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International Journal of Bioprinting                              Design and optimization of 3DP bioscaffolds





























                           Figure 13. Cell counts for the multi-channel scaffolds with different volume fraction of channel on day 7.

            fraction equaled to 7.5% (Figure 12e). This is attributed to   exhibited the highest cell numbers on day 7 compared to
            the interplay between the increase in cell density and the   others,  confirming  the  effectiveness of  this  optimization
            reduction of scaffold materials for carrying cells. Note that   method.
            this value may vary when other parameters differ, such as   Channels or  voids  are  key architectural features  in
            the height and diameter of the scaffold, cell type, scaffold   scaffolds,  providing  a  passageway  to  guide  cell  growth
            material, and nutrient flow conditions. The second step is   and facilitating  nutrient and waste  exchange. 11,14,15  The
            to spread the single-channel volume fraction (7.5% for this   degree of cellularity  in scaffolds is critical to ensure the
            case) to the scaffold to form a multi-channeled scaffold   biological functionalities of the engineering tissue, and
            with optimal geometric parameters, including channel   highly cellularized scaffolds can enhance intercellular and
            diameter and number (see Figure 12f). When the number   cell–material interactions, therefore improving cellular
            of channels increased from 1 to 21, the normalized average   behaviors.  During the design of porous scaffolds, adding
                                                                       45
            oxygen concentration rose from 23.2% to 40.95% (Figure   more empty phases can improve the permeability and thus
            12g). The volume fraction of the hypoxic region, where the   cell proliferation; however, it reduces the solid volume for
            oxygen concentration was lower than the threshold C <14   carrying cells. The correct geometric parameters of scaffolds
            μM,  decreased from 46.02% to only 8.18% (Figure 12h).   yielding maximum cell number should be determined, in
               20
            As a result, the number of cells elevated from 1,082,166 to   order to maximize the cellularity degree of the scaffolds.
            1,492,918, showing an increment  of  37.96% (Figure 12i   However, the selection of channel parameters is somewhat
            and j). The specific surface area is a critical indicator to   arbitrary in current practice or based on experiments, and
            characterize the performance of scaffold as it influences   the current design rules are insufficient to obtain the most
            the  rate  of  oxygen  and  nutrients  exchange  significantly.   optimal parameters. The results showed that the channel
            The specific surface area increases when increasing the   number and size significantly impact cell proliferation.
            void volume fraction (Figure 12a) or splitting the empty   Simply adding channels improves oxygen transportation
            phase into more tiny channels (Figure 12f). The specific   and cell density. However, excessive channels will reduce
            surface area is enlarged from 1.5 to 2.35 when the number   the scaffold materials and thus the final cell number. The
            of channels increases from 1 to 21 (Figure 12f), indicating   modeling-based optimization strategy proposed in this
            that scaffolds featuring more tiny channels possess better   study can determine the optimal channel parameters that
            permeability and therefore higher cell growth rates. This   ensure maximum cell number after culturing. For this
            is consistent with the modeled cell density (Figure 12i),   case, the optimal scaffold features 21 uniformly distributed
            further verifying the correctness of the model. To validate   channels with a diameter of 0.3 mm. Theoretically, the
            that the structure with multiple channels was optimal, a   cell  count  can  be  further  improved by  increasing the
            similar procedure was applied for scaffolds with channel   channel number to more than 21. Scaffolds with desired
            volume fractions of 5% and 10% for comparison. As shown   permeability and cell proliferation are usually geometrically
            in Figure 13, the scaffolds with a volume fraction of 7.5%   complex and feature microsized channels and thin walls,


            Volume 10 Issue 3 (2024)                       296                                doi: 10.36922/ijb.1838
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