Bone tissue engineering scaffolding: computer-aided scaffolding techniques

Abstract

Tissue engineering is essentially a technique for imitating nature. Natural tissues consist of three components: cells, signalling systems (e.g. growth factors) and extracellular matrix (ECM). The ECM forms a scaffold for its cells. Hence, the engineered tissue construct is an artificial scaffold populated with living cells and signalling molecules. A huge effort has been invested in bone tissue engineering, in which a highly porous scaffold plays a critical role in guiding bone and vascular tissue growth and regeneration in three dimensions. In the last two decades, numerous scaffolding techniques have been developed to fabricate highly interconnective, porous scaffolds for bone tissue engineering applications. This review provides an update on the progress of foaming technology of biomaterials, with a special attention being focused on computer-aided manufacturing (Andrade et al. 2002) techniques. This article starts with a brief introduction of tissue engineering (Bone tissue engineering and scaffolds) and scaffolding materials (Biomaterials used in bone tissue engineering). After a brief reviews on conventional scaffolding techniques (Conventional scaffolding techniques), a number of CAM techniques are reviewed in great detail. For each technique, the structure and mechanical integrity of fabricated scaffolds are discussed in detail. Finally, the advantaged and disadvantage of these techniques are compared (Comparison of scaffolding techniques) and summarised (Summary).

Keywords: Bioceramics; Bone tissue engineering; Computer-aided scaffolding techniques; Scaffold; Solid free-form fabrication.

Fig. 1

Sequence of interfacial reactions involved in forming a bond between bone and bioactive ceramics and glasses (O’Donnell ; Jones ; Gerhardt and Boccaccini 2010)

Fig. 2

Schematic presentation of commonly used techniques for scaffold fabrication: a solvent casting/particulate leaching; b freeze-drying; c TIPS; d gas foaming and supercritical fluid processing; and e electrospinning (Puppi et al. 2010)

Fig. 3

Flowchart of the powder sintering method to produce a porous ceramic scaffold (Chen 2011)

Fig. 4

Flowchart of fabrication of ceramic or glass foams via polymer foam replication (Chen 2011)

Fig. 5

Flowchart of the production of bioactive glass foams using sol–gel process (Chen 2011)

Fig. 6

Typical pore morphologies of porous scaffolds by various techniques: a solvent casting/particulate leaching (Dalton et al. 2009); b freeze-drying (Morsi et al. 2008); c TIPS (Dalton et al. 2009); d gas foaming (Morsi et al. 2008); e electrospinning (Dalton et al. 2009); f replication technique (Chen et al. 2008); g sol–gel technique (Sepulveda et al. 2002)

Fig. 7

The designed scaffold unit cells based on different feature primitives (Sun et al. 2007)

Fig. 8

Cross-sectional structure viewed in the X–Z plane and direction of the FDM-build part (Zein et al. 2002)

Fig. 9

Flowchart presenting typical CAM technology (Leong et al. 2003)

Fig. 10

Schematic representation of an SLA system (Chu ; Bartolo et al. ; Hopkinson and Dickens 2006)

Fig. 11

Images of PDLLA scaffolds built by SLA. a Photograph; and b SEM micrograph (scale bars represent 500 μm) (Melchels et al. 2009)

Fig. 12

Examples of bioceramics scaffolds built by advanced SLA: structures prepared from a HA and TCP using μSLA system (Seol et al. 2013); b methacrylated oligolactones using a TPP system (Weiss et al. 2011); and c 45S5 Bioglass^® using DLP system (Tesavibul et al. 2012)

Fig. 13

Schematic representation of the SLS system (Chu ; Bartolo et al. ; Hopkinson and Dickens 2006)

Fig. 14

Images of PHBV/TCP composite scaffolds built by SLS: a photograph; and b SEM morphology (Duan et al. 2010)

Fig. 15

Schematic representation of the 3DP system (Fielding et al. 2012)

Fig. 16

A scaffold with two distinct regions: 90 % porous _D,L-PLGA/_L-PLA as the cartilage region (upper side) and 55 % porous cloverleaf-shaped _L-PLGA/TCP as the bone region (lower side) (Sherwood et al. 2002)

Fig. 17

Examples of bioceramic scaffolds produced by 3DP: a TCP and HA photograph; b SEM image of TCP; and c SEM image of HA (Warnke et al. 2010). The magnifications of b and c are the same

Fig. 18

Schematic representation of the FDM system (Zein et al. 2002)

Fig. 19

SEM images of PCL/TCP composite scaffolds obtained from FDM: a structure of top view with inset of cross-sectional view; and b osteoblast cells attached on the scaffold surface (Zhou et al. 2007)

Fig. 20

Schematic representation of MHDS (Kim and Cho 2009)

Fig. 21

SEM images of PCL/PLGA scaffold fabricated via MHDS (Lee et al. 2012)

Fig. 22

Schematic representation of LDM (Xiong et al. 2002)

Fig. 23

Images of a PLLA/TCP composite scaffold made in LDM process, SEM images of the cross-section of the scaffold; b low magnified; c high magnified (Xiong et al. 2002); d multi-material (PLGA/collagen) scaffold made in M-LDM process; and e SEM images of the interface of the scaffold (Liu et al. 2009)

Fig. 24

Schematic representation of PED (Wang et al. 2004)

Fig. 25

SEM images of a PCL scaffold fabricated via PED; b low magnified; and c high magnified (Shor et al. 2009)

Fig. 26

Schematic representation of PAM (Vozzi et al. 2002)

Fig. 27

Light microscopy of the PAM-printed PLLA/CNT composite scaffolds (Vozzi et al. 2013)

Fig. 28

Schematic representation of robocasting (Martínez-Vázquez et al. 2010)

Fig. 29

SEM images of a surface view of a glass (6P53B) scaffold with a gradient pore size; and b cross sections of the scaffold (Fu et al. 2011)

Fig. 30

Schematic representation of 3D-Bioplotter^® (Landers et al. ; Gurr and Mülhaupt 2012)

Fig. 31

SEM micrographs of a a scaffold obtained with the 3D-Bioplotter^® technology; b cross-sectional view of the scaffold; and c the surface morphology (Oliveira et al. 2010)

Fig. 32

3D scaffolds manufactured by various SFF techniques: a SLA; b SLS; c 3DP; and d FDM (Dalton et al. 2009)