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Shah N.J.,Massachusetts Institute of Technology | Hyder Md.N.,Massachusetts Institute of Technology | Moskowitz J.S.,Massachusetts Institute of Technology | Quadir M.A.,Massachusetts Institute of Technology | And 8 more authors.
Science Translational Medicine | Year: 2013

The functional success of a biomedical implant critically depends on its stable bonding with the host tissue. Aseptic implant loosening accounts for more than half of all joint replacement failures. Various materials, including metals and plastic, confer mechanical integrity to the device, but often these materials are not suitable for direct integration with the host tissue, which leads to implant loosening and patient morbidity. We describe a self-assembled, osteogenic, polymer-based conformal coating that promotes stable mechanical fixation of an implant in a surrogate rodent model. A single modular, polymer-based multilayered coating was deposited using a water-based layer-by-layer approach, by which each element was introduced on the surface in nanoscale layers. Osteoconductive hydroxyapatite (HAP) and osteoinductive bone morphogenetic protein-2 (BMP-2) contained within the nanostructured coating acted synergistically to induce osteoblastic differentiation of endogenous progenitor cells within the bone marrow, without indications of a foreign body response. The tuned release of BMP-2, controlled by a hydrolytically degradable poly(β-amino ester), was essential for tissue regeneration, and in the presence of HAP, the modular coating encouraged the direct deposition of highly cohesive trabecular bone on the implant surface. In vivo, the bone-implant interfacial tensile strength was significantly higher than standard bioactive bone cement, did not fracture at the interface, and had long-term stability. Collectively, these results suggest that the multilayered coating system promotes biological fixation of orthopedic and dental implants to improve surgical outcomes by preventing loosening and premature failure. Copyright © 2013 by the American Association for the Advancement of Science; all rights reserved. Source


Chen C.,Chongqing Medical University | Chen C.,Harvard University | Xie J.,University of Sichuan | Rajappa R.,Tissue Engineering Laboratories | And 4 more authors.
Acta Biochimica et Biophysica Sinica | Year: 2015

Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are major proinflammatory cytokines involved in osteoarthritis (OA). These cytokines disturb chondrocyte metabolism by suppressing the synthesis of extracellular matrix proteins and stimulating the release of catabolic proteases, but little is known about their role in chondrocyte mechanics. Thus, the aim of this study was to measure the effects of IL-1β and TNF-α on the mechanical properties of the chondrocytes. Chondrocytes from goat knee joints were cultured in 96-well plates. The cellular stiffness and contractile function were probed using optical magnetic twisting cytometry, the cytoskeleton and the expression of extracellular matrix proteins were visualized using immunofluorescent staining, and chondrocyte phenotypical expression was measured by western blot analysis. Results showed that chondrocyte stiffness was dramatically decreased by disruption of F-actin but was unaffected by disruption of the intermediate filament vimentin. Treatment with 10 ng/ml IL-1β or 40 ng/ml TNF-α for 24 h substantially increased the expression level of F-actin and cellular stiffness, and impaired cell stiffening in response to the contractile agonist histamine, but these effects were blocked by the Rho-associated protein kinase inhibitor Y27632. In conclusion, IL-1β and TNF-α substantially change the mechanical properties of the chondrocytes in vitro. While changes of chondrocyte mechanics in vivo during OA progression remain unclear, this finding reveals a prominent role of these cytokines in cellular mechanics and provides insight for anti-cytokine therapies of OA. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. Source


Toh W.S.,National University of Singapore | Toh W.S.,Tissue Engineering Laboratories | Toh W.S.,Harvard University | Lee E.H.,National University of Singapore | Cao T.,National University of Singapore
Stem Cell Reviews and Reports | Year: 2011

The current surgical intervention of using autologous chondrocyte implantation (ACI) for cartilage repair is associated with several problems such as donor site morbidity, de-differentiation upon expansion and fibrocartilage repair following transplantation. This has led to exploration of the use of stem cells as a model for chondrogenic differentiation as well as a potential source of chondrogenic cells for cartilage tissue engineering and repair. Embryonic stem cells (ESCs) are advantageous, due to their unlimited self-renewal and pluripotency, thus representing an immortal cell source that could potentially provide an unlimited supply of chondrogenic cells for both cell and tissue-based therapies and replacements. This review aims to present an overview of emerging trends of using ESCs in cartilage tissue engineering and regenerative medicine. In particular, we will be focusing on ESCs as a promising cell source for cartilage regeneration, the various strategies and approaches employed in chondrogenic differentiation and tissue engineering, the associated outcomes from animal studies, and the challenges that need to be overcome before clinical application is possible. © 2010 Springer Science+Business Media, LLC. Source


Elias P.Z.,Harvard-MIT Division of Health Sciences and Technology | Elias P.Z.,Tissue Engineering Laboratories | Spector M.,Tissue Engineering Laboratories | Spector M.,Harvard University
Journal of Neurotrauma | Year: 2012

Penetrating brain injury (PBI) encountered in both the military and civilian sectors results in high morbidity and mortality due to the absence of effective treatment options for survivors of the initial trauma. Developing therapies for such injuries requires a better understanding of the complex pathology involved when projectiles enter the skull and disrupt the brain parenchyma. This study presents a histological characterization of bilateral PBI using a relatively new injury model in the rat, and also investigates the implantation of a collagen scaffold into the PBI lesion as a potential treatment option. At 1 week post-PBI, the lesion was characterized by dense macrophage infiltration, evolving astrogliosis, hypervascularity, and an absence of viable neurons, oligodendrocytes, and myelinated axons. Histomorphometric analysis revealed that the PBI lesion volume expanded by 29% between 1 week and 5 weeks post-injury, resulting in formation of a large acellular cavity. Immunohistochemistry showed a decrease in the presence of CD68-positive macrophages from 1 to 5 weeks post-PBI as the necrotic tissue in the lesion was cleared, while persistent glial scarring remained in the form of upregulated GFAP expression surrounding the PBI cavity. Implanted type I collagen scaffolds remained intact with open pores after time periods of 1 week and 4 weeks in vivo, and were found to be sparsely infiltrated with macrophages, astrocytes, and endothelial cells. Collagen scaffolds appear to be an appropriate delivery vehicle for cellular and pharmacological therapeutic agents in future studies of PBI. © Copyright 2012, Mary Ann Liebert, Inc. Source


Elias P.Z.,Tissue Engineering Laboratories | Elias P.Z.,Harvard-MIT Division of Health Sciences and Technology | Spector M.,Tissue Engineering Laboratories | Spector M.,Harvard University
Journal of the Mechanical Behavior of Biomedical Materials | Year: 2012

In the field of tissue engineering and regenerative medicine for the central nervous system, therapeutic strategies may involve implantation of biomaterial scaffolds into the brain. An understanding of the relationship between the brain and the scaffold mechanical properties can help in the selection of a safe and effective biomaterial. This research demonstrates the use of indentation testing along with viscoelastic modeling to characterize and compare mechanical properties of in situ rat cerebral cortex and collagen scaffolds of varying collagen concentration. The stress-relaxation solution for indentation of a viscoelastic material was derived based on a five-element Maxwell model and use of the correspondence principle. Applying the model to experimental stress-relaxation data, the brain was characterized by three shear moduli G1=1.6±0.10kPa, G2=2.0±0.15kPa, G3=1.8±0.20kPa, and two viscosities n2=11.0±0.44kPa{dot operator}s, n3=148.7±6.70kPa{dot operator}s, with corresponding relaxation time constants τ1=5.7±0.3s and τ2=88.4±7.6s. The brain showed average relaxation of 74% from its peak force during loading to an approximately asymptotic force over a 5 minute hold at constant displacement. Collagen scaffolds generally showed increasing trends in the shear moduli, viscosities, and percentage relaxation with increasing collagen concentration. While the brain had similar stiffness to the 1.0% collagen scaffold during the loading phase, the brain's relaxation behavior was distinct from all of the scaffolds. Similarities and differences between the mechanical behavior of the brain and collagen scaffolds of varying collagen concentration are discussed in relation to application of biomaterials for regenerative medicine. © 2012 Elsevier Ltd. Source

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