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J Biomed Mater Res A [JOURNAL]

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Lidocaine-TiO Composite Coating for Chest Tubes: Modulating Sustained Drug Release, Antiadhesive Performance, and Antibacterial Properties.

Ding Y, Zhang Q, Xu M … +6 more , Lu Q, Kan Z, Xu Z, Feng Q, Chen A, He B

J Biomed Mater Res A · 2026 Apr · PMID 41968601 · Publisher ↗

Chest tubes used in cardiothoracic surgery must meet critical clinical requirements, including effective analgesia, inhibition of protein adhesion, and prevention of infection. In this study, a dual-layered coating was d... Chest tubes used in cardiothoracic surgery must meet critical clinical requirements, including effective analgesia, inhibition of protein adhesion, and prevention of infection. In this study, a dual-layered coating was developed, comprising an inner lidocaine (LDC) layer for localized analgesia and an outer TiO layer that serves three functions: modulating the sustained-release kinetics of LDC, providing antiadhesive properties, and offering antibacterial activity. The LDC-TiO quantum dot coating was prepared via dip-coating, which involved an initial reaction between the LDC intermediate layer and hydroxyl groups on the pretreated polyurethane surface, followed by reaction with the outer TiO. Scanning electron microscopy revealed a uniform dispersion of quantum dot-sized TiO within the LDC layer, forming a 4 μm-thick composite coating. In vitro drug release assays showed sustained LDC release over 24 h, maintaining a concentration of 0.14-0.48 mg mL from the LDC-TiO coating, meeting the requirement of clinically effective analgesic concentration. Furthermore, the catheter with LDC-TiO coating exhibited a substantial reduction in protein adhesion to 0.071 mg cm, compared with 0.343 mg cm for the single LDC coating, indicating effective antiadhesive efficacy. In addition, the antibacterial performance, evaluated via bacterial plate counting, demonstrated significant inhibition against Escherichia coli (43.72%) and Staphylococcus aureus (70.14%). The enhancements in sustained-release behavior, antiadhesive properties, and antibacterial activity are attributed to the hydrophilic and antimicrobial properties of the outer TiO coating. The proposed LDC-TiO coating is promising for achieving sustained drug release and reducing catheter-related infections.

Localized Antiadhesive Hydrogel Barriers for Prevention of Postoperative Adhesion.

Komatsu H, Watanabe S, Nagasaka K … +3 more , Ito S, Minamisakamoto S, Taguchi T

J Biomed Mater Res A · 2026 Apr · PMID 41964299 · Publisher ↗

Postoperative adhesions are frequent and serious complications that lead to longer operative times and high medical costs. Various types of antiadhesive materials, including films, solutions, and hydrogels, have been dev... Postoperative adhesions are frequent and serious complications that lead to longer operative times and high medical costs. Various types of antiadhesive materials, including films, solutions, and hydrogels, have been developed; however, they have limitations in providing localized antiadhesive properties, maintaining low volume change, and allowing for rapid preparation suitable for minimally invasive procedures. Here, we developed in situ-forming hydrogel barriers based on decanoyl group-modified Alaska pollock gelatin (C10-am-ApGltn) and a poly(ethylene glycol)-based crosslinker (4S-PEG). The resulting hydrogels adhered to the desired intestinal tissue surfaces and showed antiadhesive property within 60 s. The hydrogel barriers that adhered to the tissue were stable for at least 2 days in an aqueous environment. The hydrogel barrier prepared from 4 w/v% C10-ApGltn showed no volume changes after immersion in saline for 24 h. The gelation time of the hydrogel was within 4 s when the concentration of C10-ApGltn ranged from 4 to 15 w/v%; however, it slowed at 2 w/v%. The freeze-dried 4 w/v% C10-am-ApGltn sample rapidly dissolved in a buffer solution within a few min without heating. Furthermore, 4S-PEG for 4 w/v% C10-am-ApGltn sample dissolved within 3 s. An in vivo rat adhesion model revealed that the hydrogel barrier of 4 w/v% C10-ApGltn showed antiadhesive property, complete degradation behavior, and wound healing property within 2 weeks. With its antiadhesive effects, stable volume, and short preparation time, the hydrogel barrier developed from 4 w/v% C10-am-ApGltn has the potential to be used as a localized barrier for the prevention of postoperative adhesion.

Surface-Modified Electrospun Polyurethane Tubular Scaffold for Engineering Renal Proximal Tubule Constructs.

Sudha A, Natarajan A, Ramirez KA … +4 more , Vijayan VM, Moore R, Thomas V, Dean D

J Biomed Mater Res A · 2026 Apr · PMID 41947350 · Publisher ↗

The renal proximal tubule (PT) is central to kidney physiology and is particularly susceptible to injury; however, in vitro systems that accurately replicate its microenvironment and functional characteristics remain lim... The renal proximal tubule (PT) is central to kidney physiology and is particularly susceptible to injury; however, in vitro systems that accurately replicate its microenvironment and functional characteristics remain limited. To address this need, we report the fabrication and surface modification of electrospun polyurethane (PU) tubular scaffolds designed to enhance epithelial compatibility and support functional behavior of renal PT epithelial cells (RPTECs). While PU provides robust mechanical strength and flexibility for tubular constructs, its inherent hydrophobicity limits cell attachment; therefore, scaffolds were surface modified via tetraethoxy silane (TEOS) plasma deposition (PU-P) and Type I collagen coating (PU-C). Surface characterization demonstrated increased roughness and significantly improved hydrophilicity, as evidenced by reduced water contact angles in PU-P (97.26° ± 1.92°) and PU-C (64.1° ± 2.96°). These modifications promoted enhanced protein adsorption, with BSA and laminin binding increasing by 1.7-fold and 1.8-fold, respectively, compared with unmodified tubules. Cytocompatibility assessment confirmed high cell viability across all scaffold types (> 90%). RPTECs cultured on surface-modified electrospun PU tubules exhibited efficient adhesion, well-spread morphology, and organized cytoskeletal architecture, indicating improved cellular compatibility. In contrast, cell attachment on unmodified tubules was minimal. Immunofluorescence analysis demonstrated robust expression of renal PT markers, including Aquaporin 1 and Collagen IV, on modified scaffolds, while expression was weak or absent on unmodified constructs, indicating maintenance of the PT phenotype. Functional assessment revealed a threefold increase in alkaline phosphatase activity on coated tubules over 14 days compared with 2D culture, reflecting enhanced brush border activity and improved epithelial functional behavior. Overall, surface modification of electrospun PU tubular scaffolds significantly improves RPTEC adhesion, phenotype preservation, and functional activity, supporting the development of physiologically relevant renal PT models for in vitro applications.

Comparing Collagen and Decellularized Extracellular Matrix in Different Fabrication Contexts for Bladder Tissue Engineering.

Heidarian E, Naji M, Setareyi R … +7 more , Shirinsokhan A, Rahimpour M, Torbati PM, Ansari E, Kianirad S, Feizollahi N, Nekoonam S

J Biomed Mater Res A · 2026 Apr · PMID 41928646 · Publisher ↗

Biomaterials demonstrate significantly different properties based on their fabrication methods, which must be considered for their intended applications. This study compares collagen and decellularized extracellular matr... Biomaterials demonstrate significantly different properties based on their fabrication methods, which must be considered for their intended applications. This study compares collagen and decellularized extracellular matrix (dECM) as sponge and electrospun scaffolds for bladder tissue engineering. Collagen was extracted from rat tail tendons, while the extracellular matrix was obtained from decellularized rat bladders. Scaffold characterization included various techniques such as scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), contact angle measurements, swelling analysis, mechanical testing, and both in vitro and in vivo degradation studies. The biological evaluation incorporated cell attachment assays, viability testing using the MTT assay, quantitative reverse transcription PCR (qRT-PCR), histological analysis, and immunohistochemistry (IHC) staining to assess angiogenesis. In vitro studies showed that dECM-based scaffolds supported superior viability of bladder smooth muscle cells (SMCs) compared to collagen scaffolds. Furthermore, electrospun collagen scaffolds exhibited improved mechanical properties. qRT-PCR analysis revealed increased smooth muscle gene expression in collagen electrospun scaffolds, particularly on day 7, indicating accelerated maturation of SMCs. In vivo assessment demonstrated that dECM scaffolds facilitated enhanced angiogenesis compared to collagen scaffolds in both production forms, as indicated by IHC staining. However, dECM scaffolds had higher degradation rates than their collagen counterparts. Among all groups, collagen electrospun scaffolds exhibited the lowest degradation rate. The findings suggest that while dECM scaffolds enhance angiogenesis and initial cellular support, collagen scaffolds provide superior mechanical stability and controlled degradation kinetics. This makes them particularly suitable for bladder tissue engineering applications that require long-term structural integrity.

Evolving Transport Properties of Dynamic Hydrogels Enable Self-Tuning of Short- and Long-Term Cargo Delivery.

Sen S, Dong C, Jons CK … +6 more , Reineking W, Alakesh A, Eckman N, Song YE, Prossnitz AN, Appel EA

J Biomed Mater Res A · 2026 Apr · PMID 41924867 · Publisher ↗

Modulating Cargo Release Using Time-evolving Hydrogels. Modulating Cargo Release Using Time-evolving Hydrogels.

Effect of Nanotextured Stainless Steel Surface Features on Antibacterial Properties and Osteoblast Activity In Vitro.

Tripathi A, Champion JA

J Biomed Mater Res A · 2026 Apr · PMID 41924863 · Publisher ↗

Bacterial colonization and poor osteointegration are significant challenges for stainless steel implants. These issues often lead to implant-associated infections, localized tissue damage, and implant failure, which can... Bacterial colonization and poor osteointegration are significant challenges for stainless steel implants. These issues often lead to implant-associated infections, localized tissue damage, and implant failure, which can result in chronic inflammation, osteomyelitis, the need for revision surgery, and delayed recovery. While nanotextured surface features have shown antibacterial activity and osteoblast proliferation, the specific role of surface feature size is not yet fully understood. Herein, we utilized an electrochemical technique to fabricate nanoprotrusion-like features on stainless steel surfaces, with distinct morphology and topography by varying the etching time at a fixed potential. The results show that etching time directly influences surface morphology, roughness, feature size, and depth profile. As etching time increases, nanoprotrusions initially become more pronounced, but extended duration leads to their reduction. These variations in feature size on nanotextured stainless steel surfaces reveal that larger nanoprotrusion sizes created from intermediate etching times exhibit greatest antibacterial activity, while also best promoting osteoblast proliferation, calcium deposition, and alkaline phosphatase activity in vitro. These distinct functions from the same nanotexture feature sizes provide key insights into designing next-generation stainless steel implants.

Material Compatibility of Poly(Ether)urethane 80A With Vaporized Hydrogen Peroxide Sterilization: A Comprehensive Evaluation of Oxidative Stability and Biocompatibility.

Chaffin KA, Long EK, Hendrickx AL … +9 more , Witkowski A, Alkatout JA, Gitsov IPI, Sinha MN, Wolf MF, Jeffers H, Jolly M, Wegner N, Eppihimer M

J Biomed Mater Res A · 2026 Apr · PMID 41923704 · Publisher ↗

Poly(ether)urethanes (PEUs) are widely used in long term implanted medical devices. Their susceptibility to oxidative degradation has raised concerns regarding compatibility with vaporized hydrogen peroxide (VHO) sterili... Poly(ether)urethanes (PEUs) are widely used in long term implanted medical devices. Their susceptibility to oxidative degradation has raised concerns regarding compatibility with vaporized hydrogen peroxide (VHO) sterilization. This study investigates the chemical and mechanical stability of PEU80A, a Shore 80A durometer PEU, following exposure to VHO sterilization. Two VHO sterilization conditions were characterized, three times (nominal) and 10 times (extreme) the cycle required for cardiac pacemaker sterilization and compared to two solution-based hydrogen peroxide exposures, with and without cobalt chloride catalyst. Compared to the extreme VHO condition, the solution exposure conditions were four orders of magnitude higher in concentration and 40-fold longer in duration. Comprehensive characterization of PEU80A included molar mass analysis, antioxidant quantification, mechanical testing, free radical profiling, soft segment loss assessment, exhaustive chemical extraction, and evaluations of hemocompatibility and cytotoxicity. The results demonstrated that VHO sterilization did not induce any detectable degradation in PEU80A, even after 3 years of real-time aging post VHO exposure. Only the catalyzed solution exposure resulted in measurable oxidative degradation, evidenced by antioxidant depletion, molar mass reduction, soft segment depletion, and mechanical weakening. Despite these changes, the comprehensive testing for chemical extractables, hemocompatibility, and cytotoxicity, used to evaluate biocompatibility, remained unaffected. These findings demonstrated the continued oxidative stability and biocompatibility of PEU80A after VHO sterilization, supporting its use as a terminal sterilization method for implantable devices comprised of this material. Furthermore, these data suggest that the biostability of a material is impacted long before any changes in biocompatibility can be resolved.

Osteoblastic Responses of Sandblasted TA6V Femoral Implants Functionalized With Phosphonate Polymers via UV-Induced Direct Grafting.

Lechaptois L, Pereira C, Le Cann S … +1 more , Falentin-Daudré C

J Biomed Mater Res A · 2026 Apr · PMID 41913596 · Publisher ↗

Most of the orthopedic implants are nowadays manufactured using titanium or titanium alloy materials due to their mechanical properties and good compatibility with human tissues. Still, implant rejections frequently occu... Most of the orthopedic implants are nowadays manufactured using titanium or titanium alloy materials due to their mechanical properties and good compatibility with human tissues. Still, implant rejections frequently occur and are related to a loss of the osteointegration, which in turn is strongly linked to the implant surface's features. In particular, an increase in the roughness or functionalization with bioactive groups of the surface of a Ti implant demonstrates an enhanced osteointegration. In this study, we analyze the osteointegration of a femoral implant made of Ti alloy (TA6V) with high roughness (≈3.5 μm) and functionalized with polyvinyl benzyl phosphonic acid bioactive polymers (p(VBP)). The TA6V sample surfaces were sandblasted to increase their surface roughness and then followed a two-step UV-induced grating polymerization process to covalently link p(VBP) polymers to their surfaces. The prepared surfaces were characterized at each step using scanning electron microscopy coupled with energy dispersive spectroscopy (SEM-EDS), Fourier-transform infrared spectroscopy (FTIR), water contact angle measurement (WCA), and colorimetry (TB assay). Then, samples were incubated with MC3T3-E1 osteoblast cells, and cell viability, cell morphology, alkaline phosphatase activity, and formed calcium ions were evaluated. Finally, an in vivo study was carried out by integrating the grafted femoral implants in rabbits for 6 and 12 weeks, followed by quantitative ultrasound measurements (QUS) of the bone/implant interface. Successful grafting of p(VBP) is demonstrated on the rough TA6V surfaces, and in vitro results show an enhanced integration and activity of the osteoblastic cell.

Mechanism of Bone Marrow Mesenchymal Stem Cells-Derived Extracellular Matrix for Articular Cartilage Repair.

Sun N, Zhang Z, Li L … +3 more , Liu S, Fu B, Zeng C

J Biomed Mater Res A · 2026 Apr · PMID 41889152 · Publisher ↗

Articular cartilage injuries present a significant clinical challenge due to the tissue's limited self-repair capacity and the inadequacy of current regenerative strategies. This study aimed to investigate whether bone m... Articular cartilage injuries present a significant clinical challenge due to the tissue's limited self-repair capacity and the inadequacy of current regenerative strategies. This study aimed to investigate whether bone marrow mesenchymal stem cell-derived extracellular matrix (BM-ECM) enhances cartilage repair and to elucidate the underlying molecular mechanisms involving ubiquitin-specific protease 7 (USP7). Rat BMSCs were isolated and characterized, and decellularized BM-ECM was prepared. Cartilage defects in a rat model were treated with GelMA hydrogel scaffolds loaded with BMSCs and BM-ECM. Histological evaluation demonstrated that the BM-ECM composite scaffold significantly improved cartilage repair. Further mechanistic investigation revealed that BM-ECM promoted chondrogenic differentiation of BMSCs, an effect closely associated with USP7 activity. Overexpression of USP7 enhanced ECM synthesis and chondrogenesis, whereas USP7 knockdown diminished these processes and abolished the prochondrogenic benefits of BM-ECM. In conclusion, BM-ECM facilitates cartilage regeneration, with USP7 playing a central role in mediating its chondro-supportive effects, offering a promising therapeutic target for cartilage repair.

Anti-Biofilm Properties of Polyurethane Biomaterials Tethered With Small Molecules via Polyethylene Glycol Linker.

Liu J, Chen C, Booth JL … +5 more , Lanza M, Sun D, Allcock HR, Siedlecki CA, Xu LC

J Biomed Mater Res A · 2026 Apr · PMID 41889124 · Publisher ↗

Biofilm-associated microbial infection is one of the main complications for long-term use of biomaterials in implantable medical devices. Bacterial intracellular nucleotide second messenger signaling is widely recognized... Biofilm-associated microbial infection is one of the main complications for long-term use of biomaterials in implantable medical devices. Bacterial intracellular nucleotide second messenger signaling is widely recognized to be involved in biofilm formation and assists bacteria in monitoring and responding appropriately to changing environments. Interference with the nucleotide signaling mechanisms by small molecules to interrupt biofilm formation provides a novel way to control microbial infection on biomaterial surfaces. This study reports an approach to tether small molecule derivatives of 4-arylazo-3,5-diamino-1 H-pyrazole (termed as SP02 and SP03) on polyurethane biomaterial surfaces using a polyethylene glycol (PEG) linker. Compared to our previous approach to tether small molecules on surfaces using a short hexamethylene diisocyanate (HMDI) linker, the new modification resulted in surfaces enriched with a higher density of small molecules, SP02 and SP03. Studies of S. epidermidis and P. aeruginosa biofilm formation on surfaces demonstrated that PEG-linked surfaces were more resistant to biofilm formation than the HMDI-linked surfaces. The analysis of intracellular nucleotides in biofilm cells showed that the PEG-linked surfaces significantly reduced c-di-AMP levels in S. epidermidis cells and c-di-GMP levels in P. aeruginosa cells. In vivo experiments with a 7-day subcutaneous rat model suggest that the new small molecule tethered surfaces by the extended PEG linkers show increased resistance to microbial infection and are biocompatible to tissues. Overall, the results suggest that the PEG long linker can be used to tether small molecules on polyurethane biomaterial surfaces and retain the activity of small molecules, providing a new approach to combat microbial infections.

Cobalt-Doped Biphasic Calcium Phosphate Orchestrates Osteogenesis-Angiogenesis Signals via Hypoxia-Mimetic Signaling.

Suter LC, de Almeida GS, Dos Santos MLP … +4 more , Carra MGJ, Ferreira MR, Saeki MJ, Zambuzzi WF

J Biomed Mater Res A · 2026 Apr · PMID 41870332 · Publisher ↗

We engineered a cobalt-doped biphasic calcium phosphate (CoBCP) by combining monetite-derived pyrophosphate and β-tricalcium phosphate (β-TCP) with lattice-incorporated Co, and evaluated its physicochemical profile and i... We engineered a cobalt-doped biphasic calcium phosphate (CoBCP) by combining monetite-derived pyrophosphate and β-tricalcium phosphate (β-TCP) with lattice-incorporated Co, and evaluated its physicochemical profile and in vitro bioactivity relevant to bone regeneration. Thermoanalytical (TGA/DTA), X-ray diffraction with Rietveld refinement, and FTIR/Raman confirmed monetite-pyrophosphate conversion after calcination, phase-pure β-TCP, and an approximately equimolar Co-containing biphasic composition in CoBCP; SEM/EDX verified appropriate microstructure and cobalt incorporation. Conditioned-medium assays in MC3T3-E1 pre-osteoblasts demonstrated cytocompatibility (MTT, crystal violet) and preserved collective migration (wound healing), with CoBCP, BCP, and CoCaP 1100 matching osteogenic medium in 24-h gap closure. Gene expression revealed that CoBCP selectively coordinated early proliferation and osteogenic-angiogenic programs: CDK2 was strongly induced at 3 and 7 days (≈300-fold at day 7 vs. control), RUNX2 rose across groups with BCP/CoBCP approximating osteogenic medium at day 7, and ALP was disproportionately elevated by CoBCP (~8-fold at day 3; ~400-fold at day 7). VEGF was sensitive among ceramics, with modest induction in CoCaP and CoBCP at day 3 and pronounced upregulation in TCP and BCP at day 7, while HIF-1α was highest in CoCaP at day 7, consistent with hypoxia-mimetic signaling. Cytoskeletal/adhesion transcripts diverged over time: β-TCP/BCP upregulated Src and Cofilin at day 7, whereas CoBCP selectively increased FAK, suggesting maturing focal-adhesion signaling. Gelatin zymography detected MMP-2/-9 activity across all groups with comparable magnitudes during the early window. Collectively, CoBCP provides a cytocompatible, bioactive milieu that synchronizes proliferation, adhesion, osteogenesis, and angiogenesis, supporting its potential use in orthopedic and dental bone regeneration; future work will map cobalt dose-response and ion release, and validate efficacy and safety in direct-contact and in vivo models.

Tiger Tongue-Inspired Bionic Microneedle Patch With Dual Mechanical-Pharmacological Functions for Enhanced Wound Healing.

Niu Y, Ren J, Zhao K … +9 more , Ma T, Wang Y, Chen X, Zheng C, Chen L, Li Y, Cao X, Xu L, You X

J Biomed Mater Res A · 2026 Apr · PMID 41870317 · Publisher ↗

Effective skin wound healing requires reliable fixation and infection prevention. Inspired by the inclined papillary structure of the tiger's tongue, we developed a biomimetic microneedle patch that integrates mechanical... Effective skin wound healing requires reliable fixation and infection prevention. Inspired by the inclined papillary structure of the tiger's tongue, we developed a biomimetic microneedle patch that integrates mechanical stability with antibacterial function. The patch was fabricated via thermal pressing of polylactic acid (PLA) microneedles followed by localized drug loading at the microneedle tips. Its design includes a clamping structure, a dual-array of inclined drug-releasing PLA microneedles, a nonwoven fabric base, and a flexible adhesive layer. In vitro tests demonstrated a penetration force of 0.25 N, enhanced fixation through biomimetic interlocking, and controlled drug release for antibacterial effects. In vivo studies using a male Wistar rat model showed that the patch secured wounds, reduced inflammation, and promoted collagen deposition. These results demonstrate that this drug-loaded biomimetic microneedle patch promotes the healing of full-thickness skin wounds and exhibits superior efficacy compared to drug-free biomimetic microneedle treatments. This study advances wound care by combining biomechanical and pharmacological strategies. Future work will optimize biocompatibility and explore clinical applications.

Self-Assembling Hydrogel for Controlled Release of bFGF and Ang-1 Mimetic Peptide Promotes Neurovascular Repair in Ischemic Stroke Rats.

Nie A, Nie W, Zhou N … +4 more , Li R, Zhang R, Shi C, Yuan H

J Biomed Mater Res A · 2026 Apr · PMID 41870311 · Publisher ↗

Self-assembling peptide hydrogels represent a promising strategy for growth factor delivery and tissue repair, with the advantage of sustained release and micro-environment response characteristics. In the present study,... Self-assembling peptide hydrogels represent a promising strategy for growth factor delivery and tissue repair, with the advantage of sustained release and micro-environment response characteristics. In the present study, a multiple biofunctional self-assembling hydrogels-FGFP/TIMP-AMP was constructed, which comprised three key components: (1) a basic fibroblast growth factor-mimetic peptide (FGFP), (2) an angiopoietin-1-mimetic peptide (AMP), and (3) a microenvironment-responsive TIMP sequence designed to target MMP-2. The FGFP/TIMP-AMP could assemble into a hydrogel under physiological conditions with a suitable pore size for cell growth. In vitro, it significantly promoted HUVEC migration and tube formation. Using a PC12 deprivation of oxygen and glucose (OGD) model, it effectively reduced apoptosis and protected against hypoxia. Furthermore, the bFGF/TIMP-AMP assembling hydrogels enhanced neuronal survival, vascular regeneration, and blood-brain barrier (BBB) repair in a middle cerebral artery occlusion (MCAO) rat model. These morphological improvements further promoted the recovery of motor function in behavioral tests. Therefore, these results highlighted the therapeutic potential of FGFP/TIMP-AMP assembling hydrogel for the repair of ischemic stroke.

Safety, Distribution, and Pharmacokinetics of Biodegradable P(AAm-co-MAA) Nanogels Following Systemic Administration in Mice.

Ajeeb R, Joshi H, Ghanbari Mehrabani M … +2 more , Pierce C, Clegg JR

J Biomed Mater Res A · 2026 Apr · PMID 41870308 · Full text

Systematic analysis of the fate of hydrogel nanoparticles after in vivo administration is essential for their clinical translation. Biodegradable, disulfide-crosslinked synthetic nanogels are a promising platform for the... Systematic analysis of the fate of hydrogel nanoparticles after in vivo administration is essential for their clinical translation. Biodegradable, disulfide-crosslinked synthetic nanogels are a promising platform for the delivery of therapeutic molecules, but their biodistribution and clearance profiles remain underexplored compared to other solid nanoparticles. In this study, we investigated the safety, pharmacokinetics, tissue, and cellular distribution profiles of poly(acrylamide-co-methacrylic acid) (P(AAm-co-MAA)) nanogels following a single intravenous or intraperitoneal injection. The nanogels exhibited rapid clearance from plasma, followed by early distribution primarily to the kidneys, liver, and small intestine. Within the liver, the nanogels showed preferential uptake by endothelial cells and resident macrophages. We further revealed organ-specific differences in nanogel retention and clearance, with highly perfused organs demonstrating parallel clearance behavior with plasma, while organs such as the kidneys and small intestine served as sites of longer nanogel retention. Single injections of P(AAm-co-MAA) nanogel suspension did not induce any systemic innate immune activation nor organ-specific toxicity, demonstrating a promising safety profile. These findings provide new insights into the in vivo behavior of redox-responsive nanogels and provide a framework for their rational design and clinical translation.

Fiber-Reinforced Composites for Vaginal Tissue Engineering Applications.

Kolluru SS, Hamdaoui A, Mascot AM … +4 more , Sutcliffe SS, Lowder JL, Oyen ML, Zambuto SG

J Biomed Mater Res A · 2026 Mar · PMID 41804228 · Full text

The vagina is a fibromuscular tube-shaped organ that plays critical roles in menstruation, pregnancy, and female sexual health. Vaginal tissue constituents, including cells and extracellular matrix components, contribute... The vagina is a fibromuscular tube-shaped organ that plays critical roles in menstruation, pregnancy, and female sexual health. Vaginal tissue constituents, including cells and extracellular matrix components, contribute to tissue structure, function, and prevention of injury and pathology. However, much microstructural function remains unknown, including how the fiber-cell and cell-cell interactions influence macromechanical properties. A deeper understanding of these interactions will provide critical information needed to reduce and prevent vaginal pathologies. Our objective for this work is to design a novel tissue-mimicking biomaterial for vaginal tissue engineering, and characterize its biological and mechanical performance in the vaginal microenvironment. We successfully created fiber-reinforced hydrogels of gelatin-elastin electrospun fibers infiltrated with gelatin methacryloyl hydrogels. Further, we extensively characterized its relevant mechanical behavior, including tensile and tear properties. We also demonstrate initial biocompatibility and stability of the composites using primary vaginal epithelial cells in acidic vaginal conditions. This work significantly advances progress in vaginal tissue engineering by developing a physiologically relevant novel material with tunable properties, equipped to investigate biomechanical and cellular mechanisms underlying vaginal function, pathology, and therapeutic intervention.

Investigating the Impact of Fused Filament Fabrication Process Parameters on the Compressive Properties of Porous PEEK and PEKK Biomaterials.

Tetteh AE, Smith JA, Porter DA … +2 more , Di Prima MA, Kurtz SM

J Biomed Mater Res A · 2026 Mar · PMID 41804224 · Publisher ↗

Additive manufacturing (AM) can create orthopedic devices with integrated porosity that enables bone fixation post-implantation. While porosity is key in promoting bone ingrowth and long-term fixation, the device must pr... Additive manufacturing (AM) can create orthopedic devices with integrated porosity that enables bone fixation post-implantation. While porosity is key in promoting bone ingrowth and long-term fixation, the device must provide adequate mechanical strength and functionality. Since AM process parameters dictate the final mechanical performance of printed parts, identifying key process parameter levels that preserve or improve such behavior in load-bearing devices with integrated porosity is essential. Using a Taguchi design of experiments, gyroid-structured polyether-ether-ketone (PEEK) and polyether-ketone-ketone (PEKK) specimens were fabricated via fused filament fabrication (FFF) AM to examine the impact of nozzle temperature (T), chamber temperature (T), and layer height (LH) on their compressive mechanical behavior. In addition to compression testing, the printed specimens were analyzed using optical microscopy, scanning electron microscopy, and micro-computed tomography. Elevated processing conditions, specifically high T combined with thick LH, can enhance heat retention, slow crystallization, increase strut thickness, and improve bonding at strut junctions, enabling porous PEEK and PEKK to withstand higher compressive loads. The elastic moduli of all the porous specimens were more sensitive to variations in processing conditions than their yield strength. Notably, the more amorphous PEKK specimens achieved over 87%-88% of PEEK's calculated elastic modulus in this study and 87%-90% of the yield strength without undergoing annealing. These results are promising, considering that, like PEEK, the elastic modulus of the porous PEKK fell within the range of trabecular bone, while its yield strength surpassed that of trabecular bone.

A New Perspective in Nanocellulose-Based Materials for Biomineralization and Strategies for Bone Repair.

Barba Godinez JM, Tinajero-Díaz E, Peresin MS … +2 more , García Carvajal ZY, Gomez-Maldonado D

J Biomed Mater Res A · 2026 Mar · PMID 41795599 · Publisher ↗

Repairing large bone defects is a significant clinical challenge. In this context, cellulose nanomaterials, such as bacterial nanocellulose (BNC), cellulose nanofibrils (CNF), and cellulose nanocrystals (CNC), have emerg... Repairing large bone defects is a significant clinical challenge. In this context, cellulose nanomaterials, such as bacterial nanocellulose (BNC), cellulose nanofibrils (CNF), and cellulose nanocrystals (CNC), have emerged as promising alternatives due to their natural origin and mechanical properties. Particularly noteworthy is their chemical malleability, which thereby confers specific functionalities. This comprehensive literature review evaluates the efficacy of nanocellulose scaffolds for the repair of critical bone defects, with a focus on the impact of surface modifications. The effects of inserting bioactive functional groups and adding metal ions are analyzed in vitro and in vivo models. The parameters evaluated include material mineralization (production and precipitation of biogenic apatite, Ca/P ratio), cell adhesion and proliferation, bioadsorption, degradation, and toxicity. The results discussed provide valuable insights into the chemical and biological processes of bone formation, supporting a new paradigm: cellulose is no longer just an "eco-friendly filler" but has become a programmable structural scaffold. The trends highlighted in this review open new avenues for the treatment of bone diseases and tissue regeneration.

Matrix-Dependent Effects of Phytic Acid on Konjac Glucomannan and Hyaluronic Acid Films for Biomedical Applications.

Zasada L, Gencer I, Chmielniak D … +6 more , Brzezinska MS, Wróbel M, Dembińska K, Sobiepanek A, D'Amora U, Kaczmarek-Szczepańska B

J Biomed Mater Res A · 2026 Mar · PMID 41793054 · Publisher ↗

Chronic wounds and bacterial infections present significant challenges in tissue regeneration, demanding the development of advanced bioactive materials that balance biocompatibility, antimicrobial activity, and tunable... Chronic wounds and bacterial infections present significant challenges in tissue regeneration, demanding the development of advanced bioactive materials that balance biocompatibility, antimicrobial activity, and tunable physical properties. This study explores the multifunctional role of phytic acid (PA) when incorporated into biopolymer films based on konjac glucomannan (KG) and hyaluronic acid (HA), focusing on how the matrix composition modulates PA's effects on film properties relevant to biomedical applications. PA incorporation significantly influenced water uptake, mechanical strength, and surface characteristics in a matrix-dependent manner. In HA-based films, PA promoted matrix compaction, reduced water content, and enhanced antioxidant activity, whereas in KG-based films, PA induced an increase in water retention and less pronounced antioxidant effects. Surface energy and wettability were favorably altered by PA in both systems, supporting potential improvements in cell-material interactions. Cytocompatibility assays confirmed the nontoxic nature of the films, with KG-based formulations demonstrating higher metabolic compatibility. Notably, PA incorporation suppressed bacterial metabolic activity in Pseudomonas aeruginosa and Escherichia coli, especially in HA-based matrices, while Staphylococcus aureus remained largely unaffected. These results underscore the potential of PA as a tunable additive and natural crosslinking agent and highlight the importance of polymer selection in optimizing film functionality. Finally, this work offers valuable insights into the development of sustainable, bioactive materials suitable for tissue engineering such as wound healing.

Electrospun Silk Fibroin/Poly(Vinyl Alcohol) Nanofibrous Dressings Co-Loaded With Teicoplanin and Liposomal Curcumin: Fabrication, Physicochemical Characterization, and Antibacterial Performance.

Eghtedar FA, Movaffagh J, Molavi AM … +5 more , Gheybi F, Azari Z, Nasiri SN, Sadeghi-Avalshahr A, Nazarnezhad S

J Biomed Mater Res A · 2026 Mar · PMID 41772823 · Publisher ↗

Electrospun silk fibroin (SF)/poly(vinyl alcohol) (PVA) nanofibrous mats co-loaded with teicoplanin (Tp) and nanoliposomal curcumin (LC) were fabricated to combine extracellular matrix (ECM) mimetic architecture with dua... Electrospun silk fibroin (SF)/poly(vinyl alcohol) (PVA) nanofibrous mats co-loaded with teicoplanin (Tp) and nanoliposomal curcumin (LC) were fabricated to combine extracellular matrix (ECM) mimetic architecture with dual antimicrobial and regenerative functionality. Tp and LC were homogeneously incorporated into SF and PVA, respectively, and electrospun under optimized voltage and flow conditions to yield defect-free fibers. Morphological analysis confirmed a consistent nanofiber diameter and a water uptake of 364.17% ± 42.25%, while in vitro degradation in PBS progressed to 45.74% ± 3.99% mass loss after 28 days. Tensile testing demonstrated a breaking strength of 5.39 MPa, indicating sufficient mechanical integrity for wound application. Drug-release assays revealed a biphasic profile for Tp-an initial burst of 666.31 ± 6.85 μg/mL within the first 24 h, followed by sustained liberation over 4 weeks-whereas curcumin exhibited a steady release rate. Cytocompatibility studies on dermal fibroblasts showed 80.88% ± 1.60% viability, and hemolysis remained below 0.13% ± 0.03%, confirming hemocompatibility. In antimicrobial evaluations, the composite dressings achieved synergistic antibactericidal activity against Staphylococcus aureus and Pseudomonas aeruginosa, outperforming single-agent controls. These findings substantiate the T@S/LC@P scaffold as a versatile, infection-resistant dressing, promising accelerated wound healing and preventing microbial colonization.

Research on the Combined Effects of miRNAs and Immunomodulatory Peptides on Bone Regeneration in an Inflammatory Bone Immunological Milieu.

Fu Y, Xia X, Liu C … +5 more , Jiang S, Lai S, Xiao X, Yuan L, Mu Y

J Biomed Mater Res A · 2026 Mar · PMID 41761451 · Publisher ↗

The development of bone regenerative substitutes capable of orchestrating osteogenesis within inflammatory immune microenvironments remains a critical challenge. This study investigates the dual-functional immunomodulato... The development of bone regenerative substitutes capable of orchestrating osteogenesis within inflammatory immune microenvironments remains a critical challenge. This study investigates the dual-functional immunomodulatory peptide DP7-C as a microRNA (miRNA) co-delivery system to regulate osteogenic differentiation and macrophage polarization synchronously. Through systematic screening of DP7-C/miRNA nanocomplexes (miR-21, -26a, -29a, -34a, -124, -125a) in bone marrow mesenchymal stem cells (BMSCs) and RAW264.7 macrophages, we identified DP7-C/miR-124 as the optimal nanocomplex, demonstrating synergistic osteoimmunomodulatory effects. Results demonstrated that the DP7-C/miR-124 combination raised the expression of anti-inflammatory factors in inflammatory macrophages and decreased the expression of pro-inflammatory factors. It also stimulated the production of osteogenesis-related proteins BMP2 and Runx2 to promote BMSC osteogenesis. Mechanistic studies revealed bidirectional cellular crosstalk, where DP7-C/miR-124 enhanced IL-10-mediated anti-inflammatory macrophage polarization while reciprocally promoting BMSC differentiation through paracrine modulation. These findings establish DP7-C/miRNA nanocomplexes as next-generation osteoimmunomodulatory biomaterials that concurrently resolve inflammation and amplify bone regeneration through epigenetic-immune circuit regulation, offering a promising strategy for functionalized bone defect repair in inflammatory microenvironments.
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