Figure 1 - uploaded by Cornelia Kasper
Content may be subject to copyright.
Typical stress-strain curve obtained for sample 3 of S30-90HA. Young's modulus was measured as the slope in the linear elastic range (2), while the ultimate compressive stress is given at point (3).
Source publication
The experimental evidence of the dependence of cell proliferation and differentiation in vitro on the mechanical environment aims to the need of characterization of porous scaffolds in terms of mechanical and flow properties. In this sense, the Young's modulus and intrinsic permeability for three types of Sponceram(R) cell carriers developed for in...
Contexts in source publication
Context 1
... compression tests were carried out over five samples of each Sponceram 1 group. Sponceram 1 discs were cut using a scalpel to obtain the samples, each with a different size to account for size effects. Because of the brittle behavior of the Sponceram 1 discs, it was difficult to get uniform samples, although they were free of local dam- age. The exposed sample areas to the compression plates were processed using imaging software (Adobe Photo- shop 1 ). Compression tests were carried out using a micro tester Instron 1 machine in displacement-control rate of 0.1 mm/min, equivalent to a strain rate of 0.03 min 21 . The Young's modulus of each sample belonging to each group was estimated from the slope of the stress-strain curve in the linear elastic region. The ultimate compressive stress was determined at the point where the slope of stress-strain curve turns into negative. A typical stress-strain curve of a sample is plotted in Figure 1. Statistical analysis of the obtained values was performed with MATLAB 1 (Math- ...
Context 2
... mechanical behavior of these Sponceram 1 scaffolds was observed to be very brittle, due to the composition of the pore-free base material. A typical ceramic-like mechan- ical behavior was found, see Figure 1, where several well- distinguished zones may be observed. First, a nonlinear zone (1) due to sample-plate contact, followed by a linear elastic zone (2) where the Young's modulus may be esti- mated. At point (3) we found the maximum (ultimate) compressive stress before failure. After this, the curve decays (4) due to damage accumulation associated to for- mation and progression of cracks. In a ceramic-like mate- rial, the nonlinear plateau due to wall buckling, typical of porous materials, 37 is not usually presented. Final, when the specimen was completely collapsed, densification of the cracked material occurs at zone (5). According to the standard deviation of the experimental results, no size effect was observed for S30-90 and S30- 90HA and therefore we consider the samples representa- tives of the scaffold microstructure. S20-90 presented a higher dispersion which is assumed to be due to the walls of the scaffold are more slender and more receptive to de- velop cracks, being difficult to fit since these nonlinear phenomena were predominant in these samples. Because of the standard deviation found in the porosity for the RVEs taken from tomographies and comparing with data provided by Zellwerk, 32 we consider these RVEs representative of the scaffold microstructure. In terms of the computational analysis, no size effect was expected from the choice of the RVE due to the linearity of the problem solved. [38][39][40] Samples of S30-90HA were coated with Hydroxyapatite (HA). Besides, these samples presented lower porosity than S30-90, and as consequence, a higher Young's modulus as observed in Table II. It should be remarked that the HA effect seems to be not much relevant in the overall effec- tive mechanical behavior of S30-90HA, since the experi- mental values match very well with those obtained numerically where the HA layer was not ...
Similar publications
Background
Biodegradable stents display insufficient scaffold performance due to their poor Young’s Modulus. In addition, the corresponding biodegradable materials harbor weakened structures during degradation processes. Consequently, such stents have not been extensively applied in clinical therapy. In this study, the scaffold performance of a pat...
Iron oxide γ-Fe2O3 magnetic nanoparticles (MNPs) were fabricated by laser target evaporation technique (LTE) and their structure and magnetic properties were studied. Polyacrylamide (PAAm) gels with different cross-linking density of the polymer network and polyacrylamide-based ferrogel with embedded LTE MNPs (0.34 wt.%) were synthesized. Their adh...
Previously, single phase scaffold for bone tissue engineering were widely used for clinical applications. However, single phase scaffold is not sufficiently bioactive and lack of mechanical integrity, thus it was not suitable for such purpose. Hence, a new approach had been taken to produce composite scaffold by combining two or more biomaterials....
The structure and properties of scaffold are important in cell-based tissue engineering, especially the mechanical property. Here, we quantify the dynamic oscillatory mechanical behavior of two kinds of porous collagen/chitosan scaffolds. The Young's Modulus were measured in PBS using Atomic Force Microscopy (AFM)-based nano-indentation in response...
Citations
... Several methods have been proposed to characterize the scaffold permeability 9,11,19,24,25,[28][29][30][31][32][33] , however, a standardized protocol is missing also because the different proposed measurement techniques limit their applicability to specific scaffold structures, resulting in not comparable results 23 . Regarding the testing conditions, it is important to consider that TE scaffolds, whether designed for laboratory (in vitro) use or clinical applications, are typically used under physiologically relevant hydrated conditions, which can influence their structure and consequently their permeability. ...
Intrinsic permeability describes the ability of a porous medium to be penetrated by a fluid. Considering porous scaffolds for tissue engineering (TE) applications, this macroscopic variable can strongly influence the transport of oxygen and nutrients, the cell seeding process, and the transmission of fluid forces to the cells, playing a crucial role in determining scaffold efficacy. Thus, accurately measuring the permeability of porous scaffolds could represent an essential step in their optimization process. In literature, several methods have been proposed to characterize scaffold permeability. Most of the currently adopted approaches to assess permeability limit their applicability to specific scaffold structures, hampering protocols standardization, and ultimately leading to incomparable results among different laboratories. The content of novelty of this study is in the proposal of an adaptable test bench and in defining a specific testing protocol, compliant with the ASTM International F2952-22 guidelines, for reliable and repeatable measurements of the intrinsic permeability of TE porous scaffolds. The developed permeability test bench (PTB) exploits the pump-based method, and it is composed of a modular permeability chamber integrated within a closed-loop hydraulic circuit, which includes a peristaltic pump and pressure sensors, recirculating demineralized water. A specific testing protocol was defined for characterizing the pressure drop associated with the scaffold under test, while minimizing the effects of uncertainty sources. To assess the operational capabilities and performance of the proposed test bench, permeability measurements were conducted on PLA scaffolds with regular (PS) and random (RS) micro-architecture and on commercial bovine bone matrix-derived scaffolds (CS) for bone TE. To validate the proposed approach, the scaffolds were as well characterized using an alternative test bench (ATB) based on acoustic measurements, implementing a blind randomized testing procedure. The consistency of the permeability values measured using both the test benches demonstrated the reliability of the proposed approach. A further validation of the PTB’s measurement reliability was provided by the agreement between the measured permeability values of the PS scaffolds and the theory-based predicted permeability value. Once validated the proposed PTB, the performed measurements allowed the investigation of the scaffolds’ transport properties. Samples with the same structure (guaranteed by the fused-deposition modeling technique) were characterized by similar permeability values, and CS and RS scaffolds showed permeability values in agreement with the values reported in the literature for bovine trabecular bone. In conclusion, the developed PTB and the proposed testing protocol allow the characterization of the intrinsic permeability of porous scaffolds of different types and dimensions under controlled flow regimes, representing a powerful tool in view of providing a reliable and repeatable framework for characterizing and optimizing scaffolds for TE applications.
... It is also worth mentioning that with increasing porosity, the apparent scaffold stiffness decreases according to the square of porosity [106]. Thus, a scaffold should have a suitable porosity allowing sufficiently high permeability for waste removal and nutrient supply and appropriate stiffness to bear the loads conveyed to the scaffold from the surrounding healthy bone [105]. ...
Since 2006, the foam replica method has been commonly recognized as a valuable technology for the production of highly porous bioactive glass scaffolds showing three-dimensional, open-cell structures closely mimicking that of natural trabecular bone. Despite this, there are important drawbacks making the usage of foam-replicated glass scaffolds a difficult achievement in clinical practice; among these, certainly the high operator-dependency of the overall manufacturing process is one of the most crucial, limiting the scalability to industrial production and, thus, the spread of foam-replicated synthetic bone substitutes for effective use in routine management of bone defect. The present review opens a window on the versatile world of the foam replica technique, focusing the dissertation on scaffold properties analyzed in relation to various processing parameters, in order to better understand which are the real issues behind the bottleneck that still puts this technology on the Olympus of the most used techniques in laboratory practice, without moving, unfortunately, to a more concrete application. Specifically, scaffold morphology, mechanical and mass transport properties will be reviewed in detail, considering the various templates proposed till now by several research groups all over the world. In the end, a comprehensive overview of in vivo studies on bioactive glass foams will be provided, in order to put an emphasis on scaffold performances in a complex three-dimensional environment.
... So far, just a few works have dealt with the experimental validation of asymptotic homogenization of different transport mechanisms in porous media. These works have either dealt with strictly convective flow ( [20][21][22] ), exemplary investigated diffusion of liquid NaCl solution in water in a model periodic porous medium [23] or coupled convective fluid flow and heat transfer [24] . To the best of our knowledge, no research has dealt with the experimental validation of asymptotic homogenization of Knudsen diffusion in porous engineering materials. ...
Transport in porous media is central in chemical engineering. Effective transport properties are required for evaluating and improving many processes and applications. A widely used model to describe transport in porous media is the Dusty-gas model. This model accounts for permeation, Knudsen-diffusion and binary diffusion. The model parameters are commonly determined from experiments, for instance, performed in a Wicke-Kallenbach cell. The parameters derived in this way are spatially averaged effective parameters.
In this contribution, we present an approach to calculate transport parameters of the Dusty-Gas model from a cross-sectional image of the porous material, which often reduces experimental effort. The approach is also applicable to virtually designed materials for which structural information is available from simulations, but no physical sample has yet been synthesized.
The method applied here is asymptotic homogenization, which allows lumping structural information on the micro-scale into effective transport properties. In a previous contribution, we successfully demonstrated the calculation of effective permeability for a porous hollow fiber from image data. Here we extend the work to Knudsen diffusion and binary diffusion.
To validate our results, we compare model predictions for Knudsen-diffusion with experimental data from measurements in a Wicke-Kallenbach cell and predictions of the effective binary diffusion coefficient by comparison to literature data for a sphere packing.
... For this purpose, the homogenization theory was extensively applied during design [24][25][26]. In the same context, the asymptotic homogenization theory was applied to validate the experimental Darcian permeability and mechanical properties of a specific scaffold, Sponceram ® , available for BTE applications [27]. On the one hand, the homogenization theory computes the overall macroscopic stiffness tensor C 0 as follows, ...
... Scaffold permeability has been measured experimentally in several papers using pumped water [76,77], with a gravity-induced pressure using water [78][79][80] or using compressed air [81], to cite a few. Indeed, permeability was numerically validated using the homogenization theory versus an experimental gravity-induced pressure setup, for a specific commercial scaffold for BTE applications [27]. In the same context, Truscello et al. [82] validated the permeability values of Ti6Al4V scaffolds using CFD simulations. ...
Bone tissue engineering is currently a mature methodology from a research perspective. Moreover, modeling and simulation of involved processes and phenomena in BTE have been proved in a number of papers to be an excellent assessment tool in the stages of design and proof of concept through in-vivo or in-vitro experimentation. In this paper, a review of the most relevant contributions in modeling and simulation, in silico, in BTE applications is conducted. The most popular in silico simulations in BTE are classified into: (i) Mechanics modeling and scaffold design, (ii) transport and flow modeling, and (iii) modeling of physical phenomena. The paper is restricted to the review of the numerical implementation and simulation of continuum theories applied to different processes in BTE, such that molecular dynamics or discrete approaches are out of the scope of the paper. Two main conclusions are drawn at the end of the paper: First, the great potential and advantages that in silico simulation offers in BTE, and second, the need for interdisciplinary collaboration to further validate numerical models developed in BTE.
... Numerical results are always comparable showing a better fitting with the solution provided by [82] for the transverse permeability and [83] for the longitudinal one. This technique has been successfully applied for the determination of the permeability tensor, and hence the macroscopic Darcy's law, in woven structures [84,85], tissue engineering scaffolds [86][87][88] and porous materials [70,89]. This technique has been successfully applied for the determination of the permeability tensor, and hence the macroscopic Darcy's law, in woven structures [84,85], tissue engineering scaffolds [86][87][88] and porous materials [70,89]. ...
... This technique has been successfully applied for the determination of the permeability tensor, and hence the macroscopic Darcy's law, in woven structures [84,85], tissue engineering scaffolds [86][87][88] and porous materials [70,89]. This technique has been successfully applied for the determination of the permeability tensor, and hence the macroscopic Darcy's law, in woven structures [84,85], tissue engineering scaffolds [86][87][88] and porous materials [70,89]. This technique has been successfully applied for the determination of the permeability tensor, and hence the macroscopic Darcy's law, in woven structures [84,85], tissue engineering scaffolds [86][87][88] and porous materials [70,89]. ...
... This technique has been successfully applied for the determination of the permeability tensor, and hence the macroscopic Darcy's law, in woven structures [84,85], tissue engineering scaffolds [86][87][88] and porous materials [70,89]. This technique has been successfully applied for the determination of the permeability tensor, and hence the macroscopic Darcy's law, in woven structures [84,85], tissue engineering scaffolds [86][87][88] and porous materials [70,89]. ...
Computational multiscale analyses are currently ubiquitous in science and technology. Different problems of interest—e.g., mechanical, fluid, thermal, or electromagnetic—involving a domain with two or more clearly distinguished spatial or temporal scales, are candidates to be solved by using this technique. Moreover, the predictable capability and potential of multiscale analysis may result in an interesting tool for the development of new concept materials, with desired macroscopic or apparent properties through the design of their microstructure, which is now even more possible with the combination of nanotechnology and additive manufacturing. Indeed, the information in terms of field variables at a finer scale is available by solving its associated localization problem. In this work, a review on the algorithmic treatment of multiscale analyses of several problems with a technological interest is presented. The paper collects both classical and modern techniques of multiscale simulation such as those based on the proper generalized decomposition (PGD) approach. Moreover, an overview of available software for the implementation of such numerical schemes is also carried out. The availability and usefulness of this technique in the design of complex microstructural systems are highlighted along the text. In this review, the fine, and hence the coarse scale, are associated with continuum variables so atomistic approaches and coarse-graining transfer techniques are out of the scope of this paper.
... The Darcian permeability (K) was estimated with K = 10 -9 m 2 . [38][39][40] Since the flow through the microbioreactor was found to be highly laminar in the considered range of FRs (Re <1), the quadratic loss coefficient was not taken into account for the simulations. ...
Bioreactor-systems facilitate 3D-cell culture by coping with limitations of static cultivation techniques. To allow for the investigation of proper cultivation conditions and the reproducible generation of tissue-engineered grafts, a bioreactor-system, which comprises the control of crucial cultivation parameters in independent-operating parallel bioreactors, is beneficial. Furthermore, the use of a bioreactor as an automated cell seeding tool enables even cell distributions on stable scaffolds. In this study, we developed a perfusion microbioreactor-system, which enables the cultivation of 3D-cell cultures in an oxygen-controlled environment in up to four independent-operating bioreactors. Therefore, perfusion microbioreactors were designed with the help of computer-aided design (CAD) and manufactured using the 3D-printing technologies stereolithography (SLA) and fused deposition modeling (FDM). A uniform flow distribution in the microbioreactor, was shown with the help of a computational fluid dynamics (CFD) model. For oxygen measurements, microsensors were integrated in the bioreactors, to measure the oxygen concentration in the geometric center of the 3D-cell cultures. To control the oxygen concentration in each bioreactor independently, an automated feed-back loop was developed which adjusts the perfusion velocity according to the oxygen sensor signal. Furthermore, an automated cell seeding protocol was implemented, to facilitate the even distribution of cells within a stable scaffold in a reproducible way. As proof of concept, the human mesenchymal stem cell line SCP-1 was seeded on bovine cancellous bone matrix of 1 cm³ and cultivated in the developed microbioreactor-system at different oxygen levels. The oxygen control was capable to maintain preset oxygen levels +/- 0.5 % over a cultivation period of several days. Using the automated cell seeding procedure resulted in evenly distributed cells within a stable scaffold. In summary, the developed microbioreactor-system enables the cultivation of 3D-cell cultures in an automated and thus reproducible way by providing up to four independently operating, oxygen-controlled bioreactors. In combination with the automated cell seeding procedure, the bioreactor-system opens up new possibilities to conduct more reproducible experiments to investigate optimal cultivation parameters and to generate tissue-engineering grafts in an oxygen-controlled environment.
... Therefore, researchers have gone toward preparation of suitable structural frameworks named bone scaffold to provide a support for cells (Jariwala et al., 2015;Poh, 2014). Such structures should have appropriate geometrical and mechanical properties in order to provide suitable bone treatment (Giannitelli et al., 2014;Sanz-Herrera et al., 2008;Yang et al., 2001). In this regard, Dias et al. (2014) proposed a topology optimization algorithm for designing scaffolds that satisfy both mass transport and mechanical load bearing capacity. ...
In recent years, thanks to additive manufacturing technology, researchers have gone towards the optimization of bone scaffolds for the bone reconstruction. Bone scaffolds should have appropriate biological as well as mechanical properties in order to play a decisive role in bone healing. Since the fabrication of scaffolds is time consuming and expensive, numerical methods are often utilized to simulate their mechanical properties in order to find a nearly optimum one. Finite element analysis is one of the most common numerical methods that is used in this regard. In this paper, a parametric finite element model is developed to assess the effects of layers penetration׳s effect on inter-layer adhesion, which is reflected on the mechanical properties of bone scaffolds. To be able to validate this model, some compression test specimens as well as bone scaffolds are fabricated with biocompatible and biodegradable poly lactic acid using fused deposition modeling. All these specimens are tested in compression and their elastic modulus is obtained. Using the material parameters of the compression test specimens, the finite element analysis of the bone scaffold is performed. The obtained elastic modulus is compared with experiment indicating a good agreement. Accordingly, the proposed finite element model is able to predict the mechanical behavior of fabricated bone scaffolds accurately. In addition, the effect of post-heating of bone scaffolds on their elastic modulus is investigated. The results demonstrate that the numerically predicted elastic modulus of scaffold is closer to experimental outcomes in comparison with as-built samples.
... Indeed, theses results match up with a previous study by Sanz-Herrera et al. where the permeability of more porous (ε = 80 %) Sponceram was found to be k = 1.88·10 -8 m 2 [273]. Furthermore, permeability of cancellous bone was found to be approximately k = 2.1·10 -9 m 2 in the same study. ...
... where Q refers to the volumetric ow rate, µ is the dynamic viscosity of water at 37 • C, h is the height and A the area of the biomaterial. Permeability was determined for the ceramic zirconium dioxide matrix Sponceram which has been characterized extensively before and was shown to have bone-like properties [273]. It has a porosity of 66.7 %, an average pore size of 510 µm, a diameter of 10 mm and a thickness of 3 mm. ...
Mesenchymal stem cells (MSCs) are still considered as the primary candidate for cell-based therapies and tissue engineering products in Regenerative Medicine. They are easily accessible and ethically unobjectionable multipotent stem cells with remarkable properties such as high proliferation and differentiation capacity or the secretion of trophic factors involved in wound healing. For cell-based therapies MSCs are isolated from various tissues and expanded in vitro before they are applied to a patient. For tissue engineered products cells are seeded on three-dimensional (3D) matrices after expansion and then differentiated into a specific lineage. Those cell-seeded constructs are then used for transplantation or as in vitro models. In general, all steps of in vitro celll culture are traditionally carried out on two-dimensional (2D) plastic surfaces in a static conditions which does not represent the physiologic environment that cells are exposed to in vivo. In fact, the implementation of physiologic conditions, such as 3D scaffolds, mechanical forces or suitable oxygen concentrations were shown to influence cellular behavior significantly. Thus, in order to improve the predictability of basic research for clinical trials, the implementation of physiologic conditions seems desirable. Therefore, this work presents approaches and considerations for the implementation of physiologic conditions in the isolation, expansion and differentiation of MSCs. The isolation of adipose derived MSC by explant culture is compared to the traditional isolation by enzymatic digestion and the resulting cells were characterized towards their stem cell properties. Also, a novel approach for the expansion of MSCs was developed. For this, cells were cultivated as scaffold-free 3D aggregates in a continuously stirred tank reactor. Finally, a concept for the characterization and control of the mechanical environment in a perfused bioreactor for osteogenic differentiation of MSCs is presented. For this, the 3D matrices and the behavior of fluid elements in the bioreactor were characterized. Subsequently, a novel incubator system with integrated non-invasive pressure sensors was harnessed to screen and optimize mechanical conditions. Additionally, reduced oxygen concentrations were implemented in all phases of cultivation. On the one side, the presented results point out beneficial effects of physiologic conditions, on the other side it underlines the importance of diligent and comprehensive characterization of relevant cultivation parameters in order to define, generate and control physiologic conditions. These concepts for the implementation of physiologic conditions throughout the entire in vitro cultivation of MSCs are highly fundamental to improve translational research
... Porosity (66.7%) and average pore size (510 µm) were derived from µCT scans (data not shown). It was shown to have bone-like properties [25] and thus was suggested to be a suitable matrix for bone tissue engineering processes. The scaffold discs used in this study were 10 mm in diameter and 3 mm in thickness. ...
... Therefore, the average of the calculated k-values from 9 to 15 mL/min (k = 1.7 ± 0.9 × 10 −10 m 2 ) was inserted in the shear stress equations and the computational model. Similarly, the permeability of Sponceram with a higher porosity (80%) than the Sponceram discs used in this study was found to be k = 1.88 × 10 −8 m 2 and the permeability of cancellous bone was approximately 2.1 × 10 −9 m 2 as reported before [25]. The lower permeability measured in the present study can be attributed to the lower porosity (67%) of Sponceram used in this study. ...
The three dimensional (3D) cultivation of stem cells in dynamic bioreactor systems is essential in the context of regenerative medicine. Still, there is a lack of bioreactor systems that allow the cultivation of multiple independent samples under different conditions while ensuring comprehensive control over the mechanical environment. Therefore, we developed a miniaturized, parallelizable perfusion bioreactor system with two different bioreactor chambers. Pressure sensors were also implemented to determine the permeability of biomaterials which allows us to approximate the shear stress conditions. To characterize the flow velocity and shear stress profile of a porous scaffold in both bioreactor chambers, a computational fluid dynamics analysis was performed. Furthermore, the mixing behavior was characterized by acquisition of the residence time distributions. Finally, the effects of the different flow and shear stress profiles of the bioreactor chambers on osteogenic differentiation of human mesenchymal stem cells were evaluated in a proof of concept study. In conclusion, the data from computational fluid dynamics and shear stress calculations were found to be predictable for relative comparison of the bioreactor geometries, but not for final determination of the optimal flow rate. However, we suggest that the system is beneficial for parallel dynamic cultivation of multiple samples for 3D cell culture processes.
... Porosity (66.7%) and average pore size (510 µm) were derived from µCT scans (data not shown). It was shown to have bone-like properties [25] and thus was suggested to be a suitable matrix for bone tissue engineering processes. The scaffold discs used in this study were 10 mm in diameter and 3 mm in thickness. ...
... Therefore, the average of the calculated k-values from 9 to 15 mL/min (k = 1.7 ± 0.9 × 10 −10 m 2 ) was inserted in the shear stress equations and the computational model. Similarly, the permeability of Sponceram with a higher porosity (80%) than the Sponceram discs used in this study was found to be k = 1.88 × 10 −8 m 2 and the permeability of cancellous bone was approximately 2.1 × 10 −9 m 2 as reported before [25]. The lower permeability measured in the present study can be attributed to the lower porosity (67%) of Sponceram used in this study. ...
It is crucial but challenging to keep physiologic conditions during the cultivation of 3D cell scaffold constructs for the optimization of 3D cell culture processes. Therefore, we demonstrate the benefits of a recently developed miniaturized perfusion bioreactor together with a specialized incubator system that allows for the cultivation of multiple samples while screening different conditions. Hence, a decellularized bone matrix was tested towards its suitability for 3D osteogenic differentiation under flow perfusion conditions. Subsequently, physiologic shear stress and hydrostatic pressure (HP) conditions were optimized for osteogenic differentiation of human mesenchymal stem cells (MSCs). X-ray computed microtomography and scanning electron microscopy (SEM) revealed a closed cell layer covering the entire matrix. Osteogenic differentiation assessed by alkaline phosphatase activity and SEM was found to be increased in all dynamic conditions. Furthermore, screening of different fluid shear stress (FSS) conditions revealed 1.5 mL/min (equivalent to ∼10 mPa shear stress) to be optimal. However, no distinct effect of HP compared to flow perfusion without HP on osteogenic differentiation was observed. Notably, throughout all experiments, cells cultivated under FSS or HP conditions displayed increased osteogenic differentiation, which underlines the importance of physiologic conditions. In conclusion, the bioreactor system was used for biomaterial testing and to develop and optimize a 3D cell culture process for the osteogenic differentiation of MSCs. Due to its versatility and higher throughput efficiency, we hypothesize that this bioreactor/incubator system will advance the development and optimization of a variety of 3D cell culture processes.
