In this article, we identify and discuss a timeline of historical events and scientific breakthro... more In this article, we identify and discuss a timeline of historical events and scientific breakthroughs that shaped the principles of tissue engineering and regenerative medicine (TERM). We explore the origins of TERM concepts in myths, their application in the ancient era, their resurgence during Enlightenment, and, finally, their systematic codification into an emerging scientific and technological framework in recent past. The development of computational/mathematical approaches in TERM is also briefly discussed.
Capturing the dynamism that pervades biological systems requires a computational approach that ca... more Capturing the dynamism that pervades biological systems requires a computational approach that can accommodate both the continuous features of the system environment as well as the flexible and heterogeneous nature of component interactions. This presents a serious challenge for the more traditional mathematical approaches that assume component homogeneity to relate system observables using mathematical equations. While the homogeneity condition does not lead to loss of accuracy while simulating various continua, it fails to offer detailed solutions when applied to systems with dynamically interacting heterogeneous components. As the functionality and architecture of most biological systems is a product of multi-faceted individual interactions at the sub-system level, continuum models rarely offer much beyond qualitative similarity. Agent-based modelling is a class of algorithmic computational approaches that rely on interactions between Turing-complete finite-state machinesçor agentsçto simulate, from the bottom-up, macroscopic properties of a system. In recognizing the heterogeneity condition, they offer suitable ontologies to the system components being modelled, thereby succeeding where their continuum counterparts tend to struggle. Furthermore, being inherently hierarchical, they are quite amenable to coupling with other computational paradigms. The integration of any agent-based framework with continuum models is arguably the most elegant and precise way of representing biological systems. Although in its nascence, agent-based modelling has been utilized to model biological complexity across a broad range of biological scales (from cells to societies). In this article, we explore the reasons that make agent-based modelling the most precise approach to model biological systems that tend to be non-linear and complex.
Despite numerous technology advances, bioreactors are still mostly utilized as functional black-b... more Despite numerous technology advances, bioreactors are still mostly utilized as functional black-boxes where trial and error eventually leads to the desirable cellular outcome. Investigators have applied various computational approaches to understand the impact the internal dynamics of such devices has on overall cell growth, but such models cannot provide a comprehensive perspective regarding the system dynamics, due to limitations inherent to the underlying approaches. In this study, a novel multi-paradigm modeling platform capable of simulating the dynamic bidirectional relationship between cells and their microenvironment is presented. Designing the modeling platform entailed combining and coupling fully an agent-based modeling platform with a transport phenomena computational modeling framework. To demonstrate capability, the platform was used to study the impact of bioreactor parameters on the overall cell population behavior and vice versa. In order to achieve this, virtual bioreactors were constructed and seeded. The virtual cells, guided by a set of rules involving the simulated mass transport inside the bioreactor, as well as cell-related probabilistic parameters, were capable of displaying an array of behaviors such as proliferation, migration, chemotaxis and apoptosis. In this way the platform was shown to capture not only the impact of bioreactor transport processes on cellular behavior but also the influence that cellular activity wields on that very same local mass transport, thereby influencing overall cell growth. The platform was validated by simulating cellular chemotaxis in a virtual direct visualization chamber and comparing the simulation with its experimental analogue. The results presented in this paper are in agreement with published models of similar flavor. The modeling platform can be used as a concept selection tool to optimize bioreactor design specifications. Citation: Kaul H, Cui Z, Ventikos Y (2013) A Multi-Paradigm Modeling Framework to Simulate Dynamic Reciprocity in a Bioreactor. PLoS ONE 8(3): e59671.
This Journal publishes works in all fields of microscopical morphology; high quality is the overa... more This Journal publishes works in all fields of microscopical morphology; high quality is the overall consideration. HISTOLOGY AND HISTOPATHOLOGY is an international journal, the purpose of which is to publish original works in English in histology, histopathology and cell biology. Its format is the standard international size of 21 x 27.7 cm. One volume is published every year. Each volume consists of 12 numbers published monthly online. The printed version of the journal includes 4 books every year; each of them compiles 3 numbers previously published online. The price per volume, including postage by surface mail and free online access, is 550 euros (or US $700) for 2011. Impact factor: 2.404. Journal Citation Report ® 2009, published by Thomson Scientific.
Clinical Orthopaedics and Related Research®, Jul 2009
Since low-dose antibiotic-loaded bone cement (ALBC) was approved by the FDA for second-stage reim... more Since low-dose antibiotic-loaded bone cement (ALBC) was approved by the FDA for second-stage reimplantation after infected arthroplasties in 2003, commercially premixed low-dose ALBC has become available in the United States. However, surgeons continue to mix ALBC by hand. We presumed hand-mixed ALBC was not as homogeneous as commercially premixed ALBC. We assessed homogeneity by determining the variation in antibiotic elution by location in a batch, from premixed and hand-mixed formulations of low-dose ALBC. Four hand-mixed methodologies were used: (1) suspension—antibiotic powder in the liquid monomer; (2) no-mix—antibiotic powder added but not mixed with the polymer powder before adding monomer; (3) hand-stirred—antibiotic powder stirred into the polymer powder before the monomer was added; and (4) bowl-mix—antibiotic powder mixed into polymer powder using a commercial mixing bowl before the monomer was added. Antibiotic elution was measured using the Kirby-Bauer bioassay. None of the mixing methods had consistently dissimilar homogeneity of antibiotic distribution from the others. Based upon our data we conclude hand-mixed low-dose ALBC is not less homogeneous than commercially premixed formulations.
In this article, we identify and discuss a timeline of historical events and scientific breakthro... more In this article, we identify and discuss a timeline of historical events and scientific breakthroughs that shaped the principles of tissue engineering and regenerative medicine (TERM). We explore the origins of TERM concepts in myths, their application in the ancient era, their resurgence during Enlightenment, and, finally, their systematic codification into an emerging scientific and technological framework in recent past. The development of computational/mathematical approaches in TERM is also briefly discussed.
Capturing the dynamism that pervades biological systems requires a computational approach that ca... more Capturing the dynamism that pervades biological systems requires a computational approach that can accommodate both the continuous features of the system environment as well as the flexible and heterogeneous nature of component interactions. This presents a serious challenge for the more traditional mathematical approaches that assume component homogeneity to relate system observables using mathematical equations. While the homogeneity condition does not lead to loss of accuracy while simulating various continua, it fails to offer detailed solutions when applied to systems with dynamically interacting heterogeneous components. As the functionality and architecture of most biological systems is a product of multi-faceted individual interactions at the sub-system level, continuum models rarely offer much beyond qualitative similarity. Agent-based modelling is a class of algorithmic computational approaches that rely on interactions between Turing-complete finite-state machinesçor agentsçto simulate, from the bottom-up, macroscopic properties of a system. In recognizing the heterogeneity condition, they offer suitable ontologies to the system components being modelled, thereby succeeding where their continuum counterparts tend to struggle. Furthermore, being inherently hierarchical, they are quite amenable to coupling with other computational paradigms. The integration of any agent-based framework with continuum models is arguably the most elegant and precise way of representing biological systems. Although in its nascence, agent-based modelling has been utilized to model biological complexity across a broad range of biological scales (from cells to societies). In this article, we explore the reasons that make agent-based modelling the most precise approach to model biological systems that tend to be non-linear and complex.
Despite numerous technology advances, bioreactors are still mostly utilized as functional black-b... more Despite numerous technology advances, bioreactors are still mostly utilized as functional black-boxes where trial and error eventually leads to the desirable cellular outcome. Investigators have applied various computational approaches to understand the impact the internal dynamics of such devices has on overall cell growth, but such models cannot provide a comprehensive perspective regarding the system dynamics, due to limitations inherent to the underlying approaches. In this study, a novel multi-paradigm modeling platform capable of simulating the dynamic bidirectional relationship between cells and their microenvironment is presented. Designing the modeling platform entailed combining and coupling fully an agent-based modeling platform with a transport phenomena computational modeling framework. To demonstrate capability, the platform was used to study the impact of bioreactor parameters on the overall cell population behavior and vice versa. In order to achieve this, virtual bioreactors were constructed and seeded. The virtual cells, guided by a set of rules involving the simulated mass transport inside the bioreactor, as well as cell-related probabilistic parameters, were capable of displaying an array of behaviors such as proliferation, migration, chemotaxis and apoptosis. In this way the platform was shown to capture not only the impact of bioreactor transport processes on cellular behavior but also the influence that cellular activity wields on that very same local mass transport, thereby influencing overall cell growth. The platform was validated by simulating cellular chemotaxis in a virtual direct visualization chamber and comparing the simulation with its experimental analogue. The results presented in this paper are in agreement with published models of similar flavor. The modeling platform can be used as a concept selection tool to optimize bioreactor design specifications. Citation: Kaul H, Cui Z, Ventikos Y (2013) A Multi-Paradigm Modeling Framework to Simulate Dynamic Reciprocity in a Bioreactor. PLoS ONE 8(3): e59671.
This Journal publishes works in all fields of microscopical morphology; high quality is the overa... more This Journal publishes works in all fields of microscopical morphology; high quality is the overall consideration. HISTOLOGY AND HISTOPATHOLOGY is an international journal, the purpose of which is to publish original works in English in histology, histopathology and cell biology. Its format is the standard international size of 21 x 27.7 cm. One volume is published every year. Each volume consists of 12 numbers published monthly online. The printed version of the journal includes 4 books every year; each of them compiles 3 numbers previously published online. The price per volume, including postage by surface mail and free online access, is 550 euros (or US $700) for 2011. Impact factor: 2.404. Journal Citation Report ® 2009, published by Thomson Scientific.
Clinical Orthopaedics and Related Research®, Jul 2009
Since low-dose antibiotic-loaded bone cement (ALBC) was approved by the FDA for second-stage reim... more Since low-dose antibiotic-loaded bone cement (ALBC) was approved by the FDA for second-stage reimplantation after infected arthroplasties in 2003, commercially premixed low-dose ALBC has become available in the United States. However, surgeons continue to mix ALBC by hand. We presumed hand-mixed ALBC was not as homogeneous as commercially premixed ALBC. We assessed homogeneity by determining the variation in antibiotic elution by location in a batch, from premixed and hand-mixed formulations of low-dose ALBC. Four hand-mixed methodologies were used: (1) suspension—antibiotic powder in the liquid monomer; (2) no-mix—antibiotic powder added but not mixed with the polymer powder before adding monomer; (3) hand-stirred—antibiotic powder stirred into the polymer powder before the monomer was added; and (4) bowl-mix—antibiotic powder mixed into polymer powder using a commercial mixing bowl before the monomer was added. Antibiotic elution was measured using the Kirby-Bauer bioassay. None of the mixing methods had consistently dissimilar homogeneity of antibiotic distribution from the others. Based upon our data we conclude hand-mixed low-dose ALBC is not less homogeneous than commercially premixed formulations.
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