafts have emerged as a promising strategy for bone tissue engineering. Polycaprolactone (PCL) nanofiber shish kebab (NFSK) templates were fabricated as synthetic bone scaffolds via polymer crys...
Synthetic polymeric bone grafts have emerged as a promising strategy for bone tissue engineering. Polycaprolactone (PCL) nanofiber shish kebab (NFSK) templates were fabricated as synthetic bone scaffolds via polymer crystallization of a block copolymer (BCP) of PCL-b-polyacrylic acid (PAA). The BCP-functionalized NSFKs provide a unique template that allows for the spatial and orientational control of the nanosized mineral crystals in the PAA anionic galleries, mimicking the molecular structure of bone. The objective of this study was to use this platform to design biomimetic bone templates by modifying the surface with biomimetic functional groups. As a result, chondroitin sulfate (CS) was conjugated onto the kebabs via 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) crosslinking of the CS terminal amine group and the PAA carboxylic acid group. Fourier-transform infrared spectroscopy (FTIR) and mass balance showed the formation of an amide bond and an increase in mass after conjugation. MC3T3 E1 pre-osteoblast cells were cultured on the CS-NFSK templates and showed that the presence of CS promoted alkaline phosphatase (ALP) activity and cell proliferation. Osteogenic gene expression, including RUNX2, ALP, COL1, and BGLAP, were upregulated in the CS-NFSK templates. For the first time, CS-NFSK was molecularly engineered to mimic the bone structure and matrix, showing promise as a biomimetic bone template.
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