Delivery of Osteogenic Regulatory Growth Factors - Engineered Bone: Tissue Engineering Intelligence Unit - page 117

Many reviews have been written in this field. 26,107 As a matter of convenience, we will
essentially focus on biodegradable or bioerodible polymers that seem the most convenient for
our purpose.
A great number of parameters will contribute to the rate of degradation:
• water permeability which determines the rate of hydrolysis and whether bulk or surface

hydrolytic degradation occurs

• chemical composition, molecular weight and additives

• physical dimensions of the device (size, surface-to-volume ratio) as well as its site of im-

plantation

Poly ( α -Hydroxy Acids) PHAs
Among the few polymers which have been recognised as degradable in a mammalian organ-
ism, polymers derived from glycolic acid (PG) and from D- and L- lactic acid (PL) enanti-
omers are presently the most attractive compounds. This is largely due to their biocompatibility
and to their resorbability through natural pathways. This is also related to the fact that copoly-
mers issued from glycolic acid and lactic acid (PLG) polymers are approved by the FDA and are
now commercially available. PLG have been the most widely bioerodible systems for con-
trolled release and have a thirty year history of clinical efficacy and safety as sutures. 108
Lactide and glycolide-based polymers are most commonly synthesised by ring-opening melt
polymerisation of lactide and glycolide using a catalyst. 109,110 However, as residuals of the
polymerization reaction, these additives as well as solvents may lead to adverse tissue responses
during polymer degradation. 111 PLG is a general acronym, which corresponds to a large family
of compounds. It is almost impossible to produce the same member of a family twice because
of batch and statistics dependencies of macromolecular structures. Although this latter remark
is applicable to all polymeric compounds, it appeared more critical in the case of degradable
polymeric materials because degradation and bioresorption characteristics are very much de-
pendent on chain characteristics and solid morphology. 112 The polymers degrade by bulk hy-
drolysis of the ester bonds that result in a decrease in molecular weight. Lactic and glycolic acid
resulting from the hydrolytic cleavage are natural molecules that can be metabolised by endog-
enous systems. The rate of hydrolysis is modulated by crystallinity and hydrophobicity of the
monomer components. Crystalline regions are more resistant to hydrolysis than are amor-
phous regions. 112 In addition, PG is more hydrophilic than PL and its biodegradation is more
rapid: PG is resorbed within 3-6 months as PL is resorbed within 6-36 months in vivo. Thus,
PLG copolymers will biodegrade according to the PL and PG constituents' molar ratio. 113
Unfortunately, PLG copolymers synthesised from monomeric constituents can yield to co-
polymers with various combinations of monomeric sequences: from blocky regions of poly-
mers to orderly and alternating ones. Consequently, devices fashioned from copolymers may
have nonuniform rates of hydrolysis, which therefore impact the diversity of host responses.
Some authors highlighted the fact that inadequately characterised homopolymers or copoly-
mers might contribute to discrepancies of results in spite of apparently similar clinical experi-
mental conditions. 111,112,114 For this reason, numerous researchers emphasised homopolymers
(usually polylactic acid) for designing carrier systems, which should result in a more homoge-
neous and predictable outcome. 111,115
Despite of its known biocompatibility, numerous studies have mentioned the presence of
an adverse host tissue reactions from bulk PHA devices as fixation plates and screws. 116 Histo-
logical examination showed a typical nonspecific foreign-body reaction with abundant giant
cells. Vert explained this phenomenon by a heterogeneous degradation of large size devices, the
rate of degradation being greater inside than at the surface of the device. 117 Consequently, the
entrapped carboxylic moieties accumulate within the centre, accelerating internal degradation
of the device until the central mass breaks the outer layer. This contributes to a decrease in local
pH manifesting as an aseptic sinus. 116 Unlike large sized devices, microspheres less than 300
µ m in diameter undergo a homogeneous degradation of the core being equivalent to that at the