Original article 187

Triphasic ceramic scaffold in paediatric and adolescent

bone defects
Balasubramanian Balakumara, Suresh Babub, Harikrishna K. Varmab
and Vrisha Madhuria
We evaluated novel triphasic hydroxyapatite tricalcium
phosphate calcium silicate scaffold (HASi) in the
management of paediatric bone defects. Their main
advantage is considered to be adequate strength
and stimulation of bone formation without resorting
to autograft. A total of 42 children younger than 16 years
of age were recruited over a period of 1 year and were
treated with this synthetic bone substitute as a stand-alone
graft for pelvic, femur, calcaneal and ulnar osteotomies,
cystic bone lesions, subtalar arthrodesis and segmental
bone defects. Forty children, 22 boys and 18 girls, mean
age 8.3 years and a mean follow-up of 18.51 months, were
available for evaluation. Analysis showed that younger age,
cancellous defects and no internal fixation were associated
with significantly faster healing. Partial incorporation was
observed in 22.5% and complete incorporation in 77.5%
of cases at 18 months of follow-up. Sex, type of defect, BMI
and the shape of the ceramic graft did not significantly

Introduction
Surgical management of many orthopaedic conditions
requires fillers to bridge the bone defects. Autologous
bone grafts provide the ideal replacement for such
defects with its inherent property of osteogenesis,
osteoinduction and osteoconduction [1]. As there are
many associated complications such as donor site
morbidity, limited availability and an additional surgical
procedure for the harvest in the autologous bone grafts,
there is a need for bone graft substitutes [1]. The
prerequisites for an ideal bone graft substitute are
nonimmunogenicity, sterility, mechanical strength, bioresorbability, easy availability and low cost. It is desirable
for it to have osteogenic, osteoinductive and osteoconductive properties [2,3]. A bone substitute acts as a
scaffold for bridging the bone defect and later allows
gradual replacement by regenerating bone.
Bone graft substitutes have been classified depending on
their source into allograft, cell, growth factor, ceramic,
polymer based and miscellaneous [4]. Ceramic-based
bone graft substitutes include hydroxyapatite, calcium
phosphate, tricalcium phosphate or bioglass. Hydroxyapatite-based scaffolds are the most preferred substitutes
for bone reconstruction as natural bone has similar
stoichiometry [5]. Preclinical studies have shown that
bioglass (silica) is helpful in bone formation [6]. Silicatecontaining calcium phosphate ceramics have been shown
c 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
1060-152X

affect the rate of healing. Complications attributable

to HASi included four nonunions, three of which were
diaphyseal. HASi was found to be safe in children with
cancellous or benign cavitatory defects. It is not suitable
for diaphyseal and segmental bone defects as a
stand-alone graft. J Pediatr Orthop B 23:187195

c 2014 Wolters Kluwer Health | Lippincott Williams &
Wilkins.
Journal of Pediatric Orthopaedics B 2014, 23:187195
Keywords: bone substitutes, child, HASi, incorporation, synthetic grafts
a
Paediatric Orthopaedic Unit, Christian Medical College, Vellore, Tamil Nadu
and bBioceramic Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal
Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India

Correspondence to Vrisha Madhuri, MBBS, MS, MCh, Paediatric Orthopaedic

Unit, Christian Medical College, Paul Brand Building, Ida Scudder Road,
Vellore 632004, Tamil Nadu, India
Tel: + 91 416 228 2172; fax: + 91 416 223 2305;
e-mail: madhuriwalter@cmcvellore.ac.in

to enhance bone formation and spinal fusion [7,8].

Bioglass alone is used clinically in dental surgeries [9].
A novel triphasic calcium phosphorous silicate scaffold
(HASi) has been developed, which has the ideal ratio of
calcium phosphate and silica ceramic composition for
mesenchymal stem cell growth shown in both in-vivo and
in-vitro studies [10,11], and is now commercially available. This is a feasibility study of the use of this triphasic
scaffold for bone defects in children. The scaffold is a
composite of hydroxyapatite, b tricalcium phosphate and
calcium silicate. It has been used previously in adults for
filling the defects in the iliac crest donor sites [12], as a
plug for burr holes in the skull [13] and in posterolateral
instrumented lumbar fusion [14]. Although there are
many studies on adults, there are no reports on their
efficacy and safety in children.

Patients and methods

This study was carried out in children younger than 16
years of age who required bone graft for cavitatory,
cancellous or cortical defects. Institutional review board
approval and parental consent were obtained. The HASi
was used for pelvic osteotomies, shelf procedures, calcaneal
lengthening osteotomies, ulna osteotomy for neglected
Monteggia, subtalar arthrodesis, valgus osteotomy of the
proximal femur, primary grafting for comminuted intercondylar fracture of the humerus, segmental bone defects
DOI: 10.1097/BPB.0000000000000004

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188

Journal of Pediatric Orthopaedics B 2014, Vol 23 No 2

and benign bone tumours. No additional bone graft, cells or

any other bone substitute was used in these cases. A total
of 42 children were enrolled in this study over a period of
1 year.
Materials

HASi is a composite of hydroxyapatite and a bioactive glass

ceramic in the ratio of 80 : 20 [15]. The heat sintering
process is used in its manufacture, and a low-temperature
solgel method yields this bioglass ceramic without melting
or annealing. HASi has 70% porosity, with pore size ranging
from 50 to 500 mm (Fig. 1). Crystallinity, phase purity, trace
element/chemical analysis and toxicological screening have
been carried out for the composite. Animal experimentation and human clinical trials with this scaffold have been
reported [1016].

the routine postoperative rehabilitation similar to those who

received autograft for a similar condition in our institution.
The primary outcome measure was status of incorporation of
the graft at follow-up radiologically. The secondary outcome
measure was clinical outcome, that is, time to return to
preoperative activity status and complications if any.
Ten children, age, sex and disease matched, who received
a concurrent autologous bone graft for pelvic osteotomy
were included in a control group. To assess the rate of
HASi graft incorporation and time to return to weight
bearing in relation to autologous bone graft (standard of
care), pelvic osteotomy patients with HASi were
compared with the age-matched, sex-matched and
disease-matched controls treated with autografts.
Assessment of graft incorporation

Technique

To maintain uniformity, the standard surgical technique

was followed for all procedures and the resultant bone
defect or voids were filled with HASi bone graft substitute.
The grafts were shaped as blocks, wedges and pellets
(Fig. 2). Steam sterilization was carried out in an
autoclave at 1211C for 20 min.
The pellets were used to fill cavity defects. The blocks
were used for longitudinal defects. Both blocks and
wedges were used for osteotomies. Trimming of the
ceramic block to the required size was performed using a
power saw or a bone cutter depending on the surgical
need. The blocks were impacted into place. The standard
operating and postoperative protocol was used on the
basis of the indication for surgery.
All children were asked to return for follow-up at 3, 6, 12, 18
and 24 months after surgery. The complications were
recorded and treated appropriately. The children underwent

Ceramic incorporation was classified as complete if there

was trabecular continuity throughout the graft, with loss
of radio-opacity and gradual blurring of the sharp margins
of the HASi block. If such changes were noted only on
the surface of the block, it was classified as partial
incorporation [12]. The classifications were carried out by
two independent observers.
The height of the graft used was evaluated serially for
collapse and disintegration. The height was measured
using the distance measurement tool in the Picture
Archival and Communication System (PACS) and manual
measurement was performed on a paper tracing with
a centimetre scale to verify the PACS values.
Grouping of patients for analysis of results

To analyse the effectiveness of this scaffold in different

regions of bone, the patients were grouped as those with
cancellous (pelvic, metaphyseal, calcaneus) and cortical
(diaphyseal) defects. To analyse the effect of contact

Fig. 1

(a, b) Scanning electron micrographs of triphasic calcium phosphorous silicate scaffold (HASi) showing a highly interconnected porous structure
with 50500 mm pore diameter. Magnification: (a) 10 000  , (b) 100  .

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Ceramics in paediatric bone defects Balakumar et al.

189

Fig. 2

Triphasic calcium phosphorous silicate scaffold (HASi) can be shaped as cylindrical blocks, wedges and pellets.

surface area available for healing, the defects were

classified as contained (cysts) and uncontained defects
(open wedge and gap defects). Confounders such as
internal fixation and BMI were included in the analysis.
The data were analysed using STATA 10.0 software
(STATA Corp., College Station, Texas, USA). The Mann
Whitney U-test was used for a nonparametric statistical
hypothesis between two independent samples, Fischers
exact test was used for categorical data, the Wilcoxon
signed-rank test was used for a nonparametric statistical
hypothesis for comparison of two related data. A P value
of less than 0.05 was considered statistically significant.

Results
A total of 40 children were available for follow-up for a
mean duration of 18.51 months. Two children were lost to
follow-up. One was contacted over the phone and refused
to come for review as the child was asymptomatic. The
other did not respond to the letter. These two were
excluded from the analysis.
The average age of the 40 children available for further
evaluation was 8.3 years (SD, 4.287; range, 116 years).
There were 22 boys and 18 girls. The indications for use of
the HASi ceramic scaffold were pelvic osteotomies and
shelf procedures in 13 patients, calcaneal lengthening
osteotomies in five, ulna angulation osteotomies in four,
subtalar arthrodesis in two, valgus osteotomy of the femur
in two, primary grafting for comminuted fracture humerus

in one, segmental bone defects in three and benign bone

tumours in 10. There were 33 patients with cancellous and
seven with cortical defects. The defects were classified as
contained in eight and uncontained in 32 patients.

Clinical results

A total of 35 children (87.5%) recovered from surgery

following the use of a scaffold as a bone graft substitute
without complications. The average time to return to
preoperative activity level was 2.77 months (range,
1.53.5 months; SD, 0.43) and clinical evaluation at
follow-up showed no pain, discharge or wound complications at the HASi graft site in these 35 children.
Radiologically, these 35 children showed either partial or
complete incorporation of the graft. There were complications in the remaining five children. Four children had
nonunion; three of whom were diaphyseal and three
underwent autologous cancellous bone grafting as treatment. In the fifth child, there was an infection at the
operated site after 1 month, secondary to multiple skin
pustules over the face and lower limbs, and bacteraemia,
which resulted in infection requiring removal of the
scaffold and implant with eventual malunion.

Radiological results

The radiographs of the 35 healed children evaluated

serially at follow-up visits yielded the following results:

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190

Journal of Pediatric Orthopaedics B 2014, Vol 23 No 2

Distribution of stage of incorporation according to the

complete/partial system among the various subgroups analysed
at 12 months of follow-up

Percentage of cases with

partial incorporation

Fig. 3

Table 1

100
90
80
70
60
50
40
30
20
10

Subgroups

45.8
25.8

22.5

12
18
Duration of follow-up (months)

17.2
24

Bar diagram showing time versus incorporation of graft. It could be

noted that with a longer duration of follow-up, the percentage of partial
incorporation decreases proportionately. Of the cases, 77.5% have
complete incorporation of graft at 1 years of follow-up.

Six cases were in the partially healed stage and 29 were in

the completely healed stage at the last follow-up.
Complete healing occurred in 19 cases at 6 months and
26 cases at 12 months. Partial healing was noted in 16
cases at 6 months and in nine cases at 12 months (Fig. 3).
Cohens weighted k for inter-rater agreement of radiographic scoring for these cases was 0.8207 (95%
confidence interval 0.55181.0896), indicating fair agreement between the observers.
Subgroup analysis is shown in Table 1.
The MannWhitney U-test showed significantly rapid
healing in younger children younger than 10 years of age
(P = 0.0213), those with cancellous defects (P = 0.0169)
(Fig. 4) and with a longer duration of follow-up
(P < 0.0075). The division of children into less than 10
years and 10 years or more of age as a determinant for
bone healing was based on the median age of 9 years.
There was no statistically significant difference in the
rate of healing between contained and uncontained bone
defects (P = 0.7) (Fig. 5) and between wedges and
granules (P = 0.094).
Fischers exact test showed a significantly faster healing
rate in children who had no internal fixation
(P = 0.0003); there was no difference in the rate of
healing on the basis of BMI (P = 0.7043) and no
difference in the height of the graft on serial follow-up
indicating structural integrity of graft (P = 0.10) in the
uncomplicated cases. The interclass correlation coefficient for the height measurement was 0.7704, indicating
strong agreement between the observers.
The MannWhitney U-test for acetabular index correction following pelvic osteotomy between cases and
control showed no loss of correction (P > |z| = 0.1026).
The w2-test showed a significant difference in the stage
of healing between the cases and the controls

Complete incorporation (n)

Age (years) (n = 35)

< 10
> 10
Sex (n = 35)
Male
Female
Follow-up time (months) (n = 35)
<6
>6
Type of defect (n = 35)
Contained
Uncontained
Location of the defect (n = 35)
Cortical
Cancellous
Shape of the substitute (n = 35)
Wedges
Granules
BMI (n = 31)
> 20
< 20
Internal fixation (n = 35)
Yes
No

Partial incorporation (n)

19
7

5
4

15
11

4
5

1
25

4
5

1
25

7
2

2
24

5
4

12
14

5
4

12
10

4
5

1
25

6
3

Failed cases were excluded from the analysis. BMI data were available only for
31 cases.

(P = 0.001), indicating that an autologous bone graft

has a faster incorporation rate. The average time to
complete incorporation for autologous graft was 3 months,
whereas it was 6 months for the study cases. The average
time to return to preoperative activity status was 2.5
months for the control group and 2.7 months for the
study group, which was statistically not significant.
Complications

The time to return to preoperative activity level for

complicated cases was delayed by an average of 10
months.
Infection and malunion

One child had infection with a failed implant following

valgus osteotomy for congenital coxa vara, which was
managed with implant exit and antibiotic-loaded ceramic
bead implantation. This complication was unrelated
to the presence of HASi. Per operative evaluation during
implant exit showed that the graft was incorporated
at the osteotomy site with no abnormal mobility
(Fig. 6). Biopsy from the grafted site showed fibrovascular
tissue infiltration in the graft with partial resorption
(Fig. 7).
Nonunion

Nonunion was observed in four cases. Three children

with external fixator (Orthofix, Verona, Italy) application
and HASi cylindrical blocks for diaphyseal segmental
defects failed to show progressive union at 5 months and
had fixator loosening with pin-site infection. The HASi

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Ceramics in paediatric bone defects Balakumar et al. 191

Fig. 4

Serial radiographs of a 4-year-old child with residual acetabular dysplasia treated with Dega osteotomy using a triphasic calcium phosphorous
silicate scaffold (HASi) graft. (a) Preoperative image showing acetabular dysplasia 4 years after open reduction. (b) Fluoroscopy image showing
Dega osteotomy with an HASi graft for the open wedge. (c) Two months follow-up. (d) Nine months follow-up with incorporation of HASi. There is
persistent dysplasia, in addition to coxa valga at follow-up.

Fig. 5

Serial radiographs showing proximal humerus chondroblastoma in an 11-year-old boy presenting as a contained defect treated with curettage and a
triphasic calcium phosphorous silicate scaffold (HASi) graft. (a, b) Preoperative images of the right proximal humerus showing a lytic lesion in the
proximal humerus epiphyseal region. (c) Radiographs after intralesional curettage and HASi filling. (d, e) One year after curettage. (f) Twenty-one
months follow-up with partial incorporation.

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192 Journal of Pediatric Orthopaedics B 2014, Vol 23 No 2

Fig. 6

Serial radiographs of a 10-year-old boy with developmental coxa vara left proximal femur. (a) Preoperative radiographs showing recurrent coxa
vara after a valgus osteotomy and blade plate fixation. (b) Redo valgus osteotomy and fixation with an angled blade plate and a triphasic calcium
phosphorous silicate scaffold (HASi) for the defect. (c) Four months after osteotomy with infection and partial incorporation. (d) Complete healing
of the osteotomy with resolution of infection and recurrent coxa vara typical of the natural history of developmental coxa vara at the 2-year follow-up
after implant exit and debridement.

Fig. 7

(a)

250 m

(b)

50 m

Photomicrographs of the triphasic calcium phosphorous silicate scaffold (HASi) substitute retrieved during implant exit and debridement in the child
who had infection. (a) Fibrous tissue ingrowth was observed in most of the pores (haematoxylin and eosin stain, 4 ) (small arrows). (b) Fibrous
tissue ingrowth with angiogenesis (arrows) in the pores of the scaffold (Stevenels Blue stain, 20 ).

block and fixator were removed and treated with

autologous iliac crest bone grafting in one child, ipsilateral
vascularized fibula grafting in another child (Fig. 8) and
Ilizarov ring fixation in the third child. Biopsy of the
removed HASi indicated fibrovascular stroma in the pores.
An adolescent with onycho-osteodysplasia with acetabular
dysplasia underwent periacetabular osteotomy with the
HASi graft implanted into the large iliac defect. At the 1year follow-up, there was graft displacement and painful
nonunion. The graft was removed and the defect was
treated with autologous cancellous bone grafting from the
iliac crest and a shelf was added to improve the femoral
head coverage. The symptoms resolved and the osteotomy
healed within 3 months.

Discussion
The scaffold used in this study is biocompatible by virtue
of hydroxyapatite and bioresorbable by virtue of bioglass.
With many descriptive studies of its use in adults
published in the literature, we have explored its
usefulness in children who have a limited autograft
supply. This is the first study to use HASi to establish its
safety profile in children. The findings in this feasibility
study showed that HASi is safe in this short-term study
without any serious adverse events or local wound
complications for cancellous, metaphyseal and contained
bone defects, although complete incorporation takes
longer than autograft. Infection in one case was because
of impetiginous skin infection and probably not related to

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Ceramics in paediatric bone defects Balakumar et al. 193

Fig. 8

Serial radiographs of a 5-year-old child with postseptic gap nonunion managed with distraction and external fixation (Orthofix, Verona, Italy).
(a, b) Preoperative radiographs anteroposterior and lateral view showing segmental bone loss in the tibia. (c) Treatment with triphasic calcium
phosphorous silicate scaffold (HASi) cylinder implantation in the bone defect and stabilization with an external fixator. (d, e) At 3 months after the
procedure, some incorporation was noted at the distal end. (f, g) Five months after surgery, with no evidence of incorporation at the proximal end of
the cylinder bridging the bone defect. (hj) Eventually, the defect was treated with an ipsilateral vascularized fibular graft, which united at 2.5 months
of follow-up.

the graft. There were no local wound complications in

those children who had the graft for more than 1 year
in vivo. The scaffold has been shown to maintain the
height in the open wedge osteotomies without collapse
and showed healing in cavitatory defects. There was no
delay in rehabilitation. Younger children and cancellous
defects had a better healing response and faster
incorporation in our study. This probably reflects the
greater remodelling capacity in the younger children.
Diaphyseal and segmental bone defects had poor healing
with the HASi ceramic as a stand-alone graft.
Hydroxyapatite as a bone graft substitute has been used in
the treatment of defects following benign bone tumours.
Matsumine et al. [17] found that resorption was faster in
younger children and males at a mean of 11.4 years
of follow-up. Yamamoto et al. [18] used a composite of

hydroxyapatite and tricalcium phosphate (70 and 30%) in

benign bone tumours with excellent results at 41.3 months
of follow-up. However, the graft was not completely
resorbed in any case in both series. The biodegradability
of hydroxyapatite is influenced not only by the normal bone
turnover kinematics but also by the pore diameter, shape,
manufacturing process and pore connectivity. A composite
of hydroxyapatite and calcium sulfate had been used by
Schindler et al. [19] for the treatment of benign bone
tumours with osteointegration, and consolidation was
achieved by 24 months. The biological response in children
differs from adults. In this study, we explored various
clinical situations to determine the best possible application for HASi. It was found that the use of the HASi
scaffold was safe in children with cancellous bone defects,
with no minor or major adverse events attributable to HASi
noted in the postoperative period.

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194

Journal of Pediatric Orthopaedics B 2014, Vol 23 No 2

Evaluation of our results shows that there is rapid

bonding of the graft with the native bone in 54.2% of
cases by 6 months. By 1 year, 74.2% of cases showed
complete replacement of the graft by bone. The
metaphyseal sites and younger children had a rapid
healing response compared with the diaphyseal region
and older children. Biologically, this could be explained by
the lack of osteogenic potential in the scaffold. The
abundant cancellous raw bone apposition in the metaphyseal defects has a greater osteogenic potential than
the diaphyseal regions. Delecrin et al. [20] had shown
that the environment of the ceramic determines the
kinetics of its incorporation. Their animal model showed
that close contact with the freshened raw host bone
determines the bony ingrowth. This explains the early
incorporation at the metaphyseal regions in our study.
The rapid healing in the uncontained defects observed in
our series can be postulated to be because of the larger
area available. In a younger child, thick periosteum
supports rapid healing response [21].
The graft incorporation was proportional to the duration of
follow-up. Because of the property of mechanical stability,
bioresorbability and bioactivity, this composite scaffold had
a faster radiological incorporation in cancellous defects than
shown by other hydroxyapatite ceramics in the medical
literature. The incorporation time is 6 months for HASi in
cancellous defects and 18 months in cortical defects. Time
to incorporation of hydroxyapatite-based ceramics reported
in the literature varied from 9 months to more than a
year [22,23]. This is because of the rapid bonding property
of the bioglass component in the ceramic [14]. The
hydroxyapatite base maintains the framework for bony
ingrowth, whereas the faster degradable bioglass component releases silicate and orthophosphate ions into the
physiological milieu and leads to earlier incorporation [14].
The radiodense appearance of the graft for a longer time is
because of the hydroxyapatite component, which takes a
protracted duration to disappear, but the strength of
incorporation is not compromised [17]. Even when the
incorporation of HASi was partial in radiographs, it did not
interfere with rehabilitation and weight bearing similar to
previous studies, which used a hydroxyapatite bone
substitute [22,23].
Complications have been noted in studies that used HASi
in adults. Graft migration, persistent pain [12], delayed
incorporation [13] and failure of spinal fusion have been
reported [14]. Localized inflammation, delayed incorporation and foreign body granuloma have been reported
with calcium phosphate and hydroxyapatite, respectively [5,24]. No localized inflammation caused by HASi
was observed in children in this study.
All three children with segmental cortical bone defect had
failure of graft incorporation in our series and required
secondary procedures. Hence, the scaffold as a stand-alone
graft was considered inadequate to heal segmental defects

as it does not have osteogenic potential. These sites may

have inadequate periosteum because of previous surgeries
and limited mesenchymal stem cells in the milieu to
migrate to the scaffold. This concern opens up a new
research question of how to improve the incorporation of
the scaffold under these conditions. Many studies have
been carried out testing other scaffolds for segmental
critical-sized bone defects in animals and to date three
human studies have been reported. All the studies have
found scaffolds alone to be insufficient and addition of
stem cells and growth factors is advocated [2528]. On the
basis of this, tissue-engineered HASi with seeding of
mesenchymal stem cells has been attempted in criticalsized segmental diaphyseal bone defects in goats by Nair
et al. [29]. Their study showed that tissue-engineered HASi
incorporated faster with good bone formation than the
scaffolds alone in the defects.
There are some limitations in this study. The sample size
was small and the follow-up duration was short.
Histopathological examination was available only for
failed cases as the other children did not need a repeat
open surgery. Confounders such as use of a power saw for
osteotomies and time to weight bearing by the patient
were not included in this analysis. Disease groups with
different pathologies have been included in this study.
Also, we have not assessed graft incorporation with a
computerized scan or a DEXA scan because of the
presence of metallic implants.
Conclusion

We conclude that HASi plays a definite role in paediatric

metaphyseal and cancellous bone defects and spares the
native donor bone. In the diaphyseal bone defects, it is
not recommended as a stand-alone graft. The role of
HASi as a graft for segmental defects in children with
bone marrow or mesenchymal stem cells in such
situations remains to be explored.

Acknowledgements
The authors thank Dr Deepthi Katulla, BDS, MSc
(Epidemiology), PhD, Senior Research Fellow, for the
statistical analysis.
Conflicts of interest

There are no conflicts of interest.

References
1

Dimitriou R, Mataliotakis GI, Angoules AG, Kanakaris NK, Giannoudis PV.

Complications following autologous bone graft harvesting from the iliac crest
and using the RIA: a systematic review. Injury 2011; 42:S3S15.
Janicki P, Schmidmaier G. What should be the characteristics of the ideal
bone graft substitute? Combining scaffolds with growth factors and/or
stem cells. Injury 2011; 42:S77S81.
Hannink G, Arts JJ. Bioresorbability, porosity and mechanical strength of
bone substitutes: what is optimal for bone regeneration? Injury 2011;
42:S22S25.
Laurencin C, Khan Y, El-Amin SF. Bone graft substitutes. Expert Rev Med
Devices 2006; 3:4957.

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Ceramics in paediatric bone defects Balakumar et al. 195

5
6

7
8

10

11

12

13

14

15

16

17

Giannoudis PV, Dinopoulos H, Tsiridis E. Bone substitutes: an update. Injury

2005; 36:S20S27.
Valerio P, Pereira MM, Goes AM, Leite MF. The effect of ionic products from
bioactive glass dissolution on osteoblast proliferation and collagen
production. Biomaterials 2004; 25:29412948.
Waked W, Grauer J. Silicates and bone fusion. Orthopedics 2008;
31:591597.
Jenis LG, Banco RJ. Efficacy of silicate-substituted calcium phosphate
ceramic in posterolateral instrumented lumbar fusion. Spine 2010;
35:10581063.
Froum SJ, Weinberg MA, Tarnow D. Comparison of bioactive glass synthetic
bone graft particles and open debridement in the treatment of human
periodontal defects a clinical study. J Periodontol 1998; 69:698709.
Nair MB, Varma HK, Kumary TV, Babu S, John A. Cell interaction studies
with novel bioglass coated hydroxyapatite porous blocks. Trends Biomater
Artif Organs 2006; 19:108114.
Nair MB, Suresh Babu S, Varma HK, John A. A triphasic ceramic-coated
porous hydroxyapatite for tissue engineering application. Acta Biomater
2008; 4:173181.
Acharya NK, Mahajan CV, Kumar RJ, Varma HK, Menon KV. Can iliac crest
reconstruction reduce donor site morbidity?: a study using degradable
hydroxyapatite-bioactive glass ceramic composite. J Spinal Disord Tech
2010; 23:266271.
Easwer HV, Rajeev A, Varma HK, Vijayan S, Bhattacharya RN. Cosmetic and
radiological outcome following the use of synthetic hydroxyapatite porousdense bilayer burr-hole buttons. Acta Neurochir (Wien) 2007;
149:481485.
Acharya NK, Kumar RK, Varma HK, Menon VK. Hydroxyapatite-bioactive
glass ceramic composite as standalone graft substitute for posterolateral
fusion of lumbar spine: a prospective, matched and controlled Study.
J Spinal Disord Tech 2008; 21:106111.
Nair MB, Varma HK, John A. Triphasic ceramic coated hydroxyapatite as
a niche for goat stem cell-derived osteoblasts for bone regeneration and
repair. J Mater Sci Mater Med 2009; 20:S251S258.
Nair MB, Varma HK, Menon KV, Shenoy SJ, John A. Reconstruction of goat
femur segmental defects using triphasic ceramic-coated hydroxyapatite in
combination with autologous cells and platelet-rich plasma. Acta Biomater
2009; 5:17421755.
Matsumine A, Myoui A, Kusuzaki K, Araki N, Seto M, Yoshikawa H, Uchida A.
Calcium hydroxyapatite ceramic implants in bone tumour surgery. A longterm follow-up study. J Bone Joint Surg 2004; 86:719725.

18

19

20

21
22

23

24

25

26

27

28

29

Yamamoto T, Onga T, Marui T, Mizuno K. Use of hydroxyapatite to fill cavities

after excision of benign bone tumours clinical results. J Bone Joint Surg
2000; 82:11171120.
Schindler OS, Cannon SR, Briggs TW, Blunn GW. Composite ceramic
bone graft substitute in the treatment of locally aggressive benign bone
tumours. J Orthop Surg (Hong Kong) 2008; 16:6674.
Delecrin J, Aguado E, NGuyen JM, Pyre D, Royer J, Passuti N. Influence of
local environment on incorporation of ceramic for lumbar fusion: comparison
of laminar and intertransverse sites in a canine model. Spine 1997;
22:16831689.
Lindaman LM. Bone healing in children. Clin Podiatr Med Surg 2001;
18:97108.
Saikia KC, Bhattacharya TD, Bhuyan SK, Talukdar DJ, Saikia SP, Jitesh P.
Calcium phosphate ceramics as bone graft substitutes in filling bone tumor
defects. Indian J Orthop 2008; 42:169172.
Bansal S, Chauhan V, Sharma S, Maheshwari R, Juyal A, Raghuvanshi S.
Evaluation of hydroxyapatite and beta-tricalcium phosphate mixed with bone
marrow aspirate as a bone graft substitute for posterolateral spinal fusion.
Indian J Orthop 2009; 43:234239.
Ogose A, Hotta T, Kawashima H, Kondo N, Gu W, Kamura T, Endo N.
Comparison of hydroxyapatite and beta tricalcium phosphate as bone
substitutes after excision of bone tumors. J Biomed Mater Res B Appl
Biomater 2005; 72:94101.
Yuan J, Zhang WJ, Liu G, Wei M, Qi ZL, Liu W, et al. Repair of canine
mandibular bone defects with bone marrow stromal cells and coral. Tissue
Eng Part A 2010; 16:13851394.
Pneumaticos SG, Triantafyllopoulos GK, Basdra EK, Papavassiliou AG.
Segmental bone defects: from cellular and molecular pathways to the
development of novel biological treatments. J Cell Mol Med 2010;
14:25612569.
Marcacci M, Kon E, Moukhachev V, Lavroukov A, Kutepov S, Quarto R, et al.
Stem cells associated with macroporous bioceramics for long bone
repair: 6- to 7- year outcome of a pilot clinical study. Tissue Eng 2007;
13:947955.
Quarto R, Mastrogiacomo M, Cancedda R, Kutepov SM, Mukhachev V,
Lavroukov A, et al. Repair of large bone defects with the use of
autologous bone marrow stromal cells. N Engl J Med 2001;
344:385386.
Nair MB, Varma H, Shenoy SJ, John A. Treatment of goat femur segmental
defects with silica-coated hydroxyapatite one-year follow-up. Tissue Eng
Part A 2010; 16:385391.

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