The tissue engineering scaffold acts as an extracellular matrix that interacts to the cells prior to forming new tissues. The chemical and structural characteristics of scaffolds are major concerns in fabricating of ideal three-dimensional structure for tissue engineering applications. The polymer scaffolds used for tissue engineering should possess proper architecture and mechanical properties in addition to supporting cell adhesion, proliferation, and differentiation. Much research has been done on the topic of polymeric scaffold properties such as surface topographic features (roughness and hydrophilicity) and scaffold microstructures (pore size, porosity, pore interconnectivity, and pore and fiber architectures) that influence the cell-scaffold interactions. In this review, efforts were given to evaluate the effect of both chemical and structural characteristics of scaffolds on cell behaviors such as adhesion, proliferation, migration, and differentiation. This review would provide the fundamental information which would be beneficial for scaffold design in future. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 431-459, 2017.

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Dynamic-based systems are bio-designed in order to mimic the micro-environments of the bone tissue. There is limited direct comparison between perfusion and perfusion-rotation forces in designing a bioreactor. Hence, in current study, we aimed to compare given bioreactors for bone regeneration. Two types of bioreactors including rotating & perfusion and perfusion bioreactors were designed. Mesenchymal stem cells derived from buccal fat pad were loaded on a gelatin/ β-Tricalcium phosphate scaffold. Cell-scaffold constructs were subjected to different treatment condition and place in either of the bioreactors. Effect of different dynamic conditions on cellular behavior including cell proliferation, cell adhesion and osteogenic differentiation were assessed.Osteogenic assessment of scaffolds after 24 days revealed that rotating & perfusion bioreactor led to significantly higher expression of OCN and RUNX2 genes and also greater amount of ALP and collagen I protein production compared to static groups and perfusion bioreactor. Observation of cellular sheets which filled the scaffold porosities in SEM images, approved the better cell responses to rotating & perfusion forces of the bioreactor. The outcomes demonstrated that rotating & perfusion bioreactor action on bone regeneration is much preferable than perfusion bioreactor. Therefore, it seems that exertion of multi-stimuli is more effective for bone engineering.

The use of cell‐free scaffolds containing bioactive molecules having a controlled released pattern has been proposed as a promising approach in field of tissue engineering. This system would eliminate the challenges associated with cell implantation. For bone tissue engineering, in particular, the environment in favor of both de novo bone formation and vascularization are considered critical approach. Erythropoietin (EPO) has been shown to have bone‐related pleiotropic effects. However, due to the adverse systemic side effect, its local administration with controlled release has been recommended. This study aimed to fabricate erythropoietin (EPO)‐releasing poly lactic acid (PLA)/nanoclay (NC)/nanohydroxyaptitite (nHA) as a new scaffold for bone tissue engineering application. PLA/NC/nHA‐EPO scaffolds were fabricated using thermally induced phase separation technique. The fabricated scaffolds were first characterized in terms of morphology and physical properties, as well as their EPO realizing pattern. Then, their biocompatibility was assessed in response to the MG‐63 human osteoblast‐like cell line. Finally, its bone regeneration capability was evaluated in a rat calvarial model. The result showed that the fabricated scaffolds presented acceptable physical properties with the sustained release of EPO. The in vitro biocompatibility was also approved. Their bone regeneration in rat calvaria showed that the PLA/NC/nHA‐EPO scaffolds were significantly able to generate bone formation (41% after 8 weeks). Also, the formation of new vessels and capillaries were evident. The presence of osteoblast in the defect also confirmed that the EPO was potent in inducing mesenchymal stem cells chemotaxis. The PLA/NC/nHA containing EPO could be a promising cell‐free bioscaffold for bone tissue regeneration.

Bioreactor system has been used in bone tissue engineering in order to simulate dynamic nature of bone tissue environments. Perfusion bioreactors have been reported as the most efficient types of shear-loading bioreactor. Also, combination of forces, such as rotation plus perfusion, has been reported to enhance cell growth and osteogenic differentiation. Mathematical modeling using sophisticated infrastructure processes could be helpful and streamline the development of functional grafts by estimating and defining an effective range of bioreactor settings for better augmentation of tissue engineering. This study is aimed to conduct computational modeling for newly designed bioreactors in order to alleviate the time and material consuming for evaluating bioreactor parameters and effect of fluid flow hydrodynamics (various amounts of shear stress) on osteogenesis. Also, biological assessments were performed in order to validate similar parameters under implementing the perfusion or rotating and perfusion fluid motions in bioreactors’ prototype. Finite element method was used to investigate the effect of hydrodynamic of fluid flow inside the bioreactors. The equations used in the simulation to calculate the velocity values and consequently the shear stress values include Navier–Stokes and Brinkman equations. It has been shown that rotational fluid motion in rotating and perfusion bioreactor produces more velocity and shear stress compared with perfusion bioreactor. Moreover, implementing the perfusion together with rotational force in rotating and perfusion bioreactors has been shown to have more cell proliferation and higher activity of alkaline phosphatase enzyme as well as formation of extra cellular matrix sheet, as an indicator of bone-like tissue formation.