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Biomaterials Advances
Elsevier
Biomaterials Advances

Elsevier

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2772-9516

Biomaterials Advances/Journal Biomaterials Advances
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    Bone-seeking tumor cells alter bone material quality parameters on the nanoscale in mice

    Johannes KrugChristine PlumeyerAnton DavydokSofie Dragoun Kolibova...
    214060.1-214060.14页
    查看更多>>摘要：Bone metastases related to breast and prostate cancer present with multiple challenges and skeletal related events like fragility fractures impair the quality of life of the patients significantly. To determine local alterations in bone material quality with bone metastasis, we subjected murine tibial specimens, generated after intratibial injections of either RM1 prostate cancer cells or EO771 breast cancer cells into male and female mice respectively, to high-resolution imaging modalities. Small and wide-angle X-ray scattering showed unaltered mineral characteristics in the more osteosclerotic prostate cancer model, while the quantification of calcium weight percentage via backscattered electron microscopy determined minor differences along the perilacunar bone matrix. Further analyses of mineral and collagen characteristics were performed using Raman spectroscopy and focused ion beam electron microscopy. Our study indicates that alterations in nanochannel properties occur due to the presence of bone seeking tumor cells with more prevalent nanopores in the perilacunar matrix.
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    pH responsive and zwitterionic micelle for enhanced cellular uptake and antitumor performance

    Lu ZhangYue ShenTiantian ZhangXiaohua Jiang...
    214082.1-214082.14页
    查看更多>>摘要：The side effects of small molecule chemotherapeutic drugs (SMCD) have brought great pain to the cancer patients. Many nanodrug carriers can relieve the shortcomings of SMCD, but they have complex synthesis processes and lack biodegradability. To overcome both problems, we synthesized a pH responsive biodegradable zwitterionic molecules (EK-D) by linking zwitterionic polypeptide (EK7) and dodecyl acrylate through a simple click reaction. Subsequently, doxorubicin (DOX) was physically encapsulated within the EK-D micelles to produce EK-D-DOX micelles, and polyethylene glycol monooleate (POO) employed as a comparative group for the preparation of POO-DOX micelles. The results show that EK-D-DOX micelles have good aqueous stability and anti-protein non-specific adsorption performance at pH 7.4, but EK-D-DOX micelles aggregate under the condition of pH = 5.5 due to the biodegradability of EK-D. The tumor cell uptake rate of EK-D-DOX micelles is higher than that of POO-DOX micelles and free DOX, which makes EK-D-DOX micelles the highest cytotoxic. Additionally, EK-D-DOX micelles release more DOX in a slightly acidic environment than at pH 7.4, and the release of DOX reaches a significant cumulative value of 75.20 % under pH conditions of 5.5. More importantly, EK-D-DOX micelles exhibit superior in vivo tumor inhibitory efficacy compared to free DOX, resulting in a remarkable tumor inhibition rate of 95.7 %. EK-D-DOX micelles not only have lower biological toxicity to normal tissues than free DOX, but also have a longer blood circulation time in mice. The method of EK-D-DOX micelles preparation represents a new method to prepare biodegradable zwitterionic nanodrug.
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    Electricallymodified bacterial cellulose tailored with plant based green materials for infected wound healing applications

    Manjila AdhikariBianza Moise BakadiaLi WangYing Li...
    214087.1-214087.18页
    查看更多>>摘要：Effective treatment of infected wounds remains a challenge due to the rise of antibiotic-resistant microorganisms. The development of advanced materials with strong antimicrobial properties is necessary to address this issue. In this study, a unique composite of electrically modified bacterial cellulose (EBC) with allantoin (ABC) and zein was developed by dipping diffusion method. Morphological structural analysis revealed a uniform distribution of zein and aligned fibers, confirming the synthesis of the ABC-Zein composite. The formation of ABC-Zein was further confirmed by attenuated total reflection-Fourier transform infrared (ATR-FTIR), which displayed additional peaks corresponding to EBC, indicating the incorporation of zein into ABC. X-ray diffraction (XRD) analysis of ABC-Zein demonstrated a similar crystalline structure with EBC. The ABC-Zein showed mechanical integrity (tensile strength: 1.15 ± 0.21 MPa), thermal stability (degradation temperature: 290 ℃), porous structure (porosity: 40.23 ± 0.21 %), and hydrophilic (water contact angle: 53.3 ± 5.3°) properties. Furthermore, the antimicrobial agent terpinen-4-ol (T4O), derived from tea tree oil, was incorporated into the ABC-Zein composite. Biological studies confirmed the antimicrobial efficacy (Staphylococcus aureus inhibition: 88.5 ± 7.19 %) and biocompatible (cell viability: 84.95 ± 5.6 %, hemolysis: 4.479 ± 0.39 %) nature of the T4O-ABC-Zein composite. The combined effects of the aligned fiber structure, zein protein, and antimicrobial T4O significantly enhanced infected wound healing by day 7, promoting inflammatory response, granular tissue formation, cell proliferation, and angiogenesis. By day 14, T4O-ABC-Zein facilitated complete wound healing, with reepi-thelization, collagen I deposition, and downregulation of CD 31, Ki67, and a-SMA. Overall, the innovative T4O-ABC-Zein composite, with an aligned fiber structure, improved biocompatibility, and antimicrobial properties, holds significant potential for the treatment of infected wounds.
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    Functional outcome of cell seeded tracheal scaffold after mechanical stress in vitro

    R.J.J. de WitD. TiemessenE. OosterwijkA.F.T.M. Verhagen...
    214088.1-214088.8页
    查看更多>>摘要：Tracheal tissue engineering is still facing major challenges: realization of efficient vascularization and mechanical properties comparable to native trachea need to be achieved. In this study, we present a strategy for the manufacturing of a construct for tracheal tissue engineering by conditioning through cell seeding followed by mechanical stimulation in vitro. Scaffolds derived from porcine trachea decellularized with supercritical carbon dioxide were seeded with stem cells of different tissue sources and cultured in a bioreactor for 21 days under mechanical stimulation. Enhanced chondrogenic development was demonstrated, with improved sulphated glycosaminoglycan secretion and cellular alignment which resulted in mechanical properties resembling native trachea. This method may provide a useful addition to tracheal tissue engineering strategies aimed at optimizing cartilage formation.
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    Monophasic hyaluronic acid-silica hybrid hydrogels for articular cartilage applications

    Huijun ZhangJessica FaberSilvia BuddayQingsen Gao...
    214089.1-214089.12页
    查看更多>>摘要：Hyaluronic acid (HA), an FDA-approved natural polymer and important component of the extracellular matrix (ECM), has been widely used to develop hydrogels for cartilage regeneration. However, HA hydrogels often exhibit poor mechanical properties and unsuitable degradability, limiting their capability to support cell growth in cartilage. To overcome these challenges, this study modifies HA with a silica precursor and the coupling agent (3-Glycidyloxypropyl) trimethoxysilane (GPTMS) to develop a monophasic organic-inorganic hybrid HA-silica hydrogel. In this system, the inorganic silicate and organic HA components interpenetrate and bond cova-lently at the molecular level. The HA-silica hybrid hydrogel achieves a compressive modulus of 143 kPa at the highest GPTMS/HA molar ratio of 400. Additionally, in vitro cell studies show that these hybrid hydrogels have no cytotoxicity against MC3T3-E1 and ATDC-5 cells. Cell viability and morphology tests further confirm excellent cell adhesion on the hybrid scaffold. These results indicate that the developed HA-silica hybrid hydrogel is a suitable candidate for cartilage regeneration applications.
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    Development and in vitro assessment of injectable, adhesive, and self-healing chitosan-based hydrogels for treatment of spinal cord injury

    Catia CorreiaDaniela PeixotoDiana Soares da CostaRui L. Reis...
    214090.1-214090.10页
    查看更多>>摘要：Injured spinal cords have a limited ability to regenerate because of the inhibitory environment formed in situ that affects neuronal regrow. Ensuring stable contact between the injuried nerves to support neural regeneration in the lesion microenvironment remains a significant challenge. To address this challenge, we have engineered a new injectable and adhesive hydrogel to treat spinal cord injuries. This hydrogel was produced by functionalizing chitosan with catechol groups and crosslinking it with different amounts of β-glycerophosphate to obtain adhesive hydrogels with tunable mechanical properties. The softest hydrogel (G' ～300 Pa) demonstrated strong adhesion to different biological soft tissues, including porcine skin (adhesion strength of 3.4 ± 0.9 kPa) and spinal cord, as well as injectability and self-healing abilities, making it ideal for a minimally invasive administration in difficult-to-reach areas. Additionally, this composition promoted the attachment, viability, proliferation, and the expression of neuronal marker β-Ⅲ tubulin (Tuj-1) by the neuroblastoma SH-SY5Y cells. Moreover, SH-SY5Y cells cultured on the hydrogel modulated its mechanical properties (G' ～ 3500 Pa). In summary, we propose a material that is compatible with different therapies for soft tissue healing, including repairing injured nerve tissue.
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    Patterned glycopeptide-based supramolecular hydrogel promotes the alignment and contractility of iPSC-derived cardiomyocytes

    Vania I.B. CastroSara AmorimDavid CaballeroCatarina M. Abreu...
    214091.1-214091.10页
    查看更多>>摘要：The functional restoration of a damaged cardiac tissue relies on a synchronized contractile capacity of exogenous and/or endogenous cardiomyocytes, which is challenging to achieve. Here, we explored the potential of the short glycopeptide diphenylalanine glucosamine-6-sulfate (FFGlcN6S) conjugated with an aromatic moiety, namely fluorenylmethoxycarbonyl (Fmoc), to enhance cardiac tissue regeneration. At physiological conditions, Fmoc-FFGlcN6S assembles into nanofibrous hydrated meshes, i.e., matrix mimicking hydrogels. These hydrogels can be further micropatterned allowing co-existence of hierarchical structures at different lenght. The patterned hydrogels support the culture of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and promote their alignment. The cultured iPSC-CMs exhibit anisotropic synchronized contractions, indicating maturation and electrical interconnectivity. Moreover, the cultures express specific cardiac markers including, connexin-43 and sarcomeric-α-actinin, confirming enhanced cell-cell crosstalk, spontaneous contractility, and efficient transmission of electrical signals. Our results showcase the potential of short amphiphilic glycopeptides to mimic physical and biochemical cues that are essential for cardiomyocytes functionality and thus, these conjugates can be used in cardiac tissue engineering and regeneration.
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    3D printed cell-free bilayer porous scaffold based on alginate with biomimetic microenvironment for osteochondral defect repair

    Hui WangJiaxin ZhangHaotian BaiChenyu Wang...
    214092.1-214092.15页
    查看更多>>摘要：Despite significant progress in repairing osteochondral injuries using 3D printing technology, most cartilage layer scaffolds are made of degradable materials, making it difficult to simultaneously provide extracellular matrix functionality while replicating the mechanical properties of natural cartilage layers. Additionally, their degradation rate is challenging to align with cartilage regeneration. Furthermore, double-layer scaffolds commonly used for repairing osteochondral often exhibit inadequate bonding between the cartilage layer scaffolds and bone layer scaffolds. To solve these problems, we presented a bilayer scaffold composed of a 3D printed non-degradable thermoplastic polyurethane (TPU) scaffold filled with hydrogel (Gel) made of gelatin and sodium alginate as the cartilage layer (noted as TPU/Gel), meanwhile, a 3D printed polylactic acid (PLA) scaffold containing 10 % hydroxyapatite (HA) as the bone layer (noted as PLA/HA). At the junction of the bone layer and cartilage layer, TPU tightly bonded with the bone layer scaffold under high temperatures. The hydrogel filling within the TPU layer of cartilage served not only to lubricate the joint surface but also aided in creating a 3D microenvironment. The non-degradable nature of TPU allowed the cartilage layer scaffold to seamlessly integrate with the surrounding regenerated cartilage, achieving permanent replacement and providing shock absorption and weight-bearing effects. This effectively addressed the mechanical challenges associated with cartilage regeneration and resolved the inconsistency between cartilage regeneration and material degradation rates.
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    A macromolecule infliximab loaded reverse nanomicelles-based transdermal hydrogel: An innovative approach against rheumatoid arthritis

    Dildar KhanNaveed AhmedAdil MuhammadKifayat Ullah Shah...
    214093.1-214093.17页
    查看更多>>摘要：Infliximab (IFX) is used as a biotherapeutic agent for the treatment of rheumatoid arthritis (RA); however, its biological activity is lost orally because of variations in gastric pH and enzymatic degradation, and reduced bioavailability. The authors have tried to improve the efficacy of macromolecule delivery through transdermal route. Polycaprolactone-Polyethylene glycol-Polycaprolactone (PCL-PEG-PCL) triblock copolymer previously synthesized and was used as an efficient carrier for the preparation of IFX loaded reverse nanomicelles (IFX-RNMs). The RNMs were fabricated via nanoprecipitation technique, characterized and then were incorporated into a Carbopol-based hydrogel with eucalyptus oil (EO) as a penetration enhancer. The optimized RNMs had a particle size of 72.32 nm and an encapsulation efficiency of 83 %. In vitro release, exhibited a sustained pattern of IFX from the prepared carrier system, ex-vivo skin permeation and fluorescence microscopic studies revealed that IFX-RNMs loaded hydrogel with EO markedly improved permeation. An in vivo study was carried out on a CFA-induced RA mice model that revealed significant improvements in the results of behavioral parameters, biochemical assays, histopathological and radiological analysis. Overall, the results concluded that the IFX-RNMs loaded hydrogel can be used as a suitable approach for treating RA.
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    VEGF loading heparinized hyaluronic acid macroporous hydrogels for enhanced 3D endothelial cell migration and vascularization

    Daohuan LuKehan CaiZhiwen ZengJun Huang...
    214094.1-214094.9页
    查看更多>>摘要：The formation of robust vascular systems within voluminous scaffolds remains a formidable barrier in the realm of tissue engineering. There is a growing interest in the integration of biomaterial scaffolds with multiple physical and chemical stimuli to augment the process of vascularization. This study aims to investigate the combined impact of macroporous structures and vascular endothelial growth factor (VEGF) on cell migration and vascularization. Heparinized hyaluronic acid (HepHA) macroporous hydrogels with differing pore sizes, composed by methacrylated hyaluronic acid (HAMA) and methacrylated heparin (HepMA), were fabricated by a gelatin microspheres (GMS) template leaching method. After characterization of their physical properties, VEGF was immobilized on the HepHA hydrogels. The in vitro release study indicated that the HepHA hydrogels can provide sustained release of VEGF. Subsequently, cells migration of human umbilical vein endothelial (HUVECs) assessment indicated that HUVECs cultured on VEGF-loaded HepHA hydrogels with larger pores (VEGF@He-pHA250) migrated the furthest. Finally, the hydrogels were implanted and evaluated using a dorsal subcutaneous model. The histological analyses conducted in vivo were consistent with the in vitro results, VEGF@HepHA250 hydrogels exhibited the most pronounced vascularization four weeks post-implantation, indicating that hydrogels with expanded pores and an enriched VEGF promoted angiogenesis within the hydrogels. This study sheds light on the synergistic effects of VEGF release on 3D cell migration and vascularization within hydrogels of differing pore sizes, thus providing novel insights into the strategic design and fabrication of tissue-engineered scaffolds that are amenable to vascularization.
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    • Elsevier