Polycaprolactone-based Scaffolds Fabricated Using Fused Deposition Modelling or Melt Extrusion Techniques for Bone Tissue Engineering - Biointerfaces: Where Material Meets Biology - page 246

defects. Results have shown that interconnected pores and large pore sur-
face area enhanced bone regeneration regardless of pore geometry. Fur-
thermore, sequential deliveries of BMP-2 followed by BMP-7 further
enhanced in vivo bone regeneration. 73
It is clear that FDM/ME PCL scaffolds can be an effective, localised carrier
for BMPs into defect sites promoting bone regeneration whilst preventing
ectopic bone formation which may result from high burst release and con-
comitant high physiological doses of BMPs.

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9.7 Advanced Scaffold Architecture

9.7.1 Scaffolds with Vascular Channels
Neovascularisation plays a major role in bone regeneration. During a normal
bone repair process, the formation of granulation tissue is very important.
This granulation tissue is a collection of small blood vessels and fibrous
tissue providing structure and the delivery of nutrients. This plays a key role
in the reparative phase where progenitor cells migrate into the injury site
and differentiate. The design of scaffolds for bone TE is driven towards the
generation of bioactive constructs which can stimulate vascularisation and
subsequent guidance of vasculature. In a recent study, Muller et al. 74 fabri-
cated a PCL-HA (90 : 10 wt%) scaffold with a patient-specific vessel network
(Figure 9.9a) by combining a RP approach with CT data and CAD technology.
The scaffolds were seeded with bone marrow-derived mesenchymal stem
cells and implanted into a rat groin model (Figure 9.9c). After 3 weeks,
scaffolds were explanted (Figure 9.9d) either for histological analysis
(Figure 9.9f-h) or transferred via microsurgery as composite tissue-
polymer-free flap constructs onto the neck of the rats (Figure 9.9e). Histo-
logical analyses indicated neovascularisation through the customised
channels within the scaffold. 74 Following the transfer of prefabricated
composite tissue-polymer-free flaps to the neck, the flaps were observed to
be viable due to the good perfusion and capillary refill from the induced
vascular network.
A novel bobbin-shaped poly( L -lactide-co- DL -lactide) (PLDLLA)-PCL-TCP
scaffold was mentioned previously as an example of a PCL scaffold
(Figure 9.2c). Hyaluronan gel was used as a carrier matrix for cells or rhBMP-
2 and an arterio-venous (A-V) loop placed around the scaffold to support
axial vascularisation. 75 The A-V loop was created from a 20 mm vein graft
harvested from the right femoral vein of a rat. In vitro studies showed that
rhBMP-2 was gradually released from the gel for up to 35 days and some
rhBMP-2 was retained inside the gel. Osteoblasts indicated good viability
within the gel. 75 PLDLLA-PCL-TCP scaffolds loaded with hyaluronan
hydrogels containing rhBMP-2 (either 500 ng mL 1 or 2.5 mgmL 1 ), or
3million osteoblasts were implanted into Lewis rats for 8 weeks. 75 Scaffolds
with a plain hydrogel served as controls. The gradual degradation of hya-
luronan gel and thus the gradual released of rhBMP-2 induced bone-related

.