Polycaprolactone-based Scaffolds Fabricated Using Fused Deposition Modelling or Melt Extrusion Techniques for Bone Tissue Engineering - Biointerfaces: Where Material Meets Biology - page 242

9.6.3 Bone Morphogenetic Protein
Rai et al. used fibrin as a carrier matrix for recombinant human (rh) BMP-2
in FDM/ME fabricated PCL-based scaffolds. 65,66 The effects of varied con-
centrations of rhBMP-2 (0, 10, 100, 1000 ng mL 1 ) on osteogenic signals
from canine osteoblasts seeded onto PCL-TCP scaffolds were investigated.
Results indicated that rhBMP-2 enhanced the differentiation function of
canine osteoblasts in a non-dose dependent manner, resulting in acceler-
ated mineralisation, followed by apoptosis of osteoblasts as they underwent
terminal differentiation. 65 The release kinetics of rh-BMP2 from PCL-TCP
scaffolds were investigated next. Either 10 or 20 mgmL 1 of rhBMP-2 was
loaded onto the PCL-TCP scaffold using fibrin glue as a carrier matrix.
Analysis revealed that rhBMP-2 was well dispersed and uniformly distributed
across the PCL-TCP scaffolds but formed large clumps which were sparsely
distributed across the PCL only scaffold. The release profile of rhBMP-2
within the PCL-TCP-fibrin construct was dose dependent; 20 mgmL 1
rhBMP-2 had a triphasic release profile and 10 mgmL 1 rhBMP-2 had a
diphasic release profile. 66 In the case of PCL-fibrin constructs, rhBMP-2
showed a diphasic release profile at both rhBMP-2 concentrations. The
addition of TCP appears to delay rhBMP-2 release and thus PCL-TCP scaf-
folds have the potential to be used as vehicles for the controlled release of
rhBMP-2.
Sawyer et al. 67 utilised collagen-I as carrier matrix for rhBMP-2 within
FDM-fabricated PCL-TCP (80 : 20 wt%) scaffolds. For the experiments, 5 mg
of rhBMP-2 was loaded onto the PCL-TCP-collagen scaffolds prior to either
release assays or the implantation into critical-sized rat calvarial defects
(Figure 9.6a). Release assays over 48 h indicated that rhBMP-2 underwent
initial burst release, reaching 100% release within the first 6 h. Post-
implantation, functional, histological and mechanical analyses clearly
demonstrated that bone healing ecacy of PCL-TCP-collagen-rhBMP-2
implants was greater than PCL-TCP-collagen implants without the inclu-
sion of rhBMP-2. 67 At 15 weeks, PCL-TCP-collagen-rhBMP-2 implants
stimulated significant bone repair, with most defects reaching closure with
full bridging from the calvarial host bone edges, as indicated by the m-CT
images and the stained histological sections (Figure 9.7b and c). For the
PCL-TCP-collagen implants without rhBMP-2, new bone formation was
minimal, growing only from the periphery of the defect. 67
In a similar fashion, Abbah et al. 68 loaded rhBMP-2 (0.6 mg per scaffold)
onto collagen-coated PCL-TCP (80 : 20 wt%) scaffolds and subsequently
analysed these in an anterior-lumbar spinal pig model (Figure 9.7a) to
evaluate their function as a biological interbody cage device for bone re-
generation and spinal fusion. Histological and m-CT analyses indicated that
after 3 months the rhBMP-2 loaded scaffolds induced notable new bone
formation with complete defect bridging (Figure 9.7c and d). At 6 months,
advanced bone maturation was indicated with increased amounts of hori-
zontal trabeculae interlacing with the columns of vertical trabeculae. 68 Graft

d n 3 r 4 n g | 1

.