共查询到20条相似文献,搜索用时 15 毫秒
1.
Benjamin?L. Vaughan Jr. Peter?A. Galie Jan?P. Stegemann James?B. Grotberg 《Biophysical journal》2013,105(9):2188-2198
In the creation of engineered tissue constructs, the successful transport of nutrients and oxygen to the contained cells is a significant challenge. In highly porous scaffolds subject to cyclic strain, the mechanical deformations can induce substantial fluid pressure gradients, which affect the transport of solutes. In this article, we describe a poroelastic model to predict the solid and fluid mechanics of a highly porous hydrogel subject to cyclic strain. The model was validated by matching the predicted penetration of a bead into the hydrogel from the model with experimental observations and provides insight into nutrient transport. Additionally, the model provides estimates of the wall-shear stresses experienced by the cells embedded within the scaffold. These results provide insight into the mechanics of and convective nutrient transport within a cyclically strained hydrogel, which could lead to the improved design of engineered tissues. 相似文献
2.
Mechanically induced cell deformations have been shown to influence chondrocyte response in 3D culture. However, the relationship between the mechanical stimulation and cell response is not yet fully understood. In this study a finite element model was developed to investigate cell-matrix interactions under unconfined compression conditions, using a tissue engineered encapsulating hydrogel seeded with chondrocytes. Model predictions of stress and strain distributions within the cell and on the cell boundary were shown to exhibit space-dependent responses that varied with scaffold mechanical properties, the presence of a pericellular matrix (PCM), and the cell size. The simulations predicted that when the cells were initially encapsulated into the hydrogel scaffolds, the cell size hardly affected the magnitude of the stresses and strains that were reaching the encapsulated cells. However, with the inclusion of a PCM layer, larger cells experienced enhanced stresses and strains resulting from the mechanical stimulation. It was also noted that the PCM had a stress shielding effect on the cells in that the peak stresses experienced within the cells during loading were significantly reduced. On the other hand, the PCM caused the stresses at the cell-matrix interface to increase. Based on the model predictions, the PCM modified the spatial stress distribution within and around the encapsulated cells by redirecting the maximum stresses from the periphery of the cells to the cell nucleus. In a tissue engineered cartilage exposed to mechanical loading, the formation of a neo-PCM by encapsulated chondrocytes appears to protect them from initially excessive mechanical loading. Predictive models can thus shed important insight into how chondrocytes remodel their local environment in order to redistribute mechanical signals in tissue engineered constructs. 相似文献
3.
G. Sciumè S.E. Shelton W.G. Gray C.T. Miller F. Hussain M. Ferrari P. Decuzzi B.A. Schrefler 《Molecular & cellular biomechanics : MCB》2012,9(3):193-212
Multiphase porous media mechanics is used for modeling tumor growth, using governing equations obtained via the Thermodynamically Constrained Averaging Theory (TCAT). This approach incorporates the interaction of more phases than legacy tumor growth models. The tumor is treated as a multiphase system composed of an extracellular matrix, tumor cells which may become necrotic depending on nutrient level and pressure, healthy cells and an interstitial fluid which transports nutrients. The governing equations are numerically solved within a Finite Element framework for predicting the growth rate of the tumor mass, and of its individual components, as a function of the initial tumor-to-healthy cell ratio, nutrient concentration, and mechanical strain. Preliminary results are shown. 相似文献
4.
Decellularization and cellularization of organs have emerged as disruptive methods in tissue engineering and regenerative medicine. Porous hydrogel scaffolds have widespread applications in tissue engineering, regenerative medicine and drug discovery as viable tissue mimics. However, the existing hydrogel fabrication techniques suffer from limited control over pore interconnectivity, density and size, which leads to inefficient nutrient and oxygen transport to cells embedded in the scaffolds. Here, we demonstrated an innovative approach to develop a new platform for tissue engineered constructs using live bacteria as sacrificial porogens. E.coli were patterned and cultured in an interconnected three-dimensional (3D) hydrogel network. The growing bacteria created interconnected micropores and microchannels. Then, the scafold was decellularized, and bacteria were eliminated from the scaffold through lysing and washing steps. This 3D porous network method combined with bioprinting has the potential to be broadly applicable and compatible with tissue specific applications allowing seeding of stem cells and other cell types. 相似文献
5.
Intervertebral disc metabolic transport is essential to the functional spine and provides the cells with the nutrients necessary to tissue maintenance. Disc degenerative changes alter the tissue mechanics, but interactions between mechanical loading and disc transport are still an open issue. A poromechanical finite element model of the human disc was coupled with oxygen and lactate transport models. Deformations and fluid flow were linked to transport predictions by including strain-dependent diffusion and advection. The two solute transport models were also coupled to account for cell metabolism. With this approach, the relevance of metabolic and mechano-transport couplings were assessed in the healthy disc under loading-recovery daily compression. Disc height, cell density and material degenerative changes were parametrically simulated to study their influence on the calculated solute concentrations. The effects of load frequency and amplitude were also studied in the healthy disc by considering short periods of cyclic compression. Results indicate that external loads influence the oxygen and lactate regional distributions within the disc when large volume changes modify diffusion distances and diffusivities, especially when healthy disc properties are simulated. Advection was negligible under both sustained and cyclic compression. Simulating degeneration, mechanical changes inhibited the mechanical effect on transport while disc height, fluid content, nucleus pressure and overall cell density reductions affected significantly transport predictions. For the healthy disc, nutrient concentration patterns depended mostly on the time of sustained compression and recovery. The relevant effect of cell density on the metabolic transport indicates the disturbance of cell number as a possible onset for disc degeneration via alteration of the metabolic balance. Results also suggest that healthy disc properties have a positive effect of loading on metabolic transport. Such relation, relevant to the maintenance of the tissue functional composition, would therefore link disc function with disc nutrition. 相似文献
6.
Reduction of porous media permeability from in situ Leuconostoc mesenteroides growth and dextran production 总被引:1,自引:0,他引:1
In situ growth of bacteria in a porous medium can alter the permeability of that media. This article reveals that the rate of permeability alteration can be controlled by the inoculation strategy, nutrient concentrations, and injection rates. Based on experimental observations a phenomenological model has been developed to describe the inoculation of the porous medium, the in situ growth of bacteria, and the permeability decline of the porous medium. This model consists of two phases that describe the bacteria in the porous medium: (1) the nongrowth phase in which cell transport and retention are occurring; and (2) the growth phase in which the retained cells grow and plug the porous media. Transition from the transport phase to the growth phase is governed by the growth lag time of the cells within the porous medium. The importance of the inoculum injection strategy and the nutrient injection strategy is illustrated by the model. (c) 1996 John Wiley & Sons, Inc. 相似文献
7.
Narayanan H Arruda EM Grosh K Garikipati K 《Biomechanics and modeling in mechanobiology》2009,8(3):167-181
In this paper, we address some modelling issues related to biological growth. Our treatment is based on a formulation for
growth that was proposed within the context of mixture theory (J Mech Phys Solids 52:1595–1625, 2004). We aim to make this
treatment more appropriate for the physics of porous soft tissues, paying particular attention to the nature of fluid transport,
and mechanics of fluid and solid phases. The interactions between transport and mechanics have significant implications for
growth and swelling. We also reformulate the governing differential equations for reaction-transport of solutes to represent
the incompressibility constraint on the fluid phase of the tissue. This revision enables a straightforward implementation
of numerical stabilisation for the advection-dominated limit of these equations. A finite element implementation with operator
splitting is used to solve the coupled, non-linear partial differential equations that arise from the theory. We carry out
a numerical and analytic study of the convergence of the operator splitting scheme subject to strain- and stress-homogenisation
of the mechanics of fluid–solid interactions. A few computations are presented to demonstrate aspects of the physical mechanisms,
and the numerical performance of the formulation. 相似文献
8.
Selection of Bacteria with Favorable Transport Properties Through Porous Rock for the Application of Microbial-Enhanced Oil Recovery 总被引:6,自引:6,他引:0
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Long-Kuan Jang Philip W. Chang John E. Findley Teh Fu Yen 《Applied microbiology》1983,46(5):1066-1072
This paper presents a bench-scale study on the transport in highly permeable porous rock of three bacterial species—Bacillus subtilis, Pseudomonas putida, and Clostridium acetobutylicum—potentially applicable in microbial-enhanced oil recovery processes. The transport of cells during the injection of bacterial suspension and nutrient medium was simulated by a deep bed filtration model. Deep bed filtration coefficients and the maximum capacity of cells in porous rock were measured. Low to intermediate (~106/ml) injection concentrations of cellular suspensions are recommended because plugging of inlet surface is less likely to occur. In addition to their resistance to adverse environments, spores of clostridia are strongly recommended for use in microbial-enhanced oil recovery processes since they are easiest among the species tested to push through porous rock. After injection, further transport of bacteria during incubation can occur by growth and mobility through the stagnant nutrient medium which fills the porous rock. We have developed an apparatus to study the migration of bacteria through a Berea sandstone core containing nutrient medium. 相似文献
9.
A thermosensitive hydrogel capable of differentiating mesenchymal stem cells (MSCs) into cardiomyocyte-like cells was synthesized. The hydrogel was based on N-isopropylacrylamide (NIPAAm), N-acryloxysuccinimide, acrylic acid, and hydroxyethyl methacrylate-poly(trimethylene carbonate). The hydrogel was highly flexible at body temperature with breaking strain >1000% and Young's modulus 45 kPa. When MSCs were encapsulated in the hydrogel and cultured under normal culture conditions (10% FBS and 21% O(2)), the cells differentiated into cardiomyocyte-like cells. However, the differentiation was retarded, and even diminished, under low nutrient and low oxygen conditions, which are typical of the infarcted heart. We hypothesized that enhancing MSC survival under low nutrient and low oxygen conditions would restore the differentiation. To enhance cell survival, a pro-survival growth factor (bFGF) was loaded in the hydrogel. bFGF was able to sustainedly release from the hydrogel for 21 days. Under the low nutrient and low oxygen conditions (1% O(2) and 1% FBS), bFGF enhanced MSC survival and differentiation in the hydrogel. After 14 days of culture, survival of 70.5% of MSCs remained in the bFGF-loaded hydrogel, while only 4.9% of MSCs remained in the hydrogel without bFGF. The differentiation toward cardiomyocyte-like cells was completely inhibited at 1% FBS and 1% oxygen. Loading bFGF in the hydrogel restored the differentiation, as confirmed by the expression of cardiac markers at both the gene (MEF2C and CACNA1c) and protein (cTnI and connexin 43) levels. bFGF loading also up-regulated the paracrine effect of MSCs. VEGF expression was significantly increased in the bFGF-loaded hydrogel. These results demonstrate that the developed bFGF-loaded hydrogel may potentially be used to deliver MSCs into hearts for regeneration of heart tissue. 相似文献
10.
Unraveling the organization of the FG repeat meshwork that forms the active transport channel of the nuclear pore complex (NPC) is key to understanding the mechanism of nucleocytoplasmic transport. In this paper, we develop a tool to probe the FG repeat network in living cells by modifying FG nucleoporins (Nups) with a binding motif (engineered dynein light chain-interacting domain) that can drag several copies of an interfering protein, Dyn2, into the FG network to plug the pore and stop nucleocytoplasmic transport. Our method allows us to specifically probe FG Nups in vivo, which provides insight into the organization and function of the NPC transport channel. 相似文献
11.
Julia J. Mack Abigail A. Corrin Sergio L. dos Santos e Lucato James C.Y. Dunn Benjamin W. Wu Brian N. Cox 《Biotechnology and bioengineering》2013,110(3):936-946
A novel magnetically actuated scaffold was used to explore the effects of strain stimulus on the proliferation and spatial distribution of smooth muscle cells and improve cell viability in the scaffold interior by pumping nutrients throughout the structure. Magnetically actuable scaffolds were fabricated in a tube shape by winding electrospun sheets of a biodegradable polymer modified with magnetic Fe2O3 nanoparticles. Prior to rolling, the sheets were seeded with smooth muscle cells and wound into tubes with diameter 5.2 mm and wall thickness 0.2 mm. The tubular scaffolds were actuated by a magnetic field to induce a cyclic crimping deformation, which applies strain stimulus to the cells and pumps nutrient fluid through the porous tube walls. Comparison with non‐actuated controls shows that magnetic actuation increases the total cell count throughout the scaffold after 14 days of incubation. Furthermore, whereas cell density as a function of position through the tube wall thickness showed a minimum in the mid‐interior in the controls after 14 days due to cell starvation, the actuated scaffolds displayed a maximum cell density. Comparison of cell distributions with the expected spatial variations in strain amplitude and nutrient flux implies that both strain stimulus and nutrient pumping are significant factors in cell proliferation. Biotechnol. Bioeng. 2013; 110: 936–946. © 2012 Wiley Periodicals, Inc. 相似文献
12.
Human adipose-derived stem cells (hASC) exhibit multilineage differentiation potential with lineage specification that is dictated by both the chemical and mechanical stimuli to which they are exposed. We have previously shown that 10% cyclic tensile strain increases hASC osteogenesis and cell-mediated calcium accretion. We have also recently shown that primary cilia are present on hASC and that chemically-induced lineage specification of hASC concurrently results in length and conformation changes of the primary cilia. Further, we have observed cilia length changes in hASC cultured within a collagen I gel in response to 10% cyclic tensile strain. We therefore hypothesize that primary cilia may play a key mechanotransduction role for hASC exposed to tensile strain. The goal of this study was to use finite element analysis (FEA) to determine strains occurring within the ciliary membrane in response to 10% tensile strain applied parallel, or perpendicular, to cilia orientation. To elucidate the mechanical environment experienced by the cilium, several lengths were modeled and evaluated based on cilia lengths measured on hASC grown under varied culture conditions. Principal tensile strains in both hASC and ciliary membranes were calculated using FEA, and the magnitude and location of maximum principal tensile strain determined. We found that maximum principal tensile strain was concentrated at the base of the cilium. In the linear elastic model, applying strain perpendicular to the cilium resulted in maximum strains within the ciliary membrane from 150% to 200%, while applying strain parallel to the cilium resulted in much higher strains, approximately 400%. In the hyperelastic model, applying strain perpendicular to the cilium resulted in maximum strains within the ciliary membrane around 30%, while applying strain parallel to the cilium resulted in much higher strains ranging from 50% to 70%. Interestingly, FEA results indicated that primary cilium length was not directly related to ciliary membrane strain. Rather, it appears that cilium orientation may be more important than cilium length in determining sensitivity of hASC to tensile strain. This is the first study to model the effects of tensile strain on the primary cilium and provides newfound insight into the potential role of the primary cilium as a mechanosensor, particularly in tensile strain and potentially a multitude of other mechanical stimuli beyond fluid shear. 相似文献
13.
Christopher A Vaiana Hyungseok Kim Jonathan Cottet Keiko Oai Zhifei Ge Kameron Conforti Andrew M King Adam J Meyer Haorong Chen Christopher A Voigt Cullen R Buie 《Molecular systems biology》2022,18(3)
Living materials combine a material scaffold, that is often porous, with engineered cells that perform sensing, computing, and biosynthetic tasks. Designing such systems is difficult because little is known regarding signaling transport parameters in the material. Here, the development of a porous microplate is presented. Hydrogel barriers between wells have a porosity of 60% and a tortuosity factor of 1.6, allowing molecular diffusion between wells. The permeability of dyes, antibiotics, inducers, and quorum signals between wells were characterized. A “sentinel” strain was constructed by introducing orthogonal sensors into the genome of Escherichia coli MG1655 for IPTG, anhydrotetracycline, L‐arabinose, and four quorum signals. The strain’s response to inducer diffusion through the wells was quantified up to 14 mm, and quorum and antibacterial signaling were measured over 16 h. Signaling distance is dictated by hydrogel adsorption, quantified using a linear finite element model that yields adsorption coefficients from 0 to 0.1 mol m−3. Parameters derived herein will aid the design of living materials for pathogen remediation, computation, and self‐organizing biofilms. 相似文献
14.
Extensive experimental work on the effects of penetrating annular injuries indicated that large injuries impact axial compressive properties of small animal intervertebral discs, yet there is some disagreement regarding the sensitivity of mechanical tests to small injury sizes. In order to understand the mechanism of injury size sensitivity, this study proposed a simple one dimensional model coupling elastic deformations in the annulus with fluid flow into and out of the nucleus through both porous boundaries and through a penetrating annular injury. The model was evaluated numerically in dynamic compression with parameters obtained by fitting the solution to experimental stress-relaxation data. The model predicted low sensitivity of mechanical changes to injury diameter at both small and large sizes (as measured by low and high ratios of injury diameter to annulus thickness), with a narrow range of high sensitivity in between. The size at which axial mechanics were most sensitive to injury size (i.e., critical injury size) increased with loading frequency. This study provides a quantitative hypothetical model of how penetrating annulus fibrosus injuries in discs with a gelatinous nucleus pulposus may alter disc mechanics by changing nucleus pulposus fluid pressurization through introduction of a new fluid transport pathway though the annulus. This model also explains how puncture-induced biomechanical changes depend on both injury size and test protocol. 相似文献
15.
Perfusion bioreactors improve mass transfer in cell-scaffold constructs. We developed a mathematical model to simulate nutrient flow through cellular constructs. Interactions among cell proliferation, nutrient consumption, and culture medium circulation were investigated. The model incorporated modified Contois cell-growth kinetics that includes effects of nutrient saturation and limited cell growth. Nutrient uptake was depicted through the Michaelis-Menton kinetics. To describe the culture medium convection, the fluid flow outside the cell-scaffold construct was described by the Navier-Stokes equations, while the fluid dynamics within the construct was modeled by Brinkman's equation for porous media flow. Effects of the media perfusion were examined by including time-dependant porosity and permeability changes due to cell growth. The overall cell volume was considered to consist of cells and extracellular matrices (ECM) as a whole without treating ECM separately. Numerical simulations show when cells were cultured subjected to direct perfusion, they penetrated to a greater extent into the scaffold and resulted in a more uniform spatial distribution. The cell amount was increased by perfusion and ultimately approached an asymptotic value as the perfusion rates increased in terms of the dimensionless Peclet number that accounts for the ratio of nutrient perfusion to diffusion. In addition to enhancing the nutrient delivery, perfusion simultaneously imposes flow-mediated shear stress to the engineered cells. Shear stresses were found to increase with cell growth as the scaffold void space was occupied by the cell and ECM volumes. The macro average stresses increased from 0.2 mPa to 1 mPa at a perfusion rate of 20 microm/s with the overall cell volume fraction growing from 0.4 to 0.7, which made the overall permeability value decrease from 1.35 x 10(-2)cm(2) to 5.51 x 10(-4)cm(2). Relating the simulation results with perfusion experiments in literature, the average shear stresses were below the critical value that would induce the chondrocyte necrosis. 相似文献
16.
Vittorio Sansalone Joanna Kaiser Salah Naili Thibault Lemaire 《Biomechanics and modeling in mechanobiology》2013,12(3):533-553
Canalicular fluid flow is acknowledged to play a major role in bone functioning, allowing bone cells’ metabolism and activity and providing an efficient way for cell-to-cell communication. Bone canaliculi are small canals running through the bone solid matrix, hosting osteocyte’s dendrites, and saturated by an interstitial fluid rich in ions. Because of the small size of these canals (few hundred nanometers in diameter), fluid flow is coupled with electrochemical phenomena. In our previous works, we developed a multi-scale model accounting for coupled hydraulic and chemical transport in the canalicular network. Unfortunately, most of the physical and geometrical information required by the model is hardly accessible by nowadays experimental techniques. The goal of this study was to numerically assess the influence of the physical and material parameters involved in the canalicular fluid flow. The focus was set on the electro-chemo-mechanical features of the canalicular milieu, hopefully covering any in vivo scenario. Two main results were obtained. First, the most relevant parameters affecting the canalicular fluid flow were identified and their effects quantified. Second, these findings were given a larger scope to cover also scenarios not considered in this study. Therefore, this study gives insight into the potential interactions between electrochemistry and mechanics in bone and provides the rational for further theoretical and experimental investigations. 相似文献
17.
A finite element analysis for the prediction of load-induced fluid flow and mechanochemical transduction in bone 总被引:6,自引:0,他引:6
Interstitial fluid flow through the lacunocanalicular cavities of mechanically loaded bone provides the biophysical basis for a number of postulates regarding mechanotransduction in bone. Recently, the existence of load-induced fluid flow and its influence on molecular transport through bone has been confirmed using tracer methods to visualize fluid flow induced by in vivo four-point-bending of rat tibiae. In this paper, we present a theoretical two-stage approach for the calculation of load-induced flow fields and for the evaluation of their influence on molecular transport in bone loaded in four-point bending, analogous to the aforementioned experimental model. In the first stage, the fluid velocities are calculated using a three-dimensional, poroelastic finite element model. In the second stage, mass transport analysis, this calculated fluid flow serves as a forced convection flow and its contribution to the total transport potential is determined. Based on this combined approach, the overall tracer concentration in the loaded bone is significantly higher than that in the unloaded bone. Furthermore, augmentation of mass transport through convective flow is more pronounced in the tension band of the tissue, as compared to the compression band. In general, augmentation of tracer concentration via convective mechanisms is most pronounced in areas corresponding to lowest fluid velocities, which is indicative of fluid flow direction and areas of increased "dwell time" or accumulation during the loading cycle. This theoretical model, in combination with the corresponding experimental model, provides unique insight into the role of mechanical loads in modulating local flow distributions and concentration gradients within bone tissue. 相似文献
18.
Chen T Buckley M Cohen I Bonassar L Awad HA 《Biomechanics and modeling in mechanobiology》2012,11(5):689-702
Interstitial flow in articular cartilage is secondary to compressive and shear deformations during joint motion and has been
linked with the well-characterized heterogeneity in structure and composition of its extracellular matrix. In this study,
we investigated the effects of introducing gradients of interstitial flow on the evolution of compositional heterogeneity
in engineered cartilage. Using a parallel-plate bioreactor, we observed that Poiseuille flow stimulation of chondrocyte-seeded
agarose hydrogels led to an increase in glycosaminoglycan and type II collagen deposition in the surface region of the hydrogel
exposed to flow. Experimental measurements of the interstitial flow fields based on the fluorescence recovery after photobleaching
technique suggested that the observed heterogeneity in composition is associated with gradients in interstitial flow in a
boundary layer at the hydrogel surface. Interestingly, the interstitial flow velocity profiles were nonlinearly influenced
by flow rate, which upon closer examination led us to the original observation that the apparent hydrogel permeability decreased
exponentially with increased interfacial shear stress. We also observed that interstitial flow enhances convective mass transport
irrespective of molecular size within the boundary layer near the hydrogel surface and that the convective contribution to
transport diminishes with depth in association with interstitial flow gradients. The implications of the nonlinearly inverse
relationship between the interfacial shear stress and the interstitial flux and permeability and its consequences for convective
transport are important for tissue engineering, since porous scaffolds comprise networks of Poiseuille channels (pores) through
which interstitial flow must navigate under mechanical stimulation or direct perfusion. 相似文献
19.
Daphne van Geemen Anita Driessen-Mol Frank P. T. Baaijens Carlijn V. C. Bouten 《Cell and tissue research》2013,352(3):727-737
Mechanical conditioning is often used to enhance collagen synthesis, remodeling and maturation and, hence, the structural and mechanical properties of engineered cardiovascular tissues. Intermittent straining, i.e., alternating periods of cyclic and static strain, has previously been shown to result in more mature tissue compared with continuous cyclic straining. Nevertheless, the underlying mechanism is unknown. We have determined the short-term effects of continuous cyclic strain and of cyclic strain followed by static strain at the gene expression level to improve insight into the mechano-regulatory mechanism of intermittent conditioning on collagen synthesis, remodeling and maturation. Tissue-engineered constructs, consisting of human vascular-derived cells seeded onto rapidly degrading PGA/P4HB scaffolds, were conditioned with 4% strain at 1 Hz for 3 h in order to study the immediate effects of cyclic strain (n=18). Next, the constructs were either subjected to ongoing cyclic strain (4% at 1 Hz; n=9) or to static strain (n=9). Expression levels of genes involved in collagen synthesis, remodeling and maturation were studied at various time points up to 24 h within each straining protocol. The results indicate that a period of static strain following cyclic strain favors collagen synthesis and remodeling, whereas ongoing cyclic strain shifts this balance toward collagen remodeling and maturation. The data suggest that, with prolonged culture, the conditioning protocol should be changed from intermittent straining to continuous cyclic straining to improve collagen maturation after its synthesis and, hence, the tissue (mechanical) properties. 相似文献
20.
The mechanisms governing the efficient tumor spheroid penetration and transport by poly(amidoamine) (PAMAM) dendrimers displaying varying numbers of cyclic RGD targeting peptides (2, 3, 7, or 10) were evaluated in this work. The cell-free binding affinities and cellular internalization kinetics of PAMAM-RGD conjugates to malignant glioma cells were determined experimentally, and the results were incorporated into a mathematical model to predict the transport of these materials through a multicellular tumor spheroid. The theoretical analysis demonstrated that greater RGD crosslinking may improve transport through tumor spheroids due to their decreased integrin-binding affinity. This study provides evidence that altering the density of tumor-targeting ligands from a drug delivery platform is a feasible way to optimize the tumor-penetration efficiency of an anticancer agent, and provides insight into the physicochemical mechanisms governing the relative effectiveness of these conjugates. 相似文献