Interdisciplinary Neurosurgery 13 (2018) 59–65

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Interdisciplinary Neurosurgery
journal homepage: www.elsevier.com/locate/inat

Technical Notes & Surgical Techniques

Paediatric cranioplasty: A review T

a b a,⁎
Anooja Abdul Salam , Imogen Ibbett , Nova Thani
a
Department of Neurosurgery, Royal Hobart Hospital, 48 Liverpool Street, Hobart, Tasmania 7000, Australia
b
Royal Hobart Hospital, 48 Liverpool Street, Hobart, Tasmania 7000, Australia

A R T I C LE I N FO A B S T R A C T

Keywords: Objective: This study reviews the current literature for the optimal material to use in paediatric cranioplasty
Paediatric cranioplasty surgeries.
Complications Materials and methods: A search of Medline (Ovid)/PubMed/Scopus was undertaken to assess the current
Biomaterials methods in use for the reconstruction of cranial defects in paediatric patients.
Autologous
The search terms used were: cranioplasty”, calvarial reconstruction”, “cranial defect, “allograft”, “bioma-
terial”, “methyl methacrylate,” “titanium,” “hydroxyapatite,” all in association with “paediatric,” “adolescent,”
or “infant.” Articles were limited to materials published from 2005 onwards.
Results: The above search identified 7104 papers relating to paediatric cranioplasty published after 2005, of
which 7070 did not meet inclusion criteria. The remaining 34 papers were included in this review.
Conclusion: An ideal material for cranioplasty, especially in the paediatric age group, has not been established
based on the available evidence. The current trend in practice appears to be the use of particulate bone grafts or
exchange cranioplasty in infants. In older children, custom made implants using titanium or hydroxyapatite have
been used successfully.

1. Introduction
Cranioplasty is an integral aspect in surgery involving cranial vault
tumours, infection, trauma or congenital defects [1]. Reconstruction of
the integrity of the calvarium protects the underlying brain, improves
cosmesis [2] and importantly promotes the establishment of a homeo-
static environment for the autoregulation of cerebral blood flow [3].
Characteristics of the paediatric population differ from adults due to
variance in anatomy and the effect of growth of the skull [4].
The cranial vault grows by deposition of bone perpendicular to the
sutures, namely intramembranous ossification [5]. Fig. 1 summarises
the stages of suture morphogenesis and fusion [6]. Moulding takes
place by absorption of the inner layer and osteoblast-mediated thick-
ening of the outer layer [5]. At birth the bones of the vault are solid. In
adulthood, vascular channels develop with cancellous bone matrix
forming the diploe, thus developing inner and outer table. Parts without
diploe, namely squamous temporal bone, parietal bone, foramen
magnum, skull base, cribriform plate and orbital roof, are prone to
fracture [7].
Hence, a material that does not allow bony ingrowth has increased
risk of failure because of the peculiar growth of the immature skull,
with prevalent deposition of bone at the outer layer and resorption of
bone at the inner layer as described above [8].
In the paediatric population, an ideal cranioplasty material should
integrate to the adjacent bone with the ability to ‘grow’ with the child's
calvarial growth. Other desirable properties would include availability,
cost effectiveness, light-weight, nonmagnetic, radiolucent, sterilisable,
and easily secured to the calvarium [3]. The aim is to select the safest
material with fewest complications thus resulting in less morbidity and
a higher success rate, but being cost effective at the same time [3].
Materials used for cranioplasty can be categorised into three main
groups: organic, synthetic-organic, and inorganic [9].
Organic cranioplasty materials include autograft (harvested from
the same individual), allograft (bone graft from another individual),
and xenograft (taken from another species) [9] We have summarised
below the materials used in paediatric cranioplasty and reported com-
plications seconday to its use (see Table 1).
Synthetic-organic materials (“biomaterials”) are manufactured nat-
ural bone minerals or proteins found in the human body. Examples
include hydroxyapatite and bone morphogenic protein [9]. Autologous
bone and biomaterials are the two major sources for cranial re-
construction in adults and children [10].

Abbreviations: PMMA, polymethylmethacrylate cranioplasty; HA, hydroxyapatite; BMP, bone morphogenetic protein; ADSCs, adipose-derived stem cells; CSF, cerebrospinal fluid; CBS,
Custom Bone Service
⁎
Corresponding author.
E-mail address: novathani@gmail.com (N. Thani).

https://doi.org/10.1016/j.inat.2018.03.004
Received 18 October 2017; Received in revised form 17 January 2018; Accepted 4 March 2018
2214-7519/ © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).
A.A. Salam et al.
Fig. 1. Stages of suture morphogenesis and fusion [6].
[The figure above is taken and modified from Opperman, L. A. (2000).]
Inorganic substances do not have biological activity. These include
methyl methacrylate, silicone, porous polyethylene, titanium mesh, and
bioactive glass [9].
While there are various studies to support the use of biomaterials in
adult cranioplasty, it is very limited in paediatrics. The use of bioma-
terials as a substrate for cranioplasty rather than autologous bone is
controversial in paediatrics due to the potential harmful effects caused
by a non-flexible, foreign material on normal cranial growth, in-
tracranial migration of biomaterial, higher incidence of infection, in-
flammatory tissue reaction and material disintegration or fracture [2].
1.1. Materials and methods
A search of Medline (Ovid)/ PubMed/Scopus was undertaken to
assess the current methods in use for the reconstruction of cranial de-
fects in paediatric patients.
The search terms used were: cranioplasty”, calvarial reconstruc-
tion”, “cranial defect, “allograft”, “biomaterial”, “methyl methacry-
late,” “titanium,” “hydroxyapatite,” all in association with “paediatric,”
“adolescent,” or “infant.” Articles were limited to materials published
from 2005 onwards.
All titles and abstracts were reviewed to identify eligible papers. The
reference sections of included studies were also searched to identify any
omitted studies.
Inclusion criteria were: publication since 2005, patients aged < 18
years and articles specifying cranioplasty material used. Data extracted
included type of cranioplasty, number of patients, patient age, follow
up data, and complications requiring second cranioplasty procedure.
1.2. Results
The above search identified 7104 papers relating to paediatric
cranioplasty published after 2005, of which 7070 did not meet inclu-
sion criteria. The remaining 34 papers were included in this review.
In this paper we will discuss the preferred materials used in
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Interdisciplinary Neurosurgery 13 (2018) 59–65
paediatric cranioplasty, including their advantages and disadvantages,
as per the data obtained from our literature search.
2. Autologous cranioplasty
In the paediatric population, as in the adult population, autologous
cranioplasty is considered the gold standard. Hence, when available
and appropriate, this is the commonest technique used [9]. The most
common donor areas for autologous bone are the cranium, ribs and iliac
crest [9].
The advantages of using autologous bone include decreased infec-
tion risk and minimal dislodgement or disintegration due to higher rate
of revascularisation and integration with adjacent bone [9,10]. Auto-
logous also means that there are no issues with host rejection and tends
to merge well with the cranial cavity, resulting in lower risk of fracture
[11].
One of the main disadvantages in paediatric age group is availability
of autologous bone. Moreover, harvesting autologous bone involves
prolonged operative time, donor site pain and infection, graft resorp-
tion and difficulty moulding to the defect. Often, and in particular with
the paediatric population, the graftable tissue is insufficient to cover the
defect [9]. For example, in paediatric patients with traumatic brain
injury requiring decompressive craniectomy, cranioplasty can be a
challenge due to the large residual defect requiring a large graft [4].
Martin et al. [4] reported on the long-term outcomes after re-
placement of the autologous bone flap over a 13 year period. In their
study, the incidence of resorption of the bone flap was higher in chil-
dren under eight years (81.8%) compared to older children (42%). Even
though a preserved autologous bone flap is an attractive option for
paediatric cranioplasty, the increased rate of resorption requiring sec-
ondary cranioplasty, particularly in patients under eight years, suggests
this technique should be used preferably in older children [4,12].
Synthetic cranioplasty should be considered for children below eight
years of age [4].
 A.A. Salam et al.

Table 1
Summary of paediatric cranioplasty materials and reported complications between the years 2005 to 2016.
Author (year) Cranioplasty material used No of pts Age range (mean) Follow up (mean) Complications requiring second cranioplasty Comments

David et al. (2005) [25] HA cement 8 25 m–100 m (55 m) 23 m–72 m (55 m) 0% Small sample
?validity
Pang et al. (2005) [14] HA cement + bioresorbable plates 15 2 y–9.5 y (5.5 y) 2.2 y–4.2 y (2.9 y) 0%
Greene et al. (2008) [17] Particulate cranial graft 38 3–20 y (8 y) 0.5 y–18 y (6.5 y) 3% (1 graft resorption)
Gosain et al. (2009) [20] Bioactive glass 3 3–5 y (4.3 y) 1 y–3 y (2.1 y) 0% Small sample
Gosain et al. (2009) [20] Demineralised bone matrix 8 3–5 y (4.3 y) 1 y–3 y (2.1 y) 33% (1 inadequate fill of defect)
Gosain et al. (2009) [20] Prefabricated polyethylene (Medpore ®) 3 3–5 y (4.3 y) 1 y–3 y (2.1 y) 0% Small sample
Biskup et al. (2010) [26] HA cement 23 6.5 m–14 y 9 m–19 m (12.7 m) 0%
Singh et al. (2010) [27] HA cement 78 23 m–18 y (9 y) 1 y–7 y (not stated) 0%
Gao et al. (2010) [18] Autologous cranial particulate graft 53 3.3–78.6 months(20.2 m) 25.7 months 5.3%

61
Rogers et al. (2011) [19]
Wong et al. (2011) [28]
Frassanito et al. (2012) [29]
Lin et al. (2012) [30]
Pierdra et al. (2012) [31]
Bowers et al. (2013) [12]
Stefini et al. (2013) [21]
Martin et al. (2014) [4]
Martin et al. (2014) [4]
Vercler et al.(2014) [13]
Piitulainen et al. (2015) [15]
Frassanito et al. (2015) [8]
Park et al.(2016) [3]
William et al.(2016) [2]
Fiaschi et al.(2016) [24]
Exchange calvarial graft 20 9.2 m–22.3 y (8.3 y) 24 w–3.7 y (mean 1.57 y) 0%
HA cement 4 4.9 y–15.2 y (11.75 y) 37.5 m–90 m (50.83 m) 75% (3 infection)
Frozen bone flap 3 1 m–11 m (6 m) Not stated 100% (3 resorption) Small sample
Porous polyethylene 9 2.4–15 y (6.8 y) 0.5 m–22.4 m (3.6 m) 0%
Frozen bone flap 61 not stated (9.3 y) 24 m (2–124 m) 36% (18 resorption, 4 infection)
Frozen bone flap 54 Not stated (6.2 y) 37.9 m (1.5 m–168 m) 50% (27 resorption, 9 infection) < 2.5 years increased resorption noted
Custom made hydroxyapatite implant 114 7–14 y (not stated) Not stated 0% 5% late complication reported
Bone flap 23 1 m–17 y (13.3 y) 21 m–155 m (81.3 m) 43% (8 resorption, 2 infection)
PMMA 4 13–17 y (15.75 y) 79 m–125 m (102.7 m) 0% Only looked at older age groups
Split cranial graft 418 58 days–3 y(400 d) 1y 3.1% Persistent cranial defect
Fibre-reinforced composite bioactive glass 7 2.5–16 (10.4 y) 22 m–53 m (35.1 m) 29% (2 infection) High infection rate
Custom bone service implant(macroporous HA) 23 < 7 y (2.5–6 y) 1 y (13-80 m) 20.8% Nil complication after 6 m
Custom made titanium implant 7 8–17 y 6–24 m (14.1 m) 0% Not looked at ages less than eight years
Custom made titanium implant 22 < 18 y (12.9 y) 4.6 y 0%
Custom PMMA 12 5 m–12.5 y (84.33 m) 55.7 m 0% 3patients- minor complication
Interdisciplinary Neurosurgery 13 (2018) 59–65
A.A. Salam et al.
2.1. Split calvarial graft
Cranial bone is a triadic structure made of a mouldable inner and
outer cortex separated by an intervening diploic space [13]. The diploic
space has soft cancellous bone that allows splitting of the cranium into
separate bone fragments of similar size, shape, and contour [13]. These
bone fragments double the amount of autologous bone grafts available
and can be used in the reconstruction of the cranial vault [13].
Autologous split calvarial graft is the material of choice when
available, being the bone of same origin, volume of material available,
single operative site, pliability and favourable rounded contour [14].
Unfortunately there are limited donor site options for younger children
[10]. The most commonly used donor sites are calvarium, ribs or iliac
crest [15]. Harvesting of iliac crest is contraindicated below nine years,
as it interferes with growth, thus leaving only calvarium and rib graft as
the viable option for younger children [10]. There is no minimum pa-
tient age associated with using rib grafts in children for cranial re-
construction [14]. However, rib grafts are unsuitable for some cranial
defects due to the stiff grid formation by parallel ribs, increased post-
operative morbidity due to long surgical time and need for a second
operative site [14]. Combining the above materials, “catcher's mask”
cranioplasty was performed by Takumi & Akimoto [16]. They used rib
grafts as a supportive base for split calvarial grafts in three children
[14]. This helped to shape the forehead while reducing the risk of graft
resorption [16]. None of the subjects were reported to have sunken flap
syndrome or infection [16].
There is a school of thought that in children below seven years of
age, harvesting a split calvarial graft is difficult due to poor differ-
entiation of the diploic bone [14]. Especially for children less than three
years, it is not recommended due to skull thickness and underdeveloped
diploe [14]. However, according to Vercler et al. [13], the cranium of
children younger than 3 years can be safely used for split calvarial
grafting because it provides a stable immediate coverage. Vercler et al
[13] did a retrospective study of 418 children with craniosynostosis
under three years of age and successfully performed split calvarial
grafting, out of which only 13 children required revision cranioplasty at
the region of reconstruction (3.1% complication). They used a 2 mm
straight osteotome initially to separate the cortices of the cut bone edge,
which was later switched to a wider osteotome until the cortices were
separated [13]. The authors claim to be almost always successful in
finding a clear plane between inner and outer cortex even among the
youngest children treated, unless the child has a condition named la-
cunar skull deformity, which is comprised of an incomplete ossification
of the skull [13]. Thus they concluded that the cranium of children
between two months and three years of age can be safely split between
inner and outer cortex to obtain split cranial graft [13].
In conclusion the advantages of split calvarial graft are similar to
that of autogenous graft with added advantage of having more graft
material, ability to use single operative site, good pliability and also
availability of graft material with a favourable rounded contour.
The main disadvantage with split calvarial graft is the limited donor
site options for younger children. However, the studies described ear-
lier supporting the use of split calvarial graft in children as young as
2 months old is quite promising.
2.2. Particulate calvarial cranioplasty
Particulate bone graft consists of small particles of autologous cor-
ticocancellous bone and hematopoietic and mesenchymal marrow [9].
Particulate calvarial bone graft can be harvested either from the ecto-
cortex or the endocortex of a full thickness bone segment of the cal-
varium [17]. Tiny pieces of bone are harvested with a low-speed, hand-
driven bit and brace to obtain the particulate bone graft [17].Particu-
late graft retains osteogenic, osteoinductive, and osteoconductive po-
tential, readily vascularizes and is easily transformed to fit the defect
because of its corticocancellous particulate architecture, and maintains
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Interdisciplinary Neurosurgery 13 (2018) 59–65
better volume because of its cortical component [17]. Most im-
portantly, a developed diploic space is not required for the harvest of
particulate grafts thus making it an ideal material for infants and
younger children [17].
Cranial expansion surgery can result in exposed dura and cranial
defects in children [18]. It has been found that the use of particulate
bone graft reduces the occurrence of residual bony defects when used
for primary closure in cranial expansion [17]. Inlay particulate bone
graft is effective for covering cranial defects in children but needs to be
used in areas where the dura is at level with the surrounding bone due
to lack of structural support provided by the graft [18]. Gao et al.
looked at 53 children who underwent cranial expansion surgeries.
26.7% of children without primary graft required secondary cranio-
plasty, compared to 5.3% in children undergoing primary particulate
cranioplasty. This study suggests that primary cranial particulate bone
grafting remarkably reduces the need for secondary cranioplasty [18].
The disadvantage with particulate bone graft is that it is not ideal to use
alone in areas where smooth contouring is required or in regions of
dural scarring or recession since it does not provide structural support
or contour [19].
2.3. Exchange cranioplasty
Exchange cranioplasty is a type of autologous cranioplasty where
full-thickness structural bone graft is harvested from a comparatively
normal area of the skull to repair the osseous defect [19]. The donor site
is subsequently covered with particulate bone graft obtained from the
endocortex of the structural graft or ectocortex of the intact cranium
[19].
Exchange cranioplasty requires no additional donor site and can be
used to repair large cranial defects which would be almost impossible to
achieve with split calvarial or rib graft [19]. It is effective for all age
groups including very young children where diploic space has not de-
veloped [19]. A corticocancellous graft can be used in areas where
structure and shape is required and the graft forms a diploic space
which grows as thick as the surrounding bone, enabling it to be used as
donor site for subsequent procedures if needed [19]. It is economical
and the graft is readily available meaning it can be performed anywhere
in the world [19].
Thus the disadvantages of just using particulate bone graft are
overcome by exchange cranioplasty as reported in the study by Rogers
et al. [19] They studied 20 patients between the ages of 9.2 months to
22.3 years and followed up for 3.7 years. They reported that exchange
cranioplasty is very effective for closing large cranial defects in all age
groups [19].
Exchange cranioplasty has all of the advantages of autologous
grafting without the limitations as described below:
1.) No additional donor-site incision or morbidity needed for this
method,
2.) Particulate bone harvest yields large quantities of bone,
3.) It is highly effective at any age since corticocancellous particulate
bone graft can be obtained, from patients in whom a diploic space
has not developed yet,
4.) The defects created in the endocortical or ectocortical surfaces heal
completely and donor bone returns to its preoperative form [19].
3. Synthetic-organic cranioplasty
3.1. Biomaterials/synthetic-organic materials in cranioplasty
Biomaterials are manufactured natural bone minerals or proteins
found in the human [9].The main advantages of using biomaterial are
unlimited availability, no donor site morbidity, biocompatibility, and
reduced operating time due to ease of use [20].Biomaterials such as
bioactive glass and demineralized bone have osteoconductive capacity
A.A. Salam et al.
and are replaced by bone in the long run by recruiting osteoblasts from
the nearby skeleton [20].
Prefabricated polymers are another type of biomaterial which have
a very low resorption rate and permit vascular and soft-tissue ingrowth
after a week, and bony ingrowth after three weeks [20]. Examples in-
clude porous polyethylene and hard-tissue replacement polymer [20].
Gosain et al. [20] reviewed three different biomaterials over a
period of 11 years and developed an algorithm based on three factors:
completion of skeletal growth; whether inlay or on lay construction is
required; and the function of area of reconstruction. The biomaterials
used in the study consisted of three classes: cement pastes, including
hydroxyapatite and calcium phosphate bone cement; biomaterials de-
signed to be replaced by bone, which included bioactive glass and de-
mineralised bone matrix; and prefabricated polymers. The study in-
cluded 25 patients with a mean age of 5.5 years and a mean follow up of
3.3 years [20].
The authors made the following recommendations:
• cement paste or prefabricated polymers for on lay or inlay re-
construction after > 90% skeletal growth is complete (above three
years) for cranial vault
• biomaterials designed to be replaced by bone are ideal for inlay
reconstruction
• autologous bone grafting or delayed reconstruction should be con-
sidered when on-lay reconstruction is required during active skeletal
growth [20].
The number of patients in this study is small and hence the re-
commendations here could be used as a base for future studies to
evaluate the outcomes of using biomaterials in paediatric populations
in a larger sample size.
3.2. Hydroxyapatite cranioplasty
Hydroxyapatite is a calcium phosphate and constitutes around 60%
of human bone [11,21]. It can be produced synthetically as a ceramic
and is reinforced with titanium mesh to obtain more implant strength
[11]. It is easily moulded and does not create artefact on imaging [11].
It promotes new bone formation on the implant surface due its similar
composition to bone, and propensity to accumulate calcium and
phosphate ions [21].
The advantages of hydroxyapatite use in children are, it allows
expansion of the growing cranium, has acceptable chemical bonding
with bone, produces minimal inflammation and gives very good cos-
metic results since it can be shaped as required [11].
The disadvantages of hydroxyapatite and other calcium-based bone
cements are they can disintegrate or fragment, are easily displaced or
fractured, do not integrate with the bone and have higher infection
rates [18].
Pang et al. [14] combined hydroxyapatite with an underlying macro
pore perforated plate in 15 children. The aim was to reduce cracking of
the implant from CSF pulsation pressure through the dura [14]. They
did not report any complication of implant fracture, infection or revi-
sion cranioplasty [14]. Although the sample size is low, the results from
this study are promising and a larger study looking at the long-term
outcomes of this method would be useful.
Stefani et al. [21] used custom-made porous hydroxyapatite im-
plants which have a very high permeability. They looked at 114 pae-
diatric patients aged seven to 14 years. They reported no early fracture
or infection and only 5% late, post-traumatic fracture [21].
The Custom Bone Service (CBS) is a customized bioceramic implant
constituted of macroporous hydroxyapatite [8]. This implant is ex-
pected to provide a steady decrease of complication after osteointe-
gration, by attaining the same features of the skull bone [8].
In the study conducted by Frassanito et al., 23 children aged < 7
year were treated with custom made porous hydroxyapatite devices
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Interdisciplinary Neurosurgery 13 (2018) 59–65
with failure rate of 20.8% requiring secondary cranioplasty in the first
6 months. However, CBS may be considered as a valid option for cranial
repair in children under 7 years old, as the failure rate is comparatively
lower than other materials currently in use [8].
4. Synthetic cranioplasty
4.1. Titanium cranioplasty
Titanium is a non-corrosive, biocompatible, relatively radiolucent
metallic alloy with high tensile strength and pliability with compara-
tively low inflammatory reactions [3,11]. It is also found to have the
lowest incidence of infection compared to all other cranioplasty mate-
rials [22]. It can be used along with other cranioplasty materials to
increase the strength of the implant [11].
There is no risk of resorption with titanium since it is biologically
inert, thus improving the long-term outcome for those undergoing
custom made titanium cranioplasty as demonstrated by the study done
by Park et al. and William et al. [3].
The aim of the study was to demonstrate the efficiency of custom
made 3D printed titanium implants; there were no complications (0%)
in the 22 patients aged < 18 years studied by William et al. and also for
the 7 patients aged 8-17 years followed up by Park et al. [3].
Custom made titanium implants are one of the latest modalities
used, especially in paediatric cranioplasty. These patient-specific,
tailor-made titanium implants have very good anatomic alignment thus
providing excellent cosmetic results [3]. It is comparatively easier to
undertake the procedure with custom made implants, because they fit
perfectly thereby reducing the operative time and lowering infection
risk [3]. Park et al. used custom-made implants with a honeycomb
structure which made the implants light weight and compact, reducing
the materials required and thus minimising the overall cost [3]. This
particular design helps in tissue integration, thereby reducing tissue
inflammation or infection, and facilitates bone ingrowth reducing the
need for revision cranioplasty [3].
However, the major disadvantage in using titanium implant is the
increased upfront cost of utilizing the material [23].
4.2. Polymethylmethacrylate (PMMA) cranioplasty
Polymethylmethacrylate is the second material of choice after au-
tologous cranioplasty in adults. Main advantages include its ready
availability and also it is a low cost polymer with good strength and
biocompatibility profiles similar to that of bone [23].
Polymethylmethacrylate (acrylic) is not used in paediatric age
groups, mainly because of the exothermic reaction which occurs during
its setting, which can be harmful to the underlying brain tissue [14]. It
has the potential to cause effusions secondary to tissue inflammation
and does not integrate with the growing bone [14]. Other dis-
advantages, including its brittle nature and lack of any osseointegra-
tion, prevents it from being suitable to use for permanent cranioplasty
in the growing skull and is at risk for fracture and separation [23].
However, Martin et al. [4] performed cranioplasty using PMMA in four
children between the ages of 13 to 17 years and followed up for an
average 102 months with nil complications post operatively.
It has been found that the use of customized PMMA avoids the
exothermic reaction of mouldable PMMA described earlier and hence is
a better option [24].This has been proven by a retrospective study
conducted by Fiaschi et al. for twelve children < 12 years of age who
underwent customized PMMA cranioplasty [24]. The advantages of the
custom-made technique are having a well-fitting implant, preventing
exposure of brain tissue to the exothermic reaction, no monomer re-
sidue or dust produced during intraoperative moulding, easy re-
manufacturing on the pre-existing model in case of further complica-
tions and shorter operative time which, in turn, reduces intraoperative
blood loss [24].
A.A. Salam et al.
4.3. Bioactive fibre-reinforced composite cranioplasty
Fibre-reinforced composite with a bioactive glass particulate filling
is a new synthetic material for bone reconstruction which could over-
come the issue of bone resorption with autologous bone flap [15]. It is a
non-metallic, bioactive alternative for reconstruction of large skull de-
fects in the paediatric population [15].
The advantages of bioactive glass are it can chemically bond with
the bone and is osteoinductive, osteoconductive and also bacteriostatic
[15]. The glass-fibre-reinforced composite structure provides a high
strength and tough composite which allows the implant margins to be
thin [15]. The non-metallic composite implant is also non-magnetic,
relatively radiolucent and has low thermal conductivity [15].
Piitulainen et al. [15] used a glass-fibre-reinforced composite im-
plant in seven patients, aged 2.5–16 years, followed for 35 months.
They found that early outcomes with this implant were promising but
with high infection rate of 29 percentage. However, a long-term follow
up and a larger sample size will help giving statistically significant
conclusions on the disadvantages and complications from using the
aforementioned material, which are still unclear [15].
5. Published data
The following table summarises the various paediatric cranioplasty
materials used and reported complications requiring second cranio-
plasty from 2005 to 2016.
6. Future technologies
The production of natural materials via tissue engineering could
transform current treatment and would specifically be useful in pae-
diatric patients where there is increased donor site morbidity and less
autograft availability [32].
6.1. Bone morphogenic protein
Osteoinduction is the process by which undifferentiated mesench-
ymal cells in the bone are converted into osteoprogenitor cells with the
help of bone morphogenetic proteins (BMP) [32].Research in cranio-
plasty is shifting towards molecular biology to promote bone graft
healing with the help of introducing BMP into the implant to encourage
bone regeneration [11]. The use of BMP in the paediatric population
needs further investigation [32].
6.2. Growth factors
Various studies are being conducted using recombinant growth
factors such as transforming growth factor β, insulin-like growth
factor–I, and BMP-2 in augmenting calvarial closure in animal and
human models [32].
6.3. Stem cell therapy
Autologous adipose-derived stem cells (ADSCs) are seen as building
blocks for clinical cell therapy due to their abundance in availability,
unlike bone marrow stem cells, and can be easily harvested. ADSCs can
be easily expanded in vitro and undergo adipogenic, osteogenic,
chondrogenic, neurogenic, and myogenic differentiation [33].
Thesleff et al. [33] used a combination of beta-tricalcium phosphate
and ADSCs for cranioplasty in four adult patients and achieved well
ossified constructs post operatively without any complications. The
cytokines and chemokines produced by the transplanted ADSCs aid as
homing signals to endogenous stem cells and the osteoconductivity of
the beta-tricalcium phosphate together help in achieving ossification of
the construct [33]. This is a novel method and currently there are no
reports or studies published showing its use in paediatric patients.
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7. Discussion and conclusion
A better understanding of optimal material to use in the paediatric
population is necessary since children are at risk of undergoing multiple
surgeries for cranial reconstruction, having slow neurological recovery
or suffering from sunken flap syndrome [34].
The ideal material for cranioplasty has not been established thus far
in the literature. As demonstrated, even the so called gold standard of
autologous cranioplasty is fraught with issues of resorption. The com-
plexity of the growing skull in the paediatric population further com-
plicates the situation. Autologous bone graft continues to be the pre-
ferred choice for paediatric cranioplasty as it reduces the introduction
of foreign materials into the body and integrates into the skull quickly.
Traditionally for infants, particulate bone graft or exchange cra-
nioplasty has been preferred to split calvarial graft due to the thinness
of the skull. Contrary to this we found literature supportive of using
split calvarial graft for children younger than three years, and even as
young as two months of age.
For children less than seven years of age synthetic materials are
recommended due to the higher incidence of bone resorption. Also
customized bioceramic implant constituted of macroporous hydro-
xyapatite may be considered as another valid option for children under
7 years old, as the failure rate is comparatively lower than other ma-
terials currently in use.
It has been found that the use of customized PMMA avoids the
exothermic reaction of mouldable PMMA and is a better option for
children < 12 years age. For children aged between seven to 14 years
custom made porous hydroxyapatite or titanium mesh implants are
found to be safe.
There is no strong evidence currently suggesting any optimum
material for paediatric cranioplasty, due to lack of data and contra-
dictory evidence. All the existing studies have very small sample sizes.
Large scale, prospective studies are required to shed more light on this
topic. We are currently conducting a survey looking at the various
materials preferred by paediatric neurosurgeons in Australia.
Disclosure-conflict of interest
No disclosures or conflict of interest to report.
Acknowledgements
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
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