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Acta Biomaterialia

Raquel Costa-Almeida, Albina R Franco, Tamagno Pesqueira, Mariana B Oliveira, Pedro S Babo, Isabel B Leonor, João F Mano, Rui L Reis, Manuela E Gomes
Platelet-derived biomaterials are widely explored as cost-effective sources of therapeutic factors, holding a strong potential for endogenous regenerative medicine. Particularly for tendon repair, treatment approaches that shift the injury environment are explored to accelerate tendon regeneration. Herein, genipin-crosslinked platelet lysate (PL) patches are proposed for the delivery of human-derived therapeutic factors in patch augmentation strategies aiming at tendon repair. Developed PL patches exhibited a controlled release profile of PL proteins, including bFGF and PDGF-BB...
January 13, 2018: Acta Biomaterialia
Maria Chiara Ciuffreda, Giuseppe Malpasso, Cindy Chokoza, Deon Bezuidenhout, Kyle P Goetsch, Manuela Mura, Federica Pisano, Neil H Davies, Massimiliano Gnecchi
BACKGROUND: Mesenchymal stromal cells (MSC) repair infarcted hearts mainly through paracrine mechanisms. Low cell engraftment limits the release of soluble paracrine factors (SF) over time and, consequently, MSC efficacy. We tested whether a synthetic extracellular matrix mimic, a hydrogel containing heparin (H-HG), could ameliorate MSC engraftment and binding/release of SF, thus improving MSC therapy efficacy. METHODS AND RESULTS: In vitro, rat bone-marrow MSC (rBM-MSC) were seeded and grown into H-HG...
January 13, 2018: Acta Biomaterialia
T Paulraj, A V Riazanova, A J Svagan
Materials based on renewable biopolymers, selective permeability and stimuli-responsive release/loading properties play an important role in biomedical applications. Here, in order to mimic the plant primary cell-wall, microcapsules have been fabricated using cell wall polysaccharides, namely pectin, xyloglucan and cellulose nanofibers. For the first time, a large amount of xyloglucan was successfully included in such capsules. These capsules demonstrated stimuli-responsive (ON/OFF) permeability and biocompatibility...
January 13, 2018: Acta Biomaterialia
Fukai Ma, Feng Xu, Ronggang Li, Yongtao Zheng, Fan Wang, Naili Wei, Junjie Zhong, Qisheng Tang, Tongming Zhu, Zhifu Wang, Jianhong Zhu
Facial nerve injury caused by traffic accidents or operations may reduce the quality of life in patients, and recovery following the injury presents unique clinical challenges. Glial cell-derived neurotrophic factor (GDNF) is important in nerve regeneration; however, soluble GDNF rapidly diffuses into body fluids, making it difficult to achieve therapeutic efficacy. In this work, we developed a rat tail derived collagen conduit to connect nerve defects in a simple and safe manner. GDNF was immobilized in the collagen conduits via chemical conjugation to enable controlled release of GDNF...
January 9, 2018: Acta Biomaterialia
Shikha Chawla, Sourabh Ghosh
Current therapeutic strategies to reduce scarring in full thickness skin defect offer limited success due to poor understanding of scar tissue formation and the underlying signaling pathways. There is an urgent need to develop human cell based in vitro scar tissue models as animal testing is associated with ethical and logistic complications and inter-species variations. Pro-inflammatory cytokines play critical role in regulating scar development through complex interplay and interaction with the ECM and corresponding signaling pathways...
January 9, 2018: Acta Biomaterialia
Phillip L Lewis, Richard M Green, Ramille N Shah
Three dimensional (3D) printing is highly amenable to the fabrication of tissue-engineered organs of a repetitive microstructure such as the liver. The creation of uniform and geometrically repetitive tissue scaffolds can also allow for the control over cellular aggregation and nutrient diffusion. However, the effect of differing geometries, while controlling for pore size, has yet to be investigated in the context of hepatocyte function. In this study, we show the ability to precisely control pore geometry of 3D-printed gelatin scaffolds...
January 6, 2018: Acta Biomaterialia
Yuanheng Yang, Hang Lin, He Shen, Bing Wang, Guanghua Lei, Rocky S Tuan
Mesenchymal stem cell derived extracellular matrix (MSC-ECM) is a natural biomaterial with robust bioactivity and good biocompatibility, and has been studied as a scaffold for tissue engineering. In this investigation, we tested the applicability of using decellularized human bone marrow derived MSC-ECM (hBMSC-ECM) as a culture substrate for chondrocyte expansion in vitro, as well as a scaffold for chondrocyte-based cartilage repair. hBMSC-ECM deposited by hBMSCs cultured on tissue culture plastic (TCP) was harvested, and then subjected to a decellularization process to remove hBMSCs...
January 6, 2018: Acta Biomaterialia
Blanca González, Montserrat Colilla, Jaime Díez, Daniel Pedraza, Marta Guembe, Isabel Izquierdo-Barba, María Vallet-Regí
This work aims to provide an effective and novel solution for the treatment of infection by using nanovehicles loaded with antibiotics capable of penetrating the bacterial wall, thus increasing the antimicrobial effectiveness. These nanosystems, named "nanoantibiotics", are composed of mesoporous silica nanoparticles (MSNs), which act as nanocarriers of an antimicrobial agent (levofloxacin, LEVO) localized inside the mesopores. To provide the nanosystem of bacterial membrane interaction capability, a polycationic dendrimer, concretely the poly(propyleneimine) dendrimer of third generation (G3), was covalently grafted to the external surface of the LEVO-loaded MSNs...
January 4, 2018: Acta Biomaterialia
Huacheng He, Eleni Markoutsa, Jing Li, Peisheng Xu
Disulfiram (DSF), an FDA approved drug for the treatment of alcoholism, degrades to therapeutically active diethyldithiocarbamate (DDTC) in the body by reduction. Hereby, we developed a redox sensitive DDTC-polymer conjugate for targeted cancer therapy. It was found that the DDTC-polymer conjugate modified with a β-D-galactose receptor targeting ligand can self-assemble into LDNP nanoparticle and efficiently enter cancer cells by receptor-mediated endocytosis. Upon cellular uptake, the LDNP nanoparticle degrades and releases DDTC due to the cleavage of disulfide bonds, and subsequently forms copper (II) DDTC complex to kill a broad spectrum of cancer cells...
December 30, 2017: Acta Biomaterialia
Chenchen Zhao, Shengyu Wang, Gangliang Wang, Mingzhen Su, Liyang Song, Jiaxin Chen, Shunwu Fan, Xianfeng Lin
Muscle injury and defect affect people's quality of life, and effective treatment is lacking. Herein, we generated a scaffold to obtain decellularized porcine Achilles tendon myotendinous junction (D-MTJ) extracellular matrix (ECM) with well-preserved native biphasic hierarchical structure, biological composition, and excellent mechanical properties for muscle regeneration. The combined use of potassium chloride, potassium iodide, Triton-X 100, and sodium-dodecyl sulfate (SDS) can completely remove the main immunogenicity, while maintaining the major biological components and microstructure...
December 30, 2017: Acta Biomaterialia
P G Dixon, J T Muth, X Xiao, M A Skylar-Scott, J A Lewis, L J Gibson
Bamboo is a sustainable, lightweight material that is widely used in structural applications. To fully develop micromechanical models for plants, such as bamboo, the mechanical properties of each individual type of tissue are needed. However, separating individual tissues and testing them mechanically is challenging. Here, we report an alternative approach in which micro X- ray computed tomography (µ-CT) is used to image moso bamboo (Phyllostachys pubescens). The acquired images, which correspond to the 3D structure of the parenchyma, are then transformed into physical, albeit larger scale, structures by 3D printing, and their mechanical properties are characterized...
December 30, 2017: Acta Biomaterialia
Diana G Soares, Zhanpeng Zhang, Fatma Mohamed, Thomas W Eyster, Carlos A de Souza Costa, Peter X Ma
In this study, we investigated the anti-inflammatory, odontogenic and pro-angiogenic effects of integrating simvastatin and nanofibrous poly(l-lactic acid) (NF-PLLA) scaffolds on dental pulp cells (DPCs). Highly porous NF-PLLA scaffolds that mimic the nanofibrous architecture of extracellular matrix were first fabricated, then seeded with human DPCs and cultured with 0.1 μM simvastatin and/or 10 μg/mL pro-inflammatory stimulator lipopolysaccharide (LPS). The gene expression of pro-inflammatory mediators (TNF-α, IL-1β and MMP-9 mRNA) and odontoblastic markers (ALP activity, calcium content, DSPP, DMP-1 and BMP-2 mRNA) was quantified after long-term culture in vitro...
December 30, 2017: Acta Biomaterialia
Fangfang Xia, Wenxiu Hou, Chunlei Zhang, Xiao Zhi, Jin Cheng, Jesus Martinez de la Fuente, Jie Song, Daxiang Cui
Nanoparticle-based drug delivery systems have drawn a great deal of attention for their opportunities to improve cancer treatments over intrinsic limits of conventional cancer therapies. Herein, we developed the polypeptide-modified gold nanoclusters (GNCs)-based nanoprobes for tumor-targeted near-infrared fluorescence imaging and chemo-photodynamic therapy. The nanoprobes comprise of tetra-functional components: i) polyethylene glycol (PEG) shell for long blood circulation and better biocompatibility; ii) MMP2 polypeptide (CPLGVRGRGDS) for tumor targeting; iii) cis-aconitic anhydride-modified doxorubicin (CAD) for pH-sensitive drug release; iv) photosensitizer chlorin e6 (Ce6) for photodynamic therapy and fluorescence imaging...
December 29, 2017: Acta Biomaterialia
Hanh Thuy Nguyen, Cao Dai Phung, Raj Kumar Thapa, Tung Thanh Pham, Tuan Hiep Tran, Jee-Heon Jeong, Sae Kwang Ku, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
Lanreotide (LT), a synthetic analog of somatostatin, has been demonstrated to specifically bind to somatostatin receptors (SSTRs), which are widely overexpressed in several types of cancer cells. In this study, we incorporated a chemotherapeutic agent, methotrexate (MTX), and a photosensitizer material, polyaniline (PANI), into hybrid polymer nanoparticles (NPs), which could target cancer cells after conjugation with LT (LT-MTX/PANI NPs). The successful preparation of LT-MTX/PANI NPs was confirmed by a small particle size (187...
December 29, 2017: Acta Biomaterialia
Ethan M Lotz, Michael B Berger, Zvi Schwartz, Barbara D Boyan
A critical stage during osseointegration of a titanium (Ti) implant is primary bone remodeling, which involves cross talk among osteoclast precursors, osteoclasts, mesenchymal stem cells (MSCs), and osteoblasts. This phase couples the processes of bone formation and resorption. During remodeling, osteoclasts produce factors capable of regulating MSC migration and osteogenesis. Furthermore, they degrade primary bone, creating a foundation with a specific chemistry, stiffness, and morphology for osteoblasts to synthesize and calcify their matrix...
December 29, 2017: Acta Biomaterialia
Torri E Rinker, Brandon D Philbrick, Marian H Hettiaratchi, David M Smalley, Todd C McDevitt, Johnna S Temenoff
Protein delivery is often used in tissue engineering applications to control differentiation processes, but is limited by protein instability and cost. An alternative approach is to control the cellular microenvironment through biomaterial-mediated sequestration of cell-secreted proteins important to differentiation. Thus, we utilized heparin-based microparticles to modulate cellular differentiation via protein sequestration in an in vitro model system of endochondral ossification. Heparin and poly(ethylene-glycol) (PEG; a low-binding material control)-based microparticles were incorporated into ATDC5 cell spheroids or incubated with ATDC5 cells in transwell culture...
December 29, 2017: Acta Biomaterialia
Henry W Haslach, Ahmed Siddiqui, Amanda Weerasooriya, Ryan Nguyen, Jacob Roshgadol, Noel Monforte, Eileen McMahon
This experimental study adopts a fracture mechanics strategy to investigate the mechanical cause of aortic dissection. Inflation of excised healthy bovine aortic rings with a cut longitudinal notch that extends into the media from the intima suggests that an intimal tear may propagate a nearly circumferential-longitudinal rupture surface that is similar to the delamination that occurs in aortic dissection. Radial and 45°-from-radial cut notch orientations, as seen in the thickness surface, produce similar circumferential crack propagation morphologies...
December 29, 2017: Acta Biomaterialia
Neil M Dold, Qin Zeng, Xiangbin Zeng, Christopher M Jewell
Nucleic acid delivery vehicles are poised to play an important role in delivering gene therapy for vaccines and immunotherapies, and in delivering nucleic acid based adjuvants. A number of common polymeric delivery vehicles used in nucleic acid delivery have recently been shown to interact with immune cells and directly stimulate immunogenic responses, particularly in particle form. Poly(beta-amino esters) were designed for nucleic acid delivery and have demonstrated promising performance in a number of vaccine and therapeutic studies...
December 29, 2017: Acta Biomaterialia
Andrew L Lakes, Carolyn T Jordan, Prachi T Gupta, David A Puleo, J Zach Hilt, Thomas D Dziubla
Recently, biomaterials have been designed to contain redox-sensitive moieties, such as thiols and disulfides, to impart responsive degradation and/or controlled release. However, due to the high sensitivity of cellular redox-based systems which maintain free-radical homeostasis (e.g. glutathione/glutathione disulfide), if these biomaterials modify the cellular redox environment, they may inadvertently affect cellular compatibility and/or oxidative stress defenses. In this work, we hypothesize that the degradation products of a poly(β-amino ester) (PBAE) hydrogel formed with redox sensitive disulfide (cystamine) crosslinking could serve as a supplement to the environmental cellular antioxidant defenses...
December 28, 2017: Acta Biomaterialia
Victor Balashov, Anton Efimov, Olga Agapova, Alexander Pogorelov, Igor Agapov, Konstantin Agladze
Building functional and robust scaffolds for engineered biological tissue requires a nanoscale mechanistic understanding of how cells use the scaffold for their growth and development. A vast majority of the scaffolds used for cardiac tissue engineering are based on polymer materials, the matrices of nanofibers. Attempts to load the polymer fibers of the scaffold with additional sophisticated features, such as electrical conductivity and controlled release of the growth factors or other biologically active molecules, as well as trying to match the mechanical features of the scaffold to those of the extracellular matrix, cannot be efficient without a detailed knowledge of how the cells are attached and strategically positioned with respect to the scaffold nanofibers at micro and nanolevel...
December 27, 2017: Acta Biomaterialia
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