| Reportlinker Adds Stem Cell Therapy for Peripheral Arterial Disease
January 7, 2010 at 2:39 pm
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| Elsevier's 'Article of the Future' is now available for all Cell Press journals
January 7, 2010 at 2:39 pm
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| Biologists develop efficient genetic modification of human embryonic stem cells
January 7, 2010 at 1:39 pm
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| Lentivirus Immobilization to Nanoparticles for Enhanced and Localized Delivery From Hydrogels.
January 7, 2010 at 6:21 am
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| | Lentivirus Immobilization to Nanoparticles for Enhanced and Localized Delivery From Hydrogels. Mol Ther. 2010 Jan 5; Authors: Shin S, Shea LD Hydrogels can provide a controllable cell microenvironment for numerous applications in regenerative medicine, and delivery of gene therapy vectors can be employed to enhance their bioactivity. We investigated the delivery of lentiviral vectors from hydrogels, and employed the immobilization of lentivirus to hydroxylapatite (HA) nanoparticles as a means to retain and stabilize vectors within hydrogels, and thereby increase delivery efficiency. Entrapment of the vector alone within the hydrogel maintained the activity of the virus more effectively compared to the absence of a hydrogel, and release was slowed with an increasing solid content of the hydrogel. Association of the lentivirus with HA increased the activity of the complexes, with HA increasing the virus activity for 72 hours. Cells seeded onto lentivirus-HA-loaded hydrogels had a decreased number of infected cells outside of the hydrogel relative to the absence of HA. In vivo studies with collagen hydrogels loaded with lentivirus and HA-lentivirus demonstrated sustained and localized transgene expression for at least 4 weeks, with increased expression using the lentivirus-HA complex. This strategy of nanoparticle immobilization to stabilize and retain vectors is broadly applicable to hydrogels, and may provide a versatile tool to combine gene therapy and biomaterials for applications in regenerative medicine. PMID: 20051940 [PubMed - as supplied by publisher] |
| Unique Modulation of Cadherin Expression Pattern during Posterior Frontal Cranial Suture Development and Closure.
January 7, 2010 at 6:21 am
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| | Unique Modulation of Cadherin Expression Pattern during Posterior Frontal Cranial Suture Development and Closure. Cells Tissues Organs. 2009 Dec 24; Authors: Sahar DE, Behr B, Fong KD, Longaker MT, Quarto N Cranial suture development involves coordinated expression of multiple genes and tissue contribution from neural crest cells and paraxial mesoderm for timely sutural morphogenesis. Transcription factors, growth factors, and neural crest determinant genes play critical roles in calvarial growth ensuring normal development of the underlying brain. In vitro studies have implicated cell-cell adhesion molecules as a driving force behind suture closure. We performed cDNA microarray to study differential expression of adhesion molecules during the timing of suture closure in a mouse model where only the posterior frontal (PF) suture closes. Our results indicate increased expression of E-cadherin during the period of PF suture closure. Quantitative RT-PCR analysis of E- and N-cadherin in PF closing suture revealed a biphasic expression of N-cadherin, the first phase coinciding with cellular condensation preceding chondrogenesis followed by a second phase coinciding with E-cadherin co-expression and suture closure. Furthermore, expression analysis of the N-cadherin and E-cadherin transcriptional repressors Wnt7a and Snail indicate a specific temporal regulation of these genes, suggesting their potential role as regulators of both E- and N-cadherin during the PF suture development and closure. Finally, given the in vitro evidence of fibroblast growth factor (FGF)-2 as a potential regulator of E- and N-cadherin we investigated the expression of E-cadherin during PF suture closure in Fgf-2 deficient mice. In contrast to in vitrodata previously reported, E-cadherin expression is normal in these animals, and PF suture closure occurs properly, probably due to potential redundancy of FGF ligands ensuring normal temporal expression of E-cadherin and PF suture closure. PMID: 20051668 [PubMed - as supplied by publisher] |
| Progress toward the clinical application of patient-specific pluripotent stem cells.
January 7, 2010 at 6:21 am
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| | Progress toward the clinical application of patient-specific pluripotent stem cells. J Clin Invest. 2010 Jan;120(1):51-9 Authors: Kiskinis E, Eggan K Induced pluripotent stem (iPS) cells are generated by epigenetic reprogramming of somatic cells through the exogenous expression of transcription factors. These cells, just like embryonic stem cells, are likely to have a major impact on regenerative medicine, because they self-renew and retain the potential to be differentiated into all cell types of the human body. In this Review, we describe the current state of iPS cell technology, including approaches by which they are generated and what is known about their biology, and discuss the potential applications of these cells for disease modeling, drug discovery, and, eventually, cell replacement therapy. PMID: 20051636 [PubMed - in process] |
| Pregenerative medicine: developmental paradigms in the biology of cardiovascular regeneration.
January 7, 2010 at 6:21 am
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| | Pregenerative medicine: developmental paradigms in the biology of cardiovascular regeneration. J Clin Invest. 2010 Jan;120(1):20-8 Authors: Yi BA, Wernet O, Chien KR The ability to create new functional cardiomyocytes is the holy grail of cardiac regenerative medicine. From studies using model organisms, new insights into the fundamental pathways that drive heart muscle regeneration have begun to arise as well as a growing knowledge of the distinct families of multipotent cardiovascular progenitors that generate diverse lineages during heart development. In this Review, we highlight this intersection of the "pregenerative" biology of heart progenitor cells and heart regeneration and discuss the longer term challenges and opportunities in moving toward a therapeutic goal of regenerative cardiovascular medicine. PMID: 20051633 [PubMed - in process] |
| Repairing skeletal muscle: regenerative potential of skeletal muscle stem cells.
January 7, 2010 at 6:21 am
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| | Repairing skeletal muscle: regenerative potential of skeletal muscle stem cells. J Clin Invest. 2010 Jan;120(1):11-9 Authors: Tedesco FS, Dellavalle A, Diaz-Manera J, Messina G, Cossu G Skeletal muscle damaged by injury or by degenerative diseases such as muscular dystrophy is able to regenerate new muscle fibers. Regeneration mainly depends upon satellite cells, myogenic progenitors localized between the basal lamina and the muscle fiber membrane. However, other cell types outside the basal lamina, such as pericytes, also have myogenic potency. Here, we discuss the main properties of satellite cells and other myogenic progenitors as well as recent efforts to obtain myogenic cells from pluripotent stem cells for patient-tailored cell therapy. Clinical trials utilizing these cells to treat muscular dystrophies, heart failure, and stress urinary incontinence are also briefly outlined. PMID: 20051632 [PubMed - in process] |
| Cardiomyocyte proliferation: paving the way to cardiac regenerative medicine without stem cell transplantation.
January 7, 2010 at 6:21 am
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| | Cardiomyocyte proliferation: paving the way to cardiac regenerative medicine without stem cell transplantation. Cardiovasc Res. 2010 Jan 5; Authors: Ventura C PMID: 20051386 [PubMed - as supplied by publisher] |
| Proceedings of the Symposium on the Mechanics of Growth and Remodeling in Native and Engineered Tissues. Marco Island, Florida, USA. June 25-29, 2008.
January 7, 2010 at 6:09 am
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| | Proceedings of the Symposium on the Mechanics of Growth and Remodeling in Native and Engineered Tissues. Marco Island, Florida, USA. June 25-29, 2008. J Biomech Eng. 2009 Oct;131(10):100201-4501 Authors: PMID: 20052790 [PubMed - indexed for MEDLINE] |
| Perfusion seeding of channeled elastomeric scaffolds with myocytes and endothelial cells for cardiac tissue engineering.
January 7, 2010 at 6:09 am
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| | Perfusion seeding of channeled elastomeric scaffolds with myocytes and endothelial cells for cardiac tissue engineering. Biotechnol Prog. 2010 Jan 5; Authors: Maidhof R, Marsano A, Lee EJ, Vunjak-Novakovic G The requirements for engineering clinically sized cardiac constructs include medium perfusion (to maintain cell viability throughout the construct volume) and the protection of cardiac myocytes from hydrodynamic shear. To reconcile these conflicting requirements, we proposed the use of porous elastomeric scaffolds with an array of channels providing conduits for medium perfusion, and sized to provide efficient transport of oxygen to the cells, by a combination of convective flow and molecular diffusion over short distances between the channels. In this study, we investigate the conditions for perfusion seeding of channeled constructs with myocytes and endothelial cells without the gel carrier we previously used to lock the cells within the scaffold pores. We first established the flow parameters for perfusion seeding of porous elastomer scaffolds using the C2C12 myoblast line, and determined that a linear perfusion velocity of 1.0 mm/s resulted in seeding efficiency of 87% +/- 26% within 2 hours. When applied to seeding of channeled scaffolds with neonatal rat cardiac myocytes, these conditions also resulted in high efficiency (77.2% +/- 23.7%) of cell seeding. Uniform spatial cell distributions were obtained when scaffolds were stacked on top of one another in perfusion cartridges, effectively closing off the channels during perfusion seeding. Perfusion seeding of single scaffolds resulted in preferential cell attachment at the channel surfaces, and was employed for seeding scaffolds with rat aortic endothelial cells. We thus propose that these techniques can be utilized to engineer thick and compact cardiac constructs with parallel channels lined with endothelial cells. (c) 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010. PMID: 20052737 [PubMed - as supplied by publisher] |
| IGF-1 and BMP-2 Induces Differentiation of Adipose-Derived Mesenchymal Stem Cells into Chondrocytes-Like Cells.
January 7, 2010 at 6:09 am
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| | IGF-1 and BMP-2 Induces Differentiation of Adipose-Derived Mesenchymal Stem Cells into Chondrocytes-Like Cells. Ann Biomed Eng. 2010 Jan 6; Authors: An C, Cheng Y, Yuan Q, Li J Articular cartilage defects are common, causing significant morbidities. Tissue engineering using pluripotent stem cells is a new promising modality for cartilage repair. In the current study, we investigated the chondrogenesis of rabbit adipose-derived stem cells (ADSCs). We isolated rabbit ADSCs and transfected these cells with constructs encoding human insulin growth like factor 1 (IGF-1) and bone morphogenic protein 2 (BMP-2). We examined the growth and morphology of these transfected cells and their production of type II collagen and MMP-3. We found that IGF-1 and BMP-2 drove the chondrogenesis of ADSCs, which showed mature chondrocyte-like cells and formed cartilage nodules. These cells also produced type II collagen with a reduced production of MMP-3. Our findings suggested that human ADSCs could differentiate into chondrocyte-like cells driven by IGF-1 and BMP-2 and held promises as an abundant and ready source of stem cells for cartilage repair and regeneration. PMID: 20052615 [PubMed - as supplied by publisher] |
| Kinetic studies of a composite carbon nanotube-hydrogel for tissue engineering by rheological methods.
January 7, 2010 at 6:09 am
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| | Kinetic studies of a composite carbon nanotube-hydrogel for tissue engineering by rheological methods. J Mater Sci Mater Med. 2010 Jan 6; Authors: Xie F, Weiss P, Chauvet O, Le Bideau J, Tassin JF Here we used rheological methods to study the gelation kinetics of silanized hydroxypropylmethylcellulose (HPMC-Si) hydrogel for tissue engineering. Firstly, the gelation time was determined from the independence of tan delta on frequency, and the Arrhenius law was applied to obtain the apparent activation energy of gelation, which was found to be about 109.0 kJ/mol. Secondly, the gelation process was monitored by measuring the sample storage modulus. The results showed that the gelation process could be well classified as a second-order reaction. In addition, a composite HPMC-Si/MWNTs hydrogel system for potential cartilage tissue engineering was investigated. The comparison of pure HPMC-Si hydrogel and composite HPMC-Si/MWNTs systems indicated that the addition of MWNTs could increase the mechanical strength of hydrogel without changing the gelation mechanism of the system. PMID: 20052519 [PubMed - as supplied by publisher] |
| Rotational maneuver of ferromagnetic nanowires for cell manipulation.
January 7, 2010 at 6:09 am
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| | Rotational maneuver of ferromagnetic nanowires for cell manipulation. IEEE Trans Nanobioscience. 2009 Sep;8(3):226-36 Authors: Zhao Y, Zeng H 1-D magnetic nanowires provide a powerful tool for investigating biological systems because such nanomaterials possess unique magnetic properties, which allow effective manipulation of cellular and subcellular objects. In this study, we report the rotational maneuver of ferromagnetic nanowires and their applications in cell manipulation. The rotational maneuver is studied under two different suspension conditions. The rotation of nanowires in the fluid is analyzed using Stokes flow assumption. Experimental results show that when the nanowires develop contacts with the bottom surfaces, the rotational maneuver under a modest external magnetic field can generate rapid lateral motion. The floating nanowires, on the other hand, do not exhibit substantial lateral displacements. Cell manipulation using skeletal myoblasts C2C12 shows that living cells can be manipulated efficiently on the bottom surface by the rotational maneuver of the attached nanowires. We also demonstrate the use of rotational maneuver of nanowires for creating 3-D nanowire clusters and multicellular clusters. This study is expected to add to the knowledge of nanowire-based cell manipulation and contribute to a full spectrum of control strategies for efficient use of nanowires for micro-total-analysis. It may also facilitate mechanobiological studies at cellular level, and provide useful insights for development of 3-D in vivo-like multicellular models for various applications in tissue engineering. PMID: 20051338 [PubMed - in process] |
| The potential of stem cells in the treatment of knee cartilage defects.
January 7, 2010 at 6:09 am
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| | The potential of stem cells in the treatment of knee cartilage defects. Knee. 2010 Jan 3; Authors: Khan WS, Johnson DS, Hardingham TE Cartilage is frequently damaged but only shows a limited capacity for repair. There are a number of treatment strategies currently available for the repair of articular cartilage defects including abrasion chondroplasty, subchondral drilling, microfracture and mosaicplasty but these show variable results. For the younger patients, there is great interest in the potential of cell-based strategies to provide a biological replacement of damaged cartilage using autologous chondrocytes. The results of clinical studies using these cell-based techniques do not conclusively show improvement over conventional techniques. These techniques also do not consistently result in the formation of the desired hyaline cartilage rather than fibrocartilage. Mesenchymal stem cells present a promising cell source for cartilage repair. Mesenchymal stem cells have been isolated from a number of adult tissues including the bone marrow and the synovial fat pad. These cells have the ability to proliferate in culture and differentiate down different pathways including the chondrogenic pathway. In the first instance, differentiated stem cells can be used for the repair of localised cartilage defects by producing hyaline cartilage. In the future, this strategy has the potential to be extended to treat more generalised cartilage defects, especially as the cell source is not a limiting factor. The use of cell-based therapies also allows the versatility of using scaffolds and growth factors, with recombinant proteins or gene therapy. A number of challenges however still need to be overcome including further work on identifying the optimal source of stem cells, along with refining the conditions that enhance expansion and chondrogenesis. PMID: 20051319 [PubMed - as supplied by publisher] |
| A Facile Method to Fabricate Poly(L-lactide) Nano-fibrous Morphologies by Phase Inversion.
January 7, 2010 at 6:09 am
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| | A Facile Method to Fabricate Poly(L-lactide) Nano-fibrous Morphologies by Phase Inversion. Acta Biomater. 2010 Jan 2; Authors: Papenburg BJ, Bolhuis-Versteeg LA, Grijpma DW, Feijen J, Wessling M, Stamatialis D Scaffolds with a nano-fibrous morphology are favored in certain tissue engineering applications as this morphology mimics the tissue's natural extracellular matrix secreted by the cells, which consists of mainly collagen fibers with diameters ranging from 50-400 nm. Porous poly(L-lactide) (PLLA) scaffolds obtained by phase inversion methods generally have a solid-wall pore morphology. In contrast, this work presents a facile method to fabricate highly porous and highly interconnected nano-fibrous scaffold sheets by phase inversion using PLLA of very high molecular weight (5.7x10(5) g/mol). The scaffold sheets consist of nano-fibers within the desired range of 50-500 nm. When applying phase separation micromolding (PSmuM) as fabrication method besides the porous nano-fibrous morphology an additional topography can be introduced into these sheets,. Culturing of C2C12 pre-myoblasts on these nano-fibrous sheets reveals very good cell adhesion, morphology and proliferation. Excellent alignment of the cells is induced by fabrication of 25 mum wide microchannels in these sheets. These results warrant further evaluation of these sheets as tissue engineering scaffolds. PMID: 20051272 [PubMed - as supplied by publisher] |
| Cell interactions in bone tissue engineering.
January 7, 2010 at 6:09 am
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| | Cell interactions in bone tissue engineering. J Cell Mol Med. 2009 Dec 27; Authors: Pirraco RP, Marques AP, Reis RL Abstract Bone fractures where the innate regenerative bone response is compromised represent between 4 and 8 hundred thousand of the total fracture cases, just in the US. Bone Tissue Engineering (TE) brought the notion that, in cases such as those, it was preferable to boost the healing process of bone tissue instead of just adding artificial parts that could never properly replace the native tissue. However, despite the hype, Bone TE so far could not live up to its promises and new bottom-up approaches are needed. The study of the cellular interactions between the cells relevant for bone biology can be of essential importance to that. In living bone, cells are in a context where communication with adjacent cells is almost permanent. Many fundamental works have been addressing these communications nonetheless, in a bone TE approach, the 3D perspective, being part of the microenvironment of a bone cell, is as crucial. Works combining the study of cell to cell interactions in a 3D environment are not as many as expected. Therefore, the bone TE field should not only gain knowledge from the field of fundamental Biology but also contribute for further understanding the biology of bone. In this review, a summary of the main works in the field of bone TE, aiming at studying cellular interactions in a 3D environment, and how they contributed towards the development of a functional engineered bone tissue, is presented. PMID: 20050963 [PubMed - as supplied by publisher] |
| Proteomic characterization of mesenchymal stem cell-like populations derived from ovine periodontal ligament, dental pulp and bone marrow: analysis of differentially expressed proteins.
January 7, 2010 at 6:09 am
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| | Proteomic characterization of mesenchymal stem cell-like populations derived from ovine periodontal ligament, dental pulp and bone marrow: analysis of differentially expressed proteins. Stem Cells Dev. 2010 Jan 5; Authors: Mrozik KM, Zilm PS, Bagley C, Hack S, Hoffmann P, Gronthos S, Bartold PM Post-natal mesenchymal stem/stromal-like cells (MSCs) including periodontal ligament stem cells (PDLSCs), dental pulp stem cells (DPSCs) and bone marrow stromal cells (BMSCs) are capable of self-renewal and differentiation into multiple mesenchymal cell lineages. Despite their similar expression of MSC-associated and osteoblastic markers, MSCs retain the capacity to generate structures resembling the microenvironments from which they are derived in vivo and represent a promising therapy for the regeneration of complex tissues in the clinical setting. With this in mind, systematic approaches are required to identify the differential protein expression patterns responsible for lineage commitment and mediating the formation of these complex structures. This is the first study to compare the differential proteomic expression profiles of ex vivo-expanded ovine PDLSCs, DPSCs and BMSCs derived from an individual donor. Two-dimensional electrophoresis was performed and regulated proteins were identified by Liquid chromatography -- Electrospray-Ionisation tandem mass spectrometry (MS & MS/MS), database searching and de novo sequencing. In total, 58 proteins were differentially expressed between at least two MSC populations in both sheep, 12 of which were up-regulated in one MSC population relative to the other two. In addition, the regulation of selected proteins was also conserved between equivalent human MSC populations. We anticipate that differential protein expression profiling will provide a basis for elucidating the protein expression patterns and molecular cues that are crucial in specifying the characteristic growth and developmental capacity of dental and non-dental tissue-derived MSC populations. These expression patterns can serve as important tools for the regeneration of particular tissues in future stem cell-based tissue engineering studies using animal models. PMID: 20050811 [PubMed - as supplied by publisher] |
| Microcapsules embedded with 3D fibrous scaffolds for cell culture and tissue engineering.
January 7, 2010 at 6:09 am
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| | Microcapsules embedded with 3D fibrous scaffolds for cell culture and tissue engineering. Tissue Eng Part C Methods. 2010 Jan 5; Authors: Huang X, Wang J, Xie H, Zhang Y, Wang W, Yu W, Liu Y, Ma X Aggregating into multicellular spheroids (MCS) within alginate-poly-L-lysine-alginate (APA) microcapsules is important in maintaining the cellular viability and specific functions. However, in the absence of a vascular network, cells in the core of large-size spheroid are gradually necrotic due to oxygen transfer limitations. In this study, a novel APA microcapsule embedded with three dimensional fibrous scaffolds (called APA-FS) was proposed to eliminate cellular necrosis by regulating cells to form multi-small-spheroids. HepG2 cells were embedded within the APA-FS to form spheroids and the state of these spheroids was evaluated via MTT assay, Glucose/Lactate metabolism, Live/Dead staining and HE staining. Comparing with the conventional APA microcapsules, the cells within APA-FS organized into multi-small-spheroids. The size of these spheroids depended on the concentration of fibrous scaffolds embedded within the microcapsules. In the APA-FS embedded with 5% v/v fibrous scaffolds, the average size of cellular spheroids was controlled below 100 microm and the cellular viability was increased by 50% than the control. The results of Live/Dead staining and HE staining showed that the improved cellular viability might be attributed to the decreased necrosis in the core of these spheroids. The improved viability of cells demonstrated the efficiency of this technology. These findings implied that this system might provide a more suitable culture environment for a variety of tissue engineering applications. PMID: 20050807 [PubMed - as supplied by publisher] |
| System and method for investigating arterial remodeling.
January 7, 2010 at 6:09 am
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| | System and method for investigating arterial remodeling. J Biomech Eng. 2009 Oct;131(10):104501 Authors: Rachev A, Dominguez Z, Vito R Organ culture systems are used to study remodeling of arteries and to fabricate tissue engineered vascular grafts. Investigations to date focused on changes in geometry and mechanical response of arteries or constructs associated with controlled sustained alterations in the global load parameters such as the arterial pressure, flow, or axial stretch. A new experimental paradigm is proposed, which is based on the simultaneous independent control of local mechanical parameters such as mean strain or stress in the arterial wall and flow-induced shear at the intima. An organ culture system and methodology were developed, which controls pressure, flow, and axial length of a specimen in order to maintain the local mechanical parameters at prescribed values. The operation of the system is illustrated by maintenance of elevated axial medial stress in porcine carotid artery, while keeping the mean circumferential stress and flow-induced shear stress at baseline values. Previously unknown aspects of remodeling that might be revealed by the novel approach are discussed. PMID: 19831489 [PubMed - indexed for MEDLINE] |
| Morphological and functional characteristics of three-dimensional engineered bone-ligament-bone constructs following implantation.
January 7, 2010 at 6:09 am
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| | Morphological and functional characteristics of three-dimensional engineered bone-ligament-bone constructs following implantation. J Biomech Eng. 2009 Oct;131(10):101017 Authors: Ma J, Goble K, Smietana M, Kostrominova T, Larkin L, Arruda EM The incidence of ligament injury has recently been estimated at 400,000/year. The preferred treatment is reconstruction using an allograft, but outcomes are limited by donor availability, biomechanical incompatibility, and immune rejection. The creation of an engineered ligament in vitro solely from patient bone marrow stromal cells (has the potential to greatly enhance outcomes in knee reconstructions. Our laboratory has developed a scaffoldless method to engineer three-dimensional (3D) ligament and bone constructs from rat bone marrow stem cells in vitro. Coculture of these two engineered constructs results in a 3D bone-ligament-bone (BLB) construct with viable entheses, which was successfully used for medial collateral ligament (MCL) replacement in a rat model. 1 month and 2 month implantations were applied to the engineered BLBs. Implantation of 3D BLBs in a MCL replacement application demonstrated that our in vitro engineered tissues grew and remodeled quickly in vivo to an advanced phenotype and partially restored function of the knee. The explanted 3D BLB ligament region stained positively for type I collagen and elastin and was well vascularized after 1 and 2 months in vivo. Tangent moduli of the ligament portion of the 3D BLB 1 month explants increased by a factor of 2.4 over in vitro controls, to a value equivalent to those observed in 14-day-old neonatal rat MCLs. The 3D BLB 1 month explants also exhibited a functionally graded response that closely matched native MCL inhomogeneity, indicating the constructs functionally adapted in vivo. PMID: 19831487 [PubMed - indexed for MEDLINE] |
| A phenomenological model for mechanically mediated growth, remodeling, damage, and plasticity of gel-derived tissue engineered blood vessels.
January 7, 2010 at 6:09 am
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| | A phenomenological model for mechanically mediated growth, remodeling, damage, and plasticity of gel-derived tissue engineered blood vessels. J Biomech Eng. 2009 Oct;131(10):101016 Authors: Raykin J, Rachev AI, Gleason RL Mechanical stimulation has been shown to dramatically improve mechanical and functional properties of gel-derived tissue engineered blood vessels (TEBVs). Adjusting factors such as cell source, type of extracellular matrix, cross-linking, magnitude, frequency, and time course of mechanical stimuli (among many other factors) make interpretation of experimental results challenging. Interpretation of data from such multifactor experiments requires modeling. We present a modeling framework and simulations for mechanically mediated growth, remodeling, plasticity, and damage of gel-derived TEBVs that merge ideas from classical plasticity, volumetric growth, and continuum damage mechanics. Our results are compared with published data and suggest that this model framework can predict the evolution of geometry and material behavior under common experimental loading scenarios. PMID: 19831486 [PubMed - indexed for MEDLINE] |
| Fabrication and modeling of dynamic multipolymer nanofibrous scaffolds.
January 7, 2010 at 6:09 am
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| | Fabrication and modeling of dynamic multipolymer nanofibrous scaffolds. J Biomech Eng. 2009 Oct;131(10):101012 Authors: Baker BM, Nerurkar NL, Burdick JA, Elliott DM, Mauck RL Aligned nanofibrous scaffolds hold tremendous potential for the engineering of dense connective tissues. These biomimetic micropatterns direct organized cell-mediated matrix deposition and can be tuned to possess nonlinear and anisotropic mechanical properties. For these scaffolds to function in vivo, however, they must either recapitulate the full dynamic mechanical range of the native tissue upon implantation or must foster cell infiltration and matrix deposition so as to enable construct maturation to meet these criteria. In our recent studies, we noted that cell infiltration into dense aligned structures is limited but could be expedited via the inclusion of a distinct rapidly eroding sacrificial component. In the present study, we sought to further the fabrication of dynamic nanofibrous constructs by combining multiple-fiber populations, each with distinct mechanical characteristics, into a single composite nanofibrous scaffold. Toward this goal, we developed a novel method for the generation of aligned electrospun composites containing rapidly eroding (PEO), moderately degradable (PLGA and PCL/PLGA), and slowly degrading (PCL) fiber populations. We evaluated the mechanical properties of these composites upon formation and with degradation in a physiologic environment. Furthermore, we employed a hyperelastic constrained-mixture model to capture the nonlinear and time-dependent properties of these scaffolds when formed as single-fiber populations or in multipolymer composites. After validating this model, we demonstrated that by carefully selecting fiber populations with differing mechanical properties and altering the relative fraction of each, a wide range of mechanical properties (and degradation characteristics) can be achieved. This advance allows for the rational design of nanofibrous scaffolds to match native tissue properties and will significantly enhance our ability to fabricate replacements for load-bearing tissues of the musculoskeletal system. PMID: 19831482 [PubMed - indexed for MEDLINE] | | | 
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