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On page 1 showing 1 ~ 20 papers out of 896 papers

The effect of applied voltages on the structure, apatite-inducing ability and antibacterial ability of micro arc oxidation coating formed on titanium surface.

  • Qing Du‎ et al.
  • Bioactive materials‎
  • 2018‎

The micro arc oxidation (MAO) coatings with different concentrations of Ca, P and Zn elements are successfully formed on the titanium substrate at the different applied voltages. After MAO treatment, the MAO coating exhibits the porous surface structure and composed of anatase and rutile TiO2 phases. Meanwhile, the average size and density of micro-pores on the MAO coatings have been modified via the adjusting the applied voltages. In addition, the contents of the incorporated elements such as Zn, Ca and P elements in the MAO coatings have been optimized. The bonding strength test results reveal that the MAO coating shows higher bonding strength, which is up to 45 ± 5 MPa. Compared to the pure Ti plate, the MAO coating formed at 350 and 400 V show good apatite-inducing ability. Meanwhile, the MAO coating containing Zn, Ca and P elements have better antibacterial ability for E.coli and S.aureus. Thus, the incorporation of Zn, Ca and P elements was an effective method to improve the antibacterial ability. Moreover, the concentrations of Zn, Ca and P elements could be adjusted with the changing of the applied voltages. As a result, the enhancement of the antibacterial ability on the MAO coating surfaces was depended on the comprehensive effect of the incorporated elements and the surface property of MAO coatings.


Viable cryopreserved umbilical tissue (vCUT) reduces post-operative adhesions in a rabbit abdominal adhesion model.

  • Sandeep Dhall‎ et al.
  • Bioactive materials‎
  • 2019‎

Post-operative adhesions, a common complication of surgery, cause pain, impair organ functionality, and often require additional surgical interventions. Control of inflammation, protection of injured tissue, and rapid tissue repair are critical for adhesion prevention. Adhesion barriers are biomaterials used to prevent adhesions by physical separation of opposing injured tissues. Current adhesion barriers have poor anti-inflammatory and tissue regenerative properties. Umbilical cord tissue (UT), a part of the placenta, is inherently soft, conforming, biocompatible, and biodegradable, with antimicrobial, anti-inflammatory, and antifibrotic properties, making it an attractive alternative to currently available adhesion barriers. While use of fresh tissue is preferable, availability and short storage time limit its clinical use. A viable cryopreserved UT (vCUT) "point of care" allograft has recently become available. vCUT retains the extracellular matrix, growth factors, and native viable cells with the added advantage of a long shelf life at -80 °C. In this study, vCUT's anti-adhesion property was evaluated in a rabbit abdominal adhesion model. The cecum was abraded on two opposing sides, and vCUT was sutured to the abdominal wall on the treatment side; whereas the contralateral side of the abdomen served as an internal untreated control. Gross and histological evaluation was performed at 7, 28, and 67 days post-surgery. No adhesions were detectable on the vCUT treated side at all time points. Histological scores for adhesion, inflammation, and fibrosis were lower on the vCUT treated side as compared to the control side. In conclusion, the data supports the use of vCUT as an adhesion barrier in surgical procedures.


Modification of titanium surface via Ag-, Sr- and Si-containing micro-arc calcium phosphate coating.

  • Mariya B Sedelnikova‎ et al.
  • Bioactive materials‎
  • 2019‎

The current research is devoted to the study of the modification of the titanium implants by the micro-arc oxidation with bioactive calcium phosphate coatings containing Ag or Sr and Si elements. The coatings' microstructure, phase composition, morphology, physicochemical and biological properties were examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). Ag-containing and Sr-Si-incorporated coatings were formed in alkaline and acid electrolytes, respectively. The formation of the coatings occurred at different ranges of the applied voltages, which led to the significant difference in the coatings properties. The trace elements Ag, Sr and Si participated intensively in the plasma-chemical reactions of the micro-arc coatings formation. Ag-containing coatings demonstrated strong antibacterial effect against Staphylococcus aureus AТСС 6538-P. MTT in vitro test with 3T3-L1 fibroblasts showed no cytotoxicity appearance on Sr-Si-incorporated coatings.


Multifunctional zinc ion doped sol - gel derived mesoporous bioactive glass nanoparticles for biomedical applications.

  • Zuzana Neščáková‎ et al.
  • Bioactive materials‎
  • 2019‎

Mesoporous bioactive glasses have been widely investigated for applications in bone tissue regeneration and, more recently, in soft tissue repair and wound healing. In this study we produced mesoporous bioactive glass nanoparticles (MBGNs) based on the SiO2-CaO system. With the intention of adding subsidiary biological function, MBGNs were doped with Zn2+ ions. Zn-MBGNs with 8 mol% ZnO content were synthesized via microemulsion assisted sol-gel method. The synthesized particles were homogeneous in shape and size. They exhibited spherical shape, good dispersity, and a size of 130 ± 10 nm. The addition of zinc precursors did not affect the morphology of particles, while their specific surface area increased in comparison to MBGNs. The presence of Zn2+ ions inhibited the formation of hydroxycarbonate apatite (HCAp) on the particles after immersion in simulated body fluid (SBF). No formation of HCAp crystals on the surface of Zn-MBGNs could be observed after 14 days of immersion. Interestingly, powders containing relatively high amount of zinc released Zn2+ ions in low concentration (0.6-1.2 mg L-1) but in a sustained manner. This releasing feature enables Zn-MBGNs to avoid potentially toxic levels of Zn2+ ions, indeed Zn-MBGNs were seen to improve the differentiation of osteoblast-like cells (MG-63). Additionally, Zn-MBGNs showed higher ability to adsorb proteins in comparison to MBGNs, which could indicate a favourable later attachment of cells. Due to their advantageous morphological and physiochemical properties, Zn-MBGNs show great potential as bioactive fillers or drug delivery systems in a variety of applications including bone regeneration and wound healing.


ROS-responsive capsules engineered from EGCG-Zinc networks improve therapeutic angiogenesis in mouse limb ischemia.

  • Zuoguan Chen‎ et al.
  • Bioactive materials‎
  • 2021‎

The successful treatment of limb ischemia requires that promote angiogenesis along with microenvironment improvement. Zinc ions have been reported to stimulate angiogenesis, but application was limited to the toxicity concerns. We hypothesized that zinc based metal-EGCG capsule (EGCG/Zn Ps) can achieve sustained release Zn2+ resulting in reduced toxicity and improve angiogenesis as well as the improvement of microenvironment by ROS scavenging of EGCG. The surface morphology, zeta potential, infrared absorbance peaks and zinc ion release profile of the EGCG/Zn Ps were measured. In vitro, EGCG/Zn showed significantly antioxidant, anti-inflammatory and induced cell migration effect. In addition, EGCG/Zn Ps enabled the sustained release of zinc ions, which reduced cytotoxicity and enhanced the secretion of vascular endothelial growth factor (VEGF) in vitro and in vivo. In mouse models of limb ischemia, EGCG/Zn Ps promoted angiogenesis and cell proliferation in ischemic tissues. Moreover, EGCG/Zn Ps group exhibited the most significant recovery of limb ischemic score, limb temperature and blood flow than other groups. In conclusion, EGCG/Zn Ps is a safe and promising approach to combine the merit of Zn2+ and EGCG, thus enabling the direct application to limb ischemia.


Regulation of the inflammatory cycle by a controllable release hydrogel for eliminating postoperative inflammation after discectomy.

  • Yu Liu‎ et al.
  • Bioactive materials‎
  • 2021‎

Surgery is the final choice for most patients with intervertebral disc degeneration (IDD). Operation-caused trauma will cause inflammation in the intervertebral disc. Serious inflammation will cause tissue defects and induce tissue degeneration, IDD recurrence and the occurrence of other diseases. Therefore, we proposed a scheme to treat recurrence after discectomy by inhibiting inflammation with an aspirin (ASP)-loaded hydrogel to restore the mechanical stability of the spine and relieve local inflammation. ASP-liposomes (ASP-Lips) were incorporated into a photocrosslinkable gelatin-methacryloyl (GelMA) via mixing. This material can effectively alleviate inflammation by inhibiting the release of high mobility group box 1 (HMGB1) from the nucleus to the cytoplasm. We further assessed the expression of inflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), and degeneration-related factors, such as type II collagen (COL-2), Aggrecan, matrix metallopeptidases-3 (MMP-3), MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and ADAMTS-5 in rat nucleus pulpous cells. The level of IDD was analyzed through H&E, safranin-O staining and immunohistochemistry in rabbit samples. In vitro, we found that ASP-Lip@GelMA treatment significantly decreased inflammatory cytokines, MMP-3 and -13, and ADAMTS-4 and -5 and up-regulated COL-2 and Aggrecan via the inhibited release of HMGB-1 from the nucleus. In vivo, ASP-Lip@GelMA can effectively inhibit inflammation of local tissue after disc surgery and fill local tissue defects. This composite hydrogel system is a promising way to treat the recurrence of IDD after surgery without persistent complications.


Insight into vitronectin structural evolution on material surface chemistries: The mediation for cell adhesion.

  • Tianjie Li‎ et al.
  • Bioactive materials‎
  • 2020‎

Biomaterial surface chemistry engenders profound consequences on cell adhesion and the ultimate tissue response by adsorbing proteins from extracellular matrix, where vitronectin (Vn) is involved as one of the crucial mediator proteins. Deciphering the adsorption behaviors of Vn in molecular scale provides a useful account of how to design biomaterial surfaces. But the details of structural dynamics and consequential biological effect remain elusive. Herein, both experimental and computational approaches were applied to delineate the conformational and orientational evolution of Vn during adsorption onto self-assembled monolayers (SAMs) terminating with -COOH, -NH2, -CH3 and -OH. To unravel the interplay between cell binding and the charge and wettability of material surface, somatomedin-B (SMB) domain of Vn holding the RGD cell-binding motif was employed in molecular dynamics (MD) simulations, with orientation initialized by Monte Carlo (MC) method. Experimental evidences including protein adsorption, cell adhesion and integrin gene expressions were thoroughly investigated. The adsorption of Vn on different surface chemistries showed very complex profiles. Cell adhesion was enabled on all Vn-adsorbed surfaces but with distinct mechanisms mostly determined by conformational change induced reorientation. Higher amount of Vn was observed on negatively charged surface (COOH) and hydrophobic surface (CH3). However, advantageous orientations defined by RGD loop conditions were only obtained on the charged surfaces (COOH and NH2). Specifically, COOH surface straightened up the Vn molecules and accumulated them into a higher density, whereas CH3 surface squashed Vn and stacked them into higher density multilayer by tracking adsorption but with the RGD loops restrained. These findings may have a broad implication on the understanding of Vn functionality and would help develop new strategies for designing advanced biomaterials.


Effect of size and crystalline phase of TiO2 nanotubes on cell behaviors: A high throughput study using gradient TiO2 nanotubes.

  • Yanran Li‎ et al.
  • Bioactive materials‎
  • 2020‎

The research of TiO2 nanotubes (TNTs) in the field of biomedicine has been increasingly active. However, given the diversity of the nanoscale dimension and controversial reports, our understanding of the structure-property relationships of TNTs is not yet complete. In this paper, gradient TNTs with a wide diameter range of 20-350 nm were achieved by bipolar electrochemistry and utilized for a thorough high-throughput study of the effect of nanotube dimension and crystalline phase on protein adsorption and cell behaviors. Results indicated that protein adsorption escalated with nanotube dimension whereas cell proliferation and differentiation are preferred on small diameter (<70 nm) nanotubes. Large diameter anatase nanotubes had higher adsorption of serum proteins than as-prepared ones. But only as-prepared small diameter nanotubes presented slightly higher cell proliferation than corresponding annealed nanotubes whereas there was no discernible difference between as-prepared and annealed nanotubes on cell differentiation for the entire gradient. Those findings replenish previous research about how cell responses to TNTs with a wide diameter range and provide scientific guidance for the optimal design of biomedical materials.


Synergistic effects of immunoregulation and osteoinduction of ds-block elements on titanium surface.

  • Lan Chen‎ et al.
  • Bioactive materials‎
  • 2021‎

Ds-block elements have been gaining increasing attention in the field of biomaterials modification, owing to their excellent biological properties, such as antibiosis, osteogenesis, etc. However, their function mechanisms are not well understood and conflicting conclusions were drawn by previous studies on this issue, which are mainly resulted from the inconsistent experimental conditions. In this work, three most widely used ds-block elements, copper, zinc, and silver were introduced on titanium substrate by plasma immersion ion implantation method to investigate the rule of ds-block elements in the immune responses. Results showed that the implanted samples could decrease the inflammatory responses compared with Ti sample. The trend of anti-inflammatory effects of macrophages on samples was in correlation with cellular ROS levels, which was induced by the implanted biomaterials and positively correlated with the number of valence electrons of ds-block elements. The co-culture experiments of macrophages and bone marrow mesenchymal stem cells showed that these two kinds of cells could enhance the anti-inflammation and osteogenesis of samples by the paracrine manner of PGE2. In general, in their steady states on titanium substrate (Cu2+, Zn2+, Ag), the ds-block elements with more valence electrons exhibit better anti-inflammatory and osteogenic effects. Moreover, molecular biology experiments indicate that the PGE2-related signaling pathway may contribute to the desired immunoregulation and osteoinduction capability of ds-block elements. These findings suggest a correlation between the number of valence electrons of ds-block elements and the relevant biological responses, which provides new insight into the selection of implanted ions and surface design of biomaterials.


Additive-lathe 3D bioprinting of bilayered nerve conduits incorporated with supportive cells.

  • Jingyi Liu‎ et al.
  • Bioactive materials‎
  • 2021‎

Nerve conduits have been identified as one of the most promising treatments for peripheral nerve injuries, yet it remains unsolved how to develop ideal nerve conduits with both appropriate biological and mechanical properties. Existing nerve conduits must make trade-offs between mechanical strength and biocompatibility. Here, we propose a multi-nozzle additive-lathe 3D bioprinting technology to fabricate a bilayered nerve conduit. The materials for printing consisted of gelatin methacrylate (GelMA)-based inner layer, which was cellularized with bone marrow mesenchymal stem cells (BMSCs) and GelMA/poly(ethylene glycol) diacrylate (PEGDA)-based outer layer. The high viability and extensive morphological spreading of BMSCs encapsulated in the inner layer was achieved by adjusting the degree of methacryloyl substitution and the concentration of GelMA. Strong mechanical performance of the outer layer was obtained by the addition of PEGDA. The performance of the bilayered nerve conduits was assessed using in vitro culture of PC12 cells. The cell density of PC12 cells attached to cellularized bilayered nerve conduits was more than 4 times of that on acellular bilayered nerve conduits. The proliferation rate of PC12 cells attached to cellularized bilayered nerve conduits was over 9 times higher than that on acellular bilayered nerve conduits. These results demonstrate the additive-lathe 3D bioprinting of BMSCs embedded bilayered nerve conduits holds great potential in facilitating peripheral nerve repair.


Sericin microparticles enveloped with metal-organic networks as a pulmonary targeting delivery system for intra-tracheally treating metastatic lung cancer.

  • Jia Liu‎ et al.
  • Bioactive materials‎
  • 2021‎

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer. However, systemic chemotherapy is limited by poor therapeutic efficiency and severe toxic side effects, due to the extremely low delivery efficacy and non-specificity of anticancer drugs. Herein, we report a sericin microparticles enveloped with metal-organic networks as a pulmonary delivery system for treating lung metastasis of breast cancer in an animal model. The sericin microparticles (SMPs) were prepared using water in oil (w/o) emulsification method. After doxorubicin (DOX) loading, tannic acid (TA)/ferric irons (Fe3+) based metal organic networks (MON) were coated on the particles to obtain DOX-loaded microparticles (DOX@SMPs-MON). The SMPs-MON with good biocompatibility could effectively encapsulate DOX and sustainably unload cargos in a pH-dependent manner. The DOX-loaded microparticles could be uptaken by 4T1 cells, and effectively kill the cancer cells. In vivo, DOX@SMPs-MON was deposited in the lungs and remained for over 5 days after pulmonary administration. In contrast to conventional DOX treatment that did not show significantly inhibitory effects on lung metastatic tumor, DOX@SMPs-MON markedly decreased the number and size of metastatic nodules in lungs, and the lung weight and appearance were similar to those of healthy mice. In summary, the sericin microparticles with MON wrapping might be a promising pulmonary delivery system for treating lung metastatic cancer.


Cellulose fibers-reinforced self-expanding porous composite with multiple hemostatic efficacy and shape adaptability for uncontrollable massive hemorrhage treatment.

  • Yansen Wang‎ et al.
  • Bioactive materials‎
  • 2021‎

Uncontrollable hemorrhage leads to high mortality and thus effective bleeding control becomes increasingly important in the military field and civilian trauma arena. However, current hemostats not only present limitation when treating major bleeding, but also have various side effects. Here we report a self-expanding porous composites (CMCP) based on novel carboxymethyl cellulose (CMC) fibers and acetalized polyvinyl alcohol (PVA) for lethal hemorrhage control. The CMC fibers with uniform fibrous structure, high liquid absorption and procoagulant ability, are evenly interspersed inside the composite matrix. The obtained composites possess unique fiber-porous network, excellent absorption capacity, fast liquid-triggered self-expanding ability and robust fatigue resistance, and their physicochemical performance can be fine-tuned through varying the CMC content. In vitro tests show that the porous composite exhibits strong blood clotting ability, high adhesion to blood cells and protein, and the ability to activate platelet and the coagulation system. In vivo hemostatic evaluation further confirms that the CMCP presents high hemostatic efficacy and multiple hemostatic effects in swine femoral artery major hemorrhage model. Additionally, the CMCP will not fall off from the injury site, and is also easy to surgically remove from the wound cavity after the hemostasis. Importantly, results of CT tomography and 3D reconstruction indicate that CMCP can achieve shape adaptation to the surrounding tissues and the wound cavities with different depths and shapes, to accelerate hemostasis while protecting wound tissue and preventing infection.


Fast photocurable thiol-ene elastomers with tunable biodegradability, mechanical and surface properties enhance myoblast differentiation and contractile function.

  • Mohamed Alaa Mohamed‎ et al.
  • Bioactive materials‎
  • 2021‎

Biodegradable elastomers are important emerging biomaterials for biomedical applications, particularly in the area of soft-tissue engineering in which scaffolds need to match the physicochemical properties of native tissues. Here, we report novel fast photocurable elastomers with readily tunable mechanical properties, surface wettability, and degradability. These elastomers are prepared by a 5-min UV-irradiation of thiol-ene reaction systems of glycerol tripentenoate (GTP; a triene) or the combination of GTP and 4-pentenyl 4-pentenoate (PP; a diene) with a carefully chosen series of di- or tri-thiols. In the subsequent application study, these elastomers were found to be capable of overcoming delamination of myotubes, a technical bottleneck limiting the in vitro growth of mature functional myofibers. The glycerol-based elastomers supported the proliferation of mouse and human myoblasts, as well as myogenic differentiation into contractile myotubes. More notably, while beating mouse myotubes detached from conventional tissue culture plates, they remain adherent on the elastomer surface. The results suggest that these elastomers as novel biomaterials may provide a promising platform for engineering functional soft tissues with potential applications in regenerative medicine or pharmacological testing.


Analysis of structural components of decellularized scaffolds in renal fibrosis.

  • Rui Zhang‎ et al.
  • Bioactive materials‎
  • 2021‎

Chronic kidney disease has been recognized as a major public health problem worldwide and renal fibrosis is a common pathological process occurring in chronic renal failure. It is very promising to find the strategies to slow or even prevent the progression of fibrosis. This study focused on whether renal fibrosis decellularized scaffolds has the potential to be a model of cellular mechanisms of tissue fibrosis or donors for tissue engineering. In order to evaluate the feasibility of decellularized scaffolds derived from pathological kidneys, histology, proteomics and ELISA will be used to analysis the changes in the structure and main components of fibrotic tissue. The fibrosis model in this paper was induced by adenine-fed and the results showed that the structure of fibrotic scaffold was changed and some protein were up-regulated or down-regulated, but the cytokines associated with renal regeneration after injury were remained. In cell experiments, endothelial progenitor cells proliferated well, which proved that the fibrotic scaffolds have non-cytotoxic. All these conclusions indicate that the renal fibrosis decellularized scaffolds model has the ability to study fibrosis mechanism and the potential to be engineering donors as well as normal scaffolds.


Hierarchical macro-microporous WPU-ECM scaffolds combined with Microfracture Promote in Situ Articular Cartilage Regeneration in Rabbits.

  • Mingxue Chen‎ et al.
  • Bioactive materials‎
  • 2021‎

Tissue engineering provides a promising avenue for treating cartilage defects. However, great challenges remain in the development of structurally and functionally optimized scaffolds for cartilage repair and regeneration. In this study, decellularized cartilage extracellular matrix (ECM) and waterborne polyurethane (WPU) were employed to construct WPU and WPU-ECM scaffolds by water-based 3D printing using low-temperature deposition manufacturing (LDM) system, which combines rapid deposition manufacturing with phase separation techniques. The scaffolds successfully achieved hierarchical macro-microporous structures. After adding ECM, WPU scaffolds were markedly optimized in terms of porosity, hydrophilia and bioactive components. Moreover, the optimized WPU-ECM scaffolds were found to be more suitable for cell distribution, adhesion, and proliferation than the WPU scaffolds. Most importantly, the WPU-ECM scaffold could facilitate the production of glycosaminoglycan (GAG) and collagen and the upregulation of cartilage-specific genes. These results indicated that the WPU-ECM scaffold with hierarchical macro-microporous structures could recreate a favorable microenvironment for cell adhesion, proliferation, differentiation, and ECM production. In vivo studies further revealed that the hierarchical macro-microporous WPU-ECM scaffold combined with the microfracture procedure successfully regenerated hyaline cartilage in a rabbit model. Six months after implantation, the repaired cartilage showed a similar histological structure and mechanical performance to that of normal cartilage. In conclusion, the hierarchical macro-microporous WPU-ECM scaffold may be a promising candidate for cartilage tissue engineering applications in the future.


From waste of marine culture to natural patch in cardiac tissue engineering.

  • Yutong He‎ et al.
  • Bioactive materials‎
  • 2021‎

Sea squirt, as a highly invasive species and main biofouling source in marine aquaculture, has seriously threatened the biodiversity and aquaculture economy. On the other hand, a conductive biomaterial with excellent biocompatibility, and appropriate mechanical property from renewable resources is urgently required for tissue engineering patches. To meet these targets, we presented a novel and robust strategy for sustainable development aiming at the marine pollution via recycling and upgrading the waste biomass-sea squirts and serving as a renewable resource for functional bio-scaffold patch in tissue engineering. We firstly demonstrated that the tunic cellulose derived natural self-conductive scaffolds successfully served as functional cardiac patches, which significantly promote the maturation and spontaneous contraction of cardiomyocytes both in vitro and enhance cardiac function of MI rats in vivo. We believe this novel, feasible and "Trash to Treasure" strategy to gain cardiac patches via recycling the waste biomass must be promising and beneficial for marine environmental bio-pollution issue and sustainable development considering the large-scale consumption potential for tissue engineering and other applications.


Design of a biofluid-absorbing bioactive sandwich-structured Zn-Si bioceramic composite wound dressing for hair follicle regeneration and skin burn wound healing.

  • Zhaowenbin Zhang‎ et al.
  • Bioactive materials‎
  • 2021‎

The deep burn skin injures usually severely damage the dermis with the loss of hair follicle loss, which are difficult to regenerate. Furthermore, severe burns often accompanied with large amount of wound exudates making the wound moist, easily infected, and difficult to heal. Therefore, it is of great clinical significance to develop wound dressings to remove wound exudates and promote hair follicle regeneration. In this study, a sandwich-structured wound dressing (SWD) with Janus membrane property was fabricated by hot compression molding using hydrophilic zinc silicate bioceramics (Hardystonite, ZnCS) and hydrophobic polylactic acid (PLA). This unique organic/inorganic Janus membrane structure revealed excellent exudate absorption property and effectively created a dry wound environment. Meanwhile, the incorporation of ZnCS bioceramic particles endowed the dressing with the bioactivity to promote hair follicle regeneration and wound healing through the release of Zn2+ and SiO3 2- ions, and this bioactivity of the wound dressing is mainly attributed to the synergistic effect of Zn2+ and SiO3 2- to promote the recruitment, viability, and differentiation of hair follicle cells. Our study demonstrates that the utilization of the Janus membrane and synergistic effect of different type bioactive ions are effective approaches for the design of wound dressings for burn wound healing.


Procyanidins-crosslinked small intestine submucosa: A bladder patch promotes smooth muscle regeneration and bladder function restoration in a rabbit model.

  • Xiu-Zhen Zhang‎ et al.
  • Bioactive materials‎
  • 2021‎

Currently the standard surgical treatment for bladder defects is augmentation cystoplasty with autologous tissues, which has many side effects. Biomaterials such as small intestine submucosa (SIS) can provide an alternative scaffold for the repair as bladder patches. Previous studies have shown that SIS could enhance the capacity and compliance of the bladder, but its application is hindered by issues like limited smooth muscle regeneration and stone formation since the fast degradation and poor mechanical properties of the SIS. Procyanidins (PC), a natural bio-crosslinking agent, has shown anti-calcification, anti-inflammatory and anti-oxidation properties. More importantly, PC and SIS can crosslink through hydrogen bonds, which may endow the material with enhanced mechanical property and stabilized functionalities. In this study, various concentrations of PC-crosslinked SIS (PC-SIS) were prepared to repair the full-thickness bladder defects, with an aim to reduce complications and enhance bladder functions. In vitro assays showed that the crosslinking has conferred the biomaterial with superior mechanical property and anti-calcification property, ability to promote smooth muscle cell adhesion and upregulate functional genes expression. Using a rabbit model with bladder defects, we demonstrated that the PC-SIS scaffold can rapidly promote in situ tissue regrowth and regeneration, in particular smooth muscle remodeling and improvement of urinary functions. The PC-SIS scaffold has therefore provided a promising material for the reconstruction of a functional bladder.


Simultaneous incorporation of PTH(1-34) and nano-hydroxyapatite into Chitosan/Alginate Hydrogels for efficient bone regeneration.

  • Zhiyuan Zou‎ et al.
  • Bioactive materials‎
  • 2021‎

Tissue regeneration based on the utilization of artificial soft materials is considered a promising treatment for bone-related diseases. Here, we report cranial bone regeneration promoted by hydrogels that contain parathyroid hormone (PTH) peptide PTH(1-34) and nano-hydroxyapatite (nHAP). A combination of the positively charged natural polymer chitosan (CS) and negatively charged sodium alginate led to the formation of hydrogels with porous structures, as shown by scanning electron microscopy. Rheological characterizations revealed that the mechanical properties of the hydrogels were almost maintained upon the addition of nHAP and PTH(1-34). In vitro experiments showed that the hydrogel containing nHAP and PTH(1-34) exhibited strong biocompatibility and facilitated osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) via the Notch signaling pathway, as shown by the upregulated expression of osteogenic-related proteins. We found that increasing the content of PTH(1-34) in the hydrogels resulted in enhanced osteogenic differentiation of BMSCs. Implantation of the complex hydrogel into a rat cranial defect model led to efficient bone regeneration compared to the rats treated with the hydrogel alone or with nHAP, indicating the simultaneous therapeutic effect of nHAP and PTH during the treatment process. Both the in vitro and in vivo results demonstrated that simultaneously incorporating nHAP and PTH into hydrogels shows promise for bone regeneration, suggesting a new strategy for tissue engineering and regeneration in the future.


Injectable muscle-adhesive antioxidant conductive photothermal bioactive nanomatrix for efficiently promoting full-thickness skeletal muscle regeneration.

  • Li Zhou‎ et al.
  • Bioactive materials‎
  • 2021‎

The completed skeletal muscle regeneration resulted from severe injury and muscle-related disease is still a challenge. Here, we developed an injectable muscle-adhesive antioxidant conductive bioactive photothermo-responsive nanomatrix for regulating the myogenic differentiation and promoting the skeletal muscle regeneration in vivo. The multifunctional nanomatrix was composed of polypyrrole@polydopamine (PPy@PDA, 342 ± 5.6 nm) nanoparticles-crosslinked Pluronic F-127 (F127)-polycitrate matrix (FPCP). The FPCP nanomatrix demonstrated inherent multifunctional properties including excellent photothermo-responsive and shear-thinning behavior, muscle-adhesive feature, injectable ability, electronic conductivity (0.48 ± 0.03 S/m) and antioxidant activity and photothermal function. The FPCP nanomatrix displayed better photothermal performance with near-infrared irradiation, which could provide the photo-controlled release of protein (91% ± 2.6% of BSA was released after irradiated 3 times). Additionally, FPCP nanomatrix could significantly enhance the cell proliferation and myogenic differentiation of mouse myoblast cells (C2C12) by promoting the expressions of myogenic genes (MyoD and MyoG) and myosin heavy chain (MHC) protein with negligible cytotoxicity. Based on the multifunctional properties, FPCP nanomatrix efficiently promoted the full-thickness skeletal muscle repair and regeneration in vivo, through stimulating the angiogenesis and myotube formation. This study firstly indicated the vital role of multifunctional PPy@PDA nanoparticles in regulating myogenic differentiation and skeletal muscle regeneration. This work also suggests that rational design of bioactive matrix with multifunctional feature would greatly enhance the development of regenerative medicine.


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