• Biotechnology and Bioprocess Engineering:BBE
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• v.6 no.5
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• pp.311-325
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• 2001

Tissue engineering scaffolds play a critical role in regulating the reconstructed human tissue development. Various types of scaffolds have been developed in recent years, including fibrous matrix and foam-like scaffolds. The design of scaffold materials has been investigated extensively. However, the design of physical structure of the scaffold, especially fibrous matrices, has not received much attention. This paper compares the different characteristics of fibrous and foam-like scaffolds, and reviews regulatory roles of important scaffold properties, including surface geometry, scaffold configuration, pore structure, mechanical property and bioactivity. Tissue regeneration, cell organization, proliferation and differentiation under different microstructures were evaluated. The importance of proper scaffold selection and design is further discussed with the examples of bone tissue engineering and stem cell tissue engineering. This review addresses the importance of scaffold microstructure and provides insights in designing appropriate scaffold structure for different applications of tissue engineering.

• Tissue Engineering and Regenerative Medicine
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• v.15 no.6
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• pp.673-697
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• 2018

BACKGROUND: Cartilage tissue engineering (CTE) aims to obtain a structure mimicking native cartilage tissue through the combination of relevant cells, three-dimensional scaffolds, and extraneous signals. Implantation of 'matured' constructs is thus expected to provide solution for treating large injury of articular cartilage. Type I collagen is widely used as scaffolds for CTE products undergoing clinical trial, owing to its ubiquitous biocompatibility and vast clinical approval. However, the long-term performance of pure type I collagen scaffolds would suffer from its limited chondrogenic capacity and inferior mechanical properties. This paper aims to provide insights necessary for advancing type I collagen scaffolds in the CTE applications. METHODS: Initially, the interactions of type I/II collagen with CTE-relevant cells [i.e., articular chondrocytes (ACs) and mesenchymal stem cells (MSCs)] are discussed. Next, the physical features and chemical composition of the scaffolds crucial to support chondrogenic activities of AC and MSC are highlighted. Attempts to optimize the collagen scaffolds by blending with natural/synthetic polymers are described. Hybrid strategy in which collagen and structural polymers are combined in non-blending manner is detailed. RESULTS: Type I collagen is sufficient to support cellular activities of ACs and MSCs; however it shows limited chondrogenic performance than type II collagen. Nonetheless, type I collagen is the clinically feasible option since type II collagen shows arthritogenic potency. Physical features of scaffolds such as internal structure, pore size, stiffness, etc. are shown to be crucial in influencing the differentiation fate and secreting extracellular matrixes from ACs and MSCs. Collagen can be blended with native or synthetic polymer to improve the mechanical and bioactivities of final composites. However, the versatility of blending strategy is limited due to denaturation of type I collagen at harsh processing condition. Hybrid strategy is successful in maximizing bioactivity of collagen scaffolds and mechanical robustness of structural polymer. CONCLUSION: Considering the previous improvements of physical and compositional properties of collagen scaffolds and recent manufacturing developments of structural polymer, it is concluded that hybrid strategy is a promising approach to advance further collagen-based scaffolds in CTE.

• Journal of Biomedical Engineering Research
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• v.29 no.4
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• pp.255-266
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• 2008

In tissue engineering, scaffolds play an important role in the growth of cells to 3-D organs or tissues. For the success of tissue engineering, they should be mimicked to meet the requirements of natural extracellular matrix (ECM) in the body, such as mechanical properties, adhesiveness, porosity, biodegradability, and growth factor release, etc. Contrary to other materials, polymeric materials are adequate to engineer scaffolds for tissue engineering because controlling the structure and the ratio of components and designing various shapes and size are possible. In this review, the importance, major characteristics, processes, and recent examples of polymeric scaffolds for tissue engineering applications are discussed.

• Proceedings of the Korean Institute of Surface Engineering Conference
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• 2017.05a
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• pp.3-23
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• 2017

The achievement of tissue engineering can be highly depending on the capability to generate complicated, cell seeded three dimensional (3D) micro/nano-structures. So, various fabrication techniques that can be used to precisely design the architecture and topography of scaffolding materials will signify a key aspect of multi-functional tissue engineering. Previous methods for obtaining scaffolds based on top-down are often not satisfactory to produce complex micro/nano-structures due to the lack of control on scaffold architecture, porosity, and cellular interactions. However, a bioprinting method can be used to design sophisticated 3D tissue scaffolds that can be engineered to mimic the tissue architecture using computer aided approach. Also, in recent, the method has been modified and optimized to fabricate scaffolds using various natural biopolymers (collagen, alginate, and chitosan etc.). Variation of the topological structure and polymer concentration allowed tailoring the physical and biological properties of the scaffolds. In this presentation, the 3D bioprinting supplemented with a newly designed plasma treatment for attaining highly bioactive and functional scaffolds for tissue engineering applications will be introduced. Moreover, various in vivo and in vitro results will show that the fabricated scaffolds can carry out their structural and biological functionality.

• Journal of Industrial and Engineering Chemistry
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• v.67
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• pp.388-395
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• 2018

Significant efforts have been applied toward fabricating three-dimensional (3D) scaffolds using 3D-bioprinting tissue engineering techniques. Gelatin has been used in 3D-bioprinting to produce designed 3D scaffolds; however, gelatin has a poor printability and is not useful for fabricating desired 3D scaffolds using 3D-bioprinting. In this study, we fabricated pore size controlled 3D gelatin scaffolds with two step 3D-bioprinting approach: a low-temperature ($-10^{\circ}C$) freezing step and a crosslinking process. The scaffold was crosslinked with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). The pore sizes of the produced 3D gelatin scaffolds were approximately 30% smaller than the sizes of the designed pore sizes. The surface morphologies and pore sizes of the 3D gelatin scaffolds were confirmed and measured using scanning electron microscopy (SEM). Human dermal fibroblasts (HDFs) were cultured on a 3D gelatin scaffold to evaluate the effect of the 3D gelatin scaffold pore size on the cell proliferation. After 14 days of culture, HDFs proliferation throughout the 3D gelatin scaffolds prepared with more than $580{\mu}m$ pore size was approximately 14% higher than proliferation throughout the 3D gelatin scaffold prepared with a $435{\mu}m$ pore size. These results suggested that control over the 3D gelatin scaffold pore size is important for tissue engineering scaffolds.

• Proceedings of the KSME Conference
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• 2008.11a
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• pp.1409-1410
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• 2008

Layer manufacturing technology has been recently spotlighted as a promising candidate to fabricate porous scaffolds for tissue engineering, because it can provide three dimensional interconnectivity and different pore structures and on-demand scaffold design. This study aims to fabricate HA/PCL composite scaffolds for bone tissue engineering by a layer manufacturing technology, paste extruding deposition, and to characterize in vitro and in vivo biocompatibilities of the scaffolds. This study discusses the mechnical properties, proliferation and differentiation of osteogenic cells, and tissue in-growth and bone regeneration behavior using animal models.

• Transactions of the Korean Society of Mechanical Engineers B
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• v.35 no.11
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• pp.1237-1242
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• 2011

Calcium phosphates are very interesting materials for use as scaffolds for bone tissue engineering. These materials include hydroxyapatite (HA) and tricalcium phosphate (TCP), which are inorganic components of human bone tissue and are both biocompatible and osteoconductive. Although these materials have excellent properties for use as bone scaffolds, many researchers have used these materials as additives to synthetic polymer scaffolds for bone tissue regeneration, because they are difficult to manufacture three-dimensional (3D) scaffolds. In this study, we fabricated 3D calcium phosphate scaffolds with the desired inner and outer architectures using solid freeform fabrication technology. To fabricate the scaffold, the sintering behavior was evaluated for various sintering temperatures and slurry concentrations. After the fabrication of the calcium phosphate scaffolds, in-vitro cell proliferation and osteogenic differentiation tests were carried out.

• Journal of Computational Design and Engineering
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• v.3 no.4
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• pp.385-397
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• 2016

Scaffolds are essential in bone tissue engineering, as they provide support to cells and growth factors necessary to regenerate tissue. In addition, they meet the mechanical function of the bone while it regenerates. Currently, the multiple methods for designing and manufacturing scaffolds are based on regular structures from a unit cell that repeats in a given domain. However, these methods do not resemble the actual structure of the trabecular bone which may work against osseous tissue regeneration. To explore the design of porous structures with similar mechanical properties to native bone, a geometric generation scheme from a reaction-diffusion model and its manufacturing via a material jetting system is proposed. This article presents the methodology used, the geometric characteristics and the modulus of elasticity of the scaffolds designed and manufactured. The method proposed shows its potential to generate structures that allow to control the basic scaffold properties for bone tissue engineering such as the width of the channels and porosity. The mechanical properties of our scaffolds are similar to trabecular tissue present in vertebrae and tibia bones. Tests on the manufactured scaffolds show that it is necessary to consider the orientation of the object relative to the printing system because the channel geometry, mechanical properties and roughness are heavily influenced by the position of the surface analyzed with respect to the printing axis. A possible line for future work may be the establishment of a set of guidelines to consider the effects of manufacturing processes in designing stages.

• Macromolecular Research
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• v.10 no.3
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• pp.158-167
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• 2002

In order to endow with new bioactive functionality from small intestine submucosa (SIS) powder as natural source to poly (L-lactide) (PLA) and poly (lactide-co-glycolide) (PLGA) synthetic biodegradable polymer, porous SIS/PLA and SIS/PLGA as natural/synthetic composite scaffolds were prepared by means of the solvent casting/salt leaching methods for the possibility of the application of tissue engineered bone and cartilage. A uniform distribution of good interconnected pores from the surface to core region was observed the pore size of 40~500 ${\mu}{\textrm}{m}$ independent with SIS amount using the solvent casting/salt leaching method. Porosities, specific pore areas as well as pore size distribution also were almost same. After the fabrication of SIS/PLA hybrid scaffolds, the wetting properties was greatly enhanced resulting in more uniform cell seeding and distribution. Five groups as PGA non-woven mesh without glutaraldehyde (GA) treatment, PLA scaffold without or with GA treatment, and SIS/PLA (Code No.3 ; 1 : 12 of salt content, (0.4 : 1 of SIS content, and 144 ${\mu}{\textrm}{m}$ of median pore size) without or with GA treatment were implanted into the back of nude mouse to observe the effect of SIS on the induction of cells proliferation by hematoxylin and eosin, and von Kossa staining for 8 weeks. It was observed that the effect of SIS/PLA scaffolds with GA treatment on bone induction are stronger than PLA scaffolds, that is to say, in the order of PLA/SIS scaffolds with GA treatment > PLA/SIS scaffolds without GA treatment > PGA nonwoven > PLA scaffolds only with GA treatment = PLA scaffolds only without GA treatment for the osteoinduction activity. The possible explanations are (1) many kinds of secreted, circulating, and extracellular matrix-bound growth factors from SIS to significantly affect critical processes of tissue development and differentiation, (2) the exposure of SIS to GA resulted in significantly calcification, and (3) peri-implant fibrosis due to covalent bonding between collagen molecule by crosslinking reaction. In conclusion, it seems that SIS plays an important role for bone induction in SIS/PLA scaffolds for the application of tissue engineering area.

• Journal of the Korean Society of Manufacturing Process Engineers
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• v.18 no.12
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• pp.59-66
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• 2019

In this study, we developed a novel laser sintering deposition system (LSDS) based on solid free-form fabrication (SFF) technology as it has the potential to fabricate complex geometries with controllable architecture for bone tissue engineering applications. The 3D biphasic calcium phosphate (BCP) scaffolds were fabricated with a pore size of 800㎛, a line width and height of 1000㎛, and an overall size of 8.2×8.2×8.0 mm3 according to the design of experiment (DOE) results. Additionally, an optimized manufacturing process using response surface analysis was established to fabricate 3D BCP scaffolds. The fabricated 3D BCP scaffolds were sintered at 950℃, 1050℃, 1150℃, and 1250℃ according to sintering processes with a furnace. As the sintering temperature increased, the porosity increased. Through the compressive strength test, the 3D BCP scaffolds sintered at 1050℃ presented good results of about 0.76 MPa. These results suggest that fabrication methods for 3D bioceramic scaffolds using LSDS may meet the basic requirements for bone tissue engineering.