Delivery of Osteogenic Regulatory Growth Factors - Engineered Bone: Tissue Engineering Intelligence Unit - page 113

Table 1. Major classes of materials used as carriers for the delivery of osteogenic
growth factors

S e l e c t e d

C a r r i e r A d v a n t a g e s D r a w b a c k s M o d e l R e f e r e n c e s

O r g a n i c c a r r i e r s • Biocompatible • Potential Non union 91,144

• Biodegradable pathogen fracture defects

DBM/Collagen/Gelatin • Functionalizable transmission Long bone defects 9,84

Fibrin glue • Moldable Dental/maxillofacial 85,88,

Hyaluronic acid • Natural subtratum defects 101,146

Chitosan for cells Spinal fusion 12,15,89

I n o r g a n i c c a r r i e r s • Biocompatible • Brittle Non union fracture -

Tricalcium phosphate • Osteoconductive • Difficult to mold defects

Hydroxyapatite • Structurally rigid Long bone defects 61,62,147

Coral Dental/maxillofacial 63,148

Ceramic glass defects

Spinal fusion 13

S y n t h e t i c p o l y m e r s • Ease to • Additives may Non union fracture 149

manufacture lead to adverse defects

Poly( α -hydroxy acids) • Cost efficient tissue responses Long bone defects

Polyanhydrides • Free of • Break-down Dental/maxillofacial

Poloxamers contamination products may defects

Methacrylate-derived • Ease to sterilize lead to Spinal fusion

polymers • Functionalizable inflammatory

reaction

carrier. 49 Highly porous HAP has a larger surface area enabling an increased amount of BMP
to be entrapped throughout the scaffold. A comparison among porous blocks of HAP with
different pore sizes demonstrated that pores sizes of 300-400 µ m most favours bone forma-
tion. 50 In honeycomb-shaped hydroxyapatite with straight tunnel structures of various diam-
eters, tunnels with smaller diameters (90-120 µ m) induced cartilage followed by bone forma-
tion, whereas those with larger diameters (350 µ m) induced bone formation directly within
the tunnels. 51 In the rat ectopic assay, significant bone induction was observed when osteogenin
(i.e., BMP-3) was combined with a disc-shaped HAP carrier, but no osteogenesis was observed
when the same factor was combined with HAP in the form of granules. 24 More recently, Jin et
al have shown that the geometry of HAP clearly controlled vascular capillary invasion and
modulated cell growth and differentiation. 23 The main geometrical factors involved in initiat-
ing rapid osteogenesis are the porosity and its interconnectivity within the implant, which give
rise to easy access of oxygen-carrying capillaries.
However, HAP is rigid, brittle and difficult to shape. This limits its use as a bone substitute.
On the contrary, tricalcium phosphates can be prepared in a paste form that can be moulded to
a desired shape prior to setting. In 1984, Urist et al reported that a composite made of bovine
BMP and β -TCP produced 12 times more bone than BMP alone in a rodent assay system. 47
When implanted in adult dogs with skull defects of critical size, this composite induced an
almost complete repair of the defect (91%-100%) by deposits of new bone. 52 However, the use
of Tricalcium phosphates in repairing skeletal defects has not proven satisfactory because of
their too rapid rate of resorption which is not always commensurate to bone formation. 41
Indeed, the TCP absorptive rate in vivo was 60-80% in 6 months, whereas HAP is poorly
degraded in vivo (several µ m thick after 18 months). 53-57