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Acta Biomaterialia

Feihu Wang, Qian Huang, Yun Wang, Wenjun Zhang, Ran Lin, Yanna Yu, Yuanyuan Shen, Honggang Cui, Shengrong Guo
Simultaneous inhibition of both tumor growth and metastasis is the key to treating metastatic cancer, yet the development of effective drug delivery systems represents a great challenge since multimodal therapeutic agents must be rationally combined to overcome the biological mechanisms underpinning tumor cell proliferation and invasion. In this context, we report a hybrid therapeutic nanoscale platform that incorporates an anti-proliferative drug, doxorubicin (DOX), and an anti-NF-κB agent, p65-shRNA, for effective treatment of metastatic breast cancer...
July 13, 2018: Acta Biomaterialia
Fanyi Li, Vinh X Truong, Philipp Fisch, Clara Levinson, Veronica Glattauer, Marcy Zenobi-Wong, Helmut Thissen, John S Forsythe, Jessica E Frith
Current clinical approaches to treat articular cartilage degeneration provide only a limited ability to regenerate tissue with long-term durability and functionality. In this application, injectable bulk hydrogels and microgels containing stem cells can provide a suitable environment for tissue regeneration. However insufficient cell-cell interactions, low differentiation efficiency and poor tissue adhesion hinder the formation of high-quality hyaline type cartilage. Here, we have designed a higher order tissue-like structure using injectable cell-laden microgels as the building blocks to achieve human bone marrow-derived mesenchymal stem cell (hBMSC) long-term maintenance and chondrogenesis...
July 10, 2018: Acta Biomaterialia
Sun-Min Yu, Jung Min Oh, Junwon Lee, Whaseon Lee-Kwon, Woonggyu Jung, François Amblard, Steve Granick, Yoon-Kyoung Cho
The unique structure of kidney tubules is representative of their specialized function. Because maintaining tubular structure and controlled diameter is critical for kidney function, it is critical to understand how topographical cues, such as curvature, might alter cell morphology and biological characteristics. Here, we examined the effect of substrate curvature on the shape and phenotype of two kinds of renal epithelial cells (MDCK and HK-2) cultured on a microchannel with a broad range of principal curvature...
July 10, 2018: Acta Biomaterialia
Nicolas Broguiere, Florian Formica, Gonçalo Barreto, Marcy Zenobi-Wong
The bacterial ligase Sortase A (SA) and its mutated variants have become increasingly popular over the last years for post-translational protein modifications due to their unparalleled specificity and efficiency. The aim of this work was to study SA as a cross-linking enzyme for hydrogel-based tissue engineering. For this, we optimized SA pentamutant production and purification from E. coli to achieve high yields and purity. Then using hyaluronan (HA) as a model biopolymer and modifying it with SA-substrate peptides, we studied the cross-linking kinetics obtained with SA, the enzyme stability, cytocompatibility, and immunogenicity, and compared those to state-of-the-art standards...
July 10, 2018: Acta Biomaterialia
Meili Hou, Yong-E Gao, Xiaoxiao Shi, Shuang Bai, Xiaoqian Ma, Baosheng Li, Bo Xiao, Peng Xue, Yuejun Kang, Zhigang Xu
The goal of nanomedicine is to seek strategies that are more efficient to address various limitations and challenges faced by conventional medicines, including lack of target specificity, poor bioavailability, premature degradability, and undesired side effects. Self-assembling drug amphiphiles represent a prospective nanomedicine for cancer therapy owing to their favorable route of administration and therapeutic efficiency compared with pristine drug counterparts. In this work, we report a class of self-deliverable prodrug amphiphiles consisting of the hydrophilic drug methotrexate (MTX) and the hydrophobic anticancer drugs camptothecin (CPT) and doxorubicin (DOX) for targeted and combinational chemotherapy...
July 10, 2018: Acta Biomaterialia
Cristina González-García, Marco Cantini, José Ballester-Beltrán, George Altankov, Manuel Salmerón-Sánchez
Extracellular matrix (ECM) proteins are key mediators of cell/material interactions. The surface density and conformation of these proteins adsorbed on the material surface influence cell adhesion and the cellular response. We have previously shown that subtle variations in surface chemistry lead to drastic changes in the conformation of adsorbed fibronectin (FN). On poly(ethyl acrylate) (PEA), FN unfolds and displays domains for cell adhesion and FN-FN interaction, whereas on poly(methyl acrylate) (PMA) - with only one methyl group less - FN remains globular as it is in solution...
July 10, 2018: Acta Biomaterialia
Yanbo Zhang, Jin Zhang, Weiguo Xu, Gao Xiao, Jianxun Ding, Xuesi Chen
Topical chemotherapy with complementary drugs is one of the most promising strategies to achieve an effective antitumor activity. Herein, a synergistic strategy for hepatoma therapy by the combination of tumor microenvironment-sensitive polymer-doxorubicin (DOX) conjugate thermogel, containing a DNA intercalator DOX, and docetaxel (DTX), a microtubule-interfering agent, was proposed. First, cis-aconitic anhydride-functionalized DOX (CAD) and succinic anhydride-modified DOX (SAD) were conjugated onto the terminal hydroxyl groups of poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG-PLGA), yielding the acid-sensitive CAD-PLGA-PEG-PLGA-CAD and the insensitive SAD-PLGA-PEG-PLGA-SAD conjugates, respectively...
July 10, 2018: Acta Biomaterialia
Chao Han, Can Zhang, Ting Ma, Chao Zhang, Jianguang Luo, Xiao Xu, Huijun Zhao, Yan Chen, Lingyi Kong
Effective targeting of mitochondria has emerged as a beneficial strategy in cancer therapy. However, the development of mitochondria-targeting ligands is difficult because of the low permeability of the mitochondrial double membrane. We found that hypericin (HY), a natural product isolated from Hypericum perforatum L., is an effective mitochondria-targeting ligand. HY-functionalized graphene oxide (GO) loaded with doxorubicin (GO-PEG-SS-HY/DOX) increased the synergistic anticancer efficacy of phototherapy and chemotherapy in the absence of apparent adverse side effects...
July 10, 2018: Acta Biomaterialia
Sandra L Arias, Akshath Shetty, Joshua Devorkin, Jean-Paul Allain
Tissue-engineered vascular grafts (TEVG) use biologically-active cells with or without supporting scaffolds to achieve tissue remodeling and regrowth of injured blood vessels. However, this process may take several weeks because the high hemodynamic shear stress at the damaged site causes cellular denudation and impairs tissue regrowth. We hypothesize that a material with magnetic properties can provide the force required to speed up re-endothelization at the vascular defect by facilitating high cell density coverage, especially during the first 24 hours after implantation...
July 9, 2018: Acta Biomaterialia
F Veronesi, M Fini, M Sartori, A Parrilli, L Martini, M Tschon
Wear-mediated osteolysis is a common complication occurring around implanted prosthesis, which ultimately leads to bone loss with mechanical instability and the need for surgical revision. At the moment, revision surgery is the only effective treatment. The aim of this study was to assess the efficacy of pulsed electromagnetic fields (PEMFs) and platelet rich plasma (PRP), alone and in association, in a clinically relevant in vivo model of periprosthetic osteolysis. Titanium alloy pins were implanted intramedullary in distal femurs of male inbred rats and, after osseointegration, polyethylene particles were injected intra-articularly to induce osteolysis...
July 6, 2018: Acta Biomaterialia
Y Li, H Jahr, K Lietaert, P Pavanram, A Yilmaz, L I Fockaert, M A Leeflang, B Pouran, Y Gonzalez-Garcia, H Weinans, J M C Mol, J Zhou, A A Zadpoor
Additively manufactured (AM) topologically ordered porous metallic biomaterials with the proper biodegradation profile offer a unique combination of properties ideal for bone regeneration. These include a fully interconnected porous structure, bone-mimicking mechanical properties, and the possibility of fully regenerating bony defects. Most of such biomaterials are, however, based on magnesium and, thus, degrade too fast. Here, we present the first report on topologically ordered porous iron made by Direct Metal Printing (DMP)...
July 5, 2018: Acta Biomaterialia
R C Cornelison, S M Wellman, J H Park, S L Porvasnik, Y H Song, R A Wachs, C E Schmidt
Preservation of tissue structure is often a primary goal when optimizing tissue and organ decellularization methods. Many current protocols nonetheless rely on detergents that aid extraction of cellular components but also damage tissue architecture. It may be more beneficial to leverage an innate cellular process such as apoptosis and promote cell removal without the use of damaging reagents. During apoptosis, a cell detaches from the extracellular matrix, degrades its internal components, and fragments its contents for easier clearance...
July 5, 2018: Acta Biomaterialia
Christoph Lauer, Stefanie Schmier, Thomas Speck, Klaus G Nickel
According to the Weibull theory for brittle materials, the mean experimental strength decreases with test specimen size. For the brittle parts of an organism this would mean that becoming larger in size results automatically in reducing strength. This unfavorable relationship was investigated for two porous, biological materials that are promising concept generators for crack deflective and energy dissipative applications in compressive overloading: the quasi-brittle coconut endocarp and the brittle spines of the sea urchin Heterocentrotus mamillatus...
July 4, 2018: Acta Biomaterialia
Yong Hou, Wenyan Xie, Katharina Achazi, Jose Luis Cuellar-Camacho, Matthias F Melzig, Wei Chen, Rainer Haag
The direct injection of bone marrow mesenchymal stem cells (hMSCs) is a promising strategy for bone tissue engineering applications. Herein, we have developed injectable degradable poly(vinyl alcohol) (PVA) microgels loaded with hMSCs and growth factors and prepared by a high-throughput microfluidic technology. The PVA-based microgels with tunable mechanical and degradable properties were composed of vinyl ether acrylate-functionalized PVA (PVA-VEA) and thiolated PVA-VEA (PVA-VEA-SH) through a Michael-type crosslinking reaction under mild conditions...
July 4, 2018: Acta Biomaterialia
Yu Moriguchi, Brandon Borde, Connor Berlin, Christoph Wipplinger, Stephen R Sloan, Sertac Kirnaz, Brenton Pennicooke, Rodrigo Navarro-Ramirez, Thamina Khair, Peter Grunert, Eliana Kim, Lawrence Bonassar, Roger Härtl
OBJECTIVE: The aim is assessing the in vivo efficacy of annulus fibrosus (AF) cells seeded into collagen by enhancing the reparative process around annular defects and preventing further degeneration in a rat-tail model. SUMMARY OF BACKGROUND DATA: Treating disc herniation with discectomy may relieve the related symptoms but does not address the underlying pathology. The persistent annular defect may lead to re-herniation and further degeneration. We recently demonstrated that riboflavin crosslinked high-density collagen gels (HDC) can facilitate annular repair in vivo...
July 4, 2018: Acta Biomaterialia
Mengqian Liu, Manando Nakasaki, Yu-Ru Vernon Shih, Shyni Varghese
Emerging studies show the potential application of synthetic biomaterials that are intrinsically osteoconductive and osteoinductive as bone grafts to treat critical bone defects. Here, the biomaterial not only assists recruitment of endogenous cells, but also supports cellular activities relevant to bone tissue formation and function. While such biomaterial-mediated in situ tissue engineering is highly attractive, success of such an approach relies largely on the regenerative potential of the recruited cells, which is anticipated to vary with age...
June 29, 2018: Acta Biomaterialia
N Gómez-Cerezo, E Verron, V Montouillout, F Fayon, P Lagadec, J M Bouler, B Bujoli, D Arcos, M Vallet-Regí
Mesoporous bioactive glasses (MBGs) in the system SiO2 -CaO-P2 O5 -Ga2 O3 have been synthesized by the evaporation induced self-assembly method and subsequent impregnation with Ga cations. Two different compositions have been prepared and the local environment of Ga(III) has been characterized using 29 Si, 71 Ga and 31 P NMR analysis, demonstrating that Ga(III) is efficiently incorporated as both, network former (GaO4 units) and network modifier (GaO6 units). In vitro bioactivity tests evidenced that Ga-containing MBGs retain their capability for nucleation and growth of an apatite-like layer in contact with a simulated body fluid with ion concentrations nearly equal to those of human blood plasma...
June 29, 2018: Acta Biomaterialia
Tingting Lv, Ziying Li, Liang Xu, Yingying Zhang, Haijun Chen, Yu Gao
Although novel molecular targeted drugs have been recognized as an effective therapy for non-small lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutations, their efficacy fails to meet the expectation due to the acquired resistance in tumors. Up-regulation of the anti-apoptotic protein Survivin was shown to contribute to the resistance to EGFR tyrosine kinase inhibitors (TKI) in EGFR mutation-positive NSCLC. However, the unorganized tumors blood vessels impeded drug penetration into tumor tissue and the resulting insufficient intracellular drug/gene delivery in drug-resistant cancer cells remarkably weakened the drug efficacy in NSCLC...
June 27, 2018: Acta Biomaterialia
William K Grier, Aleczandria S Tiffany, Matthew D Ramsey, Brendan A C Harley
The development of biomaterials for a range of tissue engineering applications increasingly requires control over the bioavailability of biomolecular cues such as growth factors in order to promote desired cell responses. While efforts have predominantly concentrated on covalently-bound or freely-diffusible incorporation of biomolecules in porous, three-dimensional biomaterials, opportunities exist to exploit transient interactions to concentrate growth factor activity over desired time frames. Here, we report the incorporation of β-cyclodextrin into a model collagen-GAG scaffold as a means to exploit the passive sequestration and release of growth factors via guest-host interactions to control mesenchymal stem cell differentiation...
June 23, 2018: Acta Biomaterialia
Zhilu Yang, Hua Qiu, Xiangyang Li, Peng Gao, Nan Huang
A novel concept of generating therapeutic gas, nitric oxide (NO) via catalytic phenolic-amine "gallolamine" surface chemistry is developed. The concept is realized using plant polyphenol, gallic acid, and a glutathione peroxidase-like organoselenium compound cystamine or selenocystamine through one-step phenol-amine molecular assembling process. The resulting NO-generating coating with phenolic-cystamine or -selenocystamine framework showed the ability for long-term, steady and controllable range of NO release rates being unparalleled with any existing NO-releasing or NO-generating surface engineering toolkits...
June 23, 2018: Acta Biomaterialia
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