Individualized techniques of Implant Coating with
an Antibiotic-loaded, Hydroxyapatite/Calcium sulphate Bone Graft Substitute
Holger Freischmidt1, Jonas Armbruster1, Gregor Reiter1, Paul Alfred Grützner1, Lars Helbig2 and Thorsten Guehring3*
1BG Unfallklinik Ludwigshafen, Klinik für Unfallchirurgie und Orthopädie, Ludwig-Guttmann-Strasse 13, 67071 Ludwigshafen, Germany
2Clinic for Orthopedics and Trauma Surgery, Center for Orthopedics, Trauma Surgery and Spinal Cord Injury, Heidelberg University Hospital, Germany
3Arcus Kliniken Pforzheim, Germany
Submission: November 19, 2019;Published: December 02, 2019
*Corresponding author: Pilar Aparicio, Upper Limb and Microsurgery Unit, Orthopaedics Department, Parc Sanitari Sant Joan de Déu de Sant Boi de Llobregat, Barcelona, Spain
How to cite this article: Holger F, Jonas A, Gregor R, Thorsten Guehring, et al. Individualized techniques of Implant Coating with an Antibiotic-loaded,
Hydroxyapatite/Calcium sulphate Bone Graft Substitute. Ortho & Rheum Open Access J. 2019; 15(3): 555912. DOI: 10.19080/OROAJ.2019.14.555912
Background: The treatment of fracture- or non-union- related infections has persistently been a major challenge for both patients and treating surgeons. With rising aging of patients and increasing comorbidities, combined with the heterogeneity of germs and any number of multi-resistance against standard antibiotics, a successful treatment is increasingly difficult. One potential solution could be a custom-made individualized antibacterial coating of standard implants with a biphasic degradable biocarrier that releases high doses of antibiotics around the bone-implant-interface. Here we describe our technique of coating intramedullary nails, plates and press-fit shoulder endoprostheses which may prevent bacterial adhesion and biofilm formation. So far, there is very limited experience in individual coating of implants in hip or knee endoprostheses to prevent reoccurrence of surgical-site infection. Currently no reports are available for coating of stems of shoulder prosthesis and nails or plates for fracture fixation.
Methods: Here we show our first experiences with a new individualized surgical technique of coating these implants with a resorbable antibiotic-loaded hydroxyapatite / calcium sulphate biocomposite to prevent biofilm formation and thereby recurrence of bone or joint infection. We describe three cases for coating of plates and nails for fracture fixation and coating of stems of a shoulder prosthesis.
Results: No adverse events of the resorbable bone graft substitute were observed. In all the cases no recurrence of the infection was observed, and osseo-integration was achieved. After implant coating of the shoulder prosthesis no radiological signs of loosening were detected
Conclusion: We present a new surgical approach of a surface coating of plates, intramedullary nails or prostheses. The osteoconductive- and anti-inflammatory effect of the gentamicin- or vancomycin-loaded hydroxyapatite / calcium sulphate bone graft substitutes shows promising results.
Keywords: Fracture related infections; Osteitis; Osteosynthesis; Local antibiotics; Biodegradable biocomposites
Fracture-related infection (FRI) or periprosthetic infection (PJI) remain a major challenge in orthopedic and trauma surgery. Particularly patients with relevant comorbidities such as diabetes, renal failure, peripheral vasculopathy and known nicotine abuse have a high risk for implant- related infections . Numerous devices for local antibiotic application and several treatment options are already available. The aim of these devices is to release local antibiotics in high concentration over a prolonged time period , and a new generation of bio-degradable carriers for local antibiotic delivery have been recently emerging for utilization . One of the major difficulties arises from of the ability of microorganisms to adhere to the implant and produce a biofilm layer which unfortunately hinder the treatment of implant-related infections [4-6]. A promising solution could be a commercially available coating of implants such as tibia intramedullary nails. Currently, however the „Expert tibial nail PROtect“(Fa. DePuy Synthes) is the only factory-made antibiotic coated implant available on the market. However, the antibiotics delivery of this coated implant is limited to gentamicin, and it is rather expensive.
As one of the promising biodegradable biocomposites
Cerament (supplied by Bone support AB, Lund, Sweden) is
an injectable bone graft substitute, composed of 60% fast
resorbing calcium sulphate and 40% calcium hydroxyapatite
. The resorbable local antibiotic carrier provides two
modes of actions. It remodels to bone and it provides a local
antibiotic concentration which is above the minimal inhibitory
concentration (MIC) for most sensitive microorganisms for at
least 28 days with - at the same time - safe serum levels [8-10].
The local administration of the antibiotic-containing ceramics
promises a better anti-infectious effect than local injection
or intravenous infection. Clinical trials demonstrated that
Cerament is a viable replacement to bone grafting in filling voids
and gaps following fractures . However, in recent literature
there is clear evidence of lower infection rates in after additional
local antibiotics at least in grade III open fractures . Early
histology of Cerament G in Ferguson et al.  shows nicely the
CERAMENT G covered by an osteoid-like matrix produced by
osteoblastic cells seen lining the bone graft substitute’s surface.
Additionally, Cerament showed good tissue response in an
animal model including growth of trabecular bone around the
hydroxyapatite particles and complete embedment in bone
tissue . Furthermore, Cerament is commercially available
with two antibiotic-loaded options. It is marketed as Cerament
G (17.5 mg gentamicin sulphate / ml paste) and Cerament V (66
mg vancomycin / ml paste) as 5 ml and 10 ml version.
The efficacy of Cerament G and Cerament V in treatment of
infected bone defects has already been demonstrated in both
osteomyelitis and fracture related infections [3,14,15], as well
as in various animal models [16-19]. In an in vitro study the
anti-biofilm activity of Cerament G was investigated, suggesting
a benefit of this gentamicin-releasing biocomposite for both
prophylaxis and treatment of bone infection or implant-related
infection, respectively . However, clinical reports on the usage of Cerament G/V as off-label coating device are limited so far. The first clinical experience in using a calcium-based gentamicin or
vancomycin loaded bone graft substitute as a surface coating on
cement less prosthetic implants has been published by Logoluso
et al. In this study 95% of patients treated for PJI with a twostage
revision showed healing without recurrence of infection
and no signs of radiographic stem loosening appeared at 12
months follow up . In the here described method we aim to
cover each individual implant with Cerament G or Cerament V.
This method thus enables to individually coat the most suitable
implant (i.e. plates or nails in fracture treatment). In PJI the
revision stems of the protheses can be augmented with the most
suitable and effective antibiotics (i.e. gentamicin or vancomycin)
by augmenting the stem with Cerament G or V. After coating
the stem is inserted in a press-fit technique. In the following
presentation of our operative technique we provide three new
surgical techniques to coat different implants with an antibioticloaded,
hydroxyapatite / calcium sulphate bone graft substitutes
in order to address the heterogeneity of both microorganism
and surgical site.
A 38-year-old male patient fell of a ride-on mower which then
rolled over his left lower leg. This resulted in a second-degree
open fracture of the lower limb. Hence, wound debridement
and external fixation were performed. The microbiologic results
showed an infection with enterobacter intermedius and serratia
fonticola. Both microorganisms were sensitive to gentamicin.
One month after the accident and several debridements later,
the external fixator was removed, and the tibia was stabilized
with a low compression plate (LCP). In addition, the tibial defect
was filled, and the plate was augmented with 5 ml Cerament G to
prevent infection. Finally, the soft tissue defect was closed with
an ALT flap by the plastic surgeons (Figure 1).
A 35-year-old male patient fractured his left femur shaft
in a traffic accident in Egypt. Initially, the closed femoral shaft
fracture was treated on site with an intramedullary nail. One
year later bone healing could not be observed, and the patient
still suffered from pain due to a non-union. Therefore, we
performed a resection of the non-union and the left femur was
immobilized with an external transport fixator as there was a
significant shortening of the leg. An infected non-union was
diagnosed and a MRSA could be intraoperatively isolated from
the non-union site. A bone lengthening was approached for 2
months via the external fixator. However, the lengthening failed
due to insufficient stability, and even though a rigid external
fixator was subsequently applied for another 6 months, no
bone healing could be achieved. Metal removal and complete
en bloc resection of the non-union was done and a vancomycin
loaded cement spacer was inserted intramedullary. No MRSA
was detected during this procedure. As a next step, the cement
spacer was removed and a nail-osteosynthesis was inserted
after the medullary canal had been reamed (LFN 360/16 mm,
Fa Synthes). Before insertion, the nail was augmented with
Cerament V (Figure 2b). and the medullary canal was filled up
with the remaining amount of Cerament V using an extension
tube A total of 10 millilitres of Cerament V was utilized (Figure
2). Finally, two years after the accident, the nail was dynamically
locked for dynamic compression of the non-union. Full weight
bearing of the left lower extremity was possible immediately.
After 22 months a complete bone healing was achieved (Figure
A 57-year-old female patient presented with a loosening of
a proximal humeral nail (PHN, Fa. Synthes) after fractured left
humeral head due to a fall on her shoulder. As reason for the
loosening an infection with extensive abscess formation around
the implant was identified. The situation was complicated by the
patient‘s incompliance and comorbidities such as schizophrenia.
In the first step, we removed the osteosynthesis and implanted
a gentamicin and vancomycin loaded cement spacer (Figure
3). Swab examinations showed infection with a staphylococcus
lugdunensis, sensitive to vancomycin.
During the second revision the shoulder joint was
macroscopically free of infection, and thus an implantation of
an inverse shoulder prosthesis was done (Fa Synthes DePuy)
seven weeks later. During the operation the medullary canal was
filled with Cerament V using an extension tube (Figure 4a). In
addition, the stem of the prosthesis was augmented (Figure 4b)
and thereafter the prosthesis stem was press-fit inserted. A total
of 20 milliliters of Cerament V were used, in accordance with
the resistogram. Postoperatively, a dislocation of the prosthesis
components occurred. Therefore, at 2 months a proximal
enlargement of the stem with an augment was done (Figure 4c).
The microbiological samples taken during this surgery were
sterile after cultivation (Figure 4).
So far, there have been no adverse events regarding the use of
Cerament G or V as a surface coating during the follow up period.
First Case: Implant coating of a plate
15 months after the augmentation of the LCP with Cerament
G the tibia healed (Figure 1d), the patient is fully weight-bearing
without pain. He has a free range of motion in the adjacent joints
and no recurrence of the infection has been observed.
Second Case: Implant coating of a nail
No reinfection occurred 18 months after implantation of
the augmented nail-osteosynthesis. 3 months postoperatively
the patient could fully weight-bear the right leg with a slightly
limping gait remaining. At this time, he did not have pain in the
area of non-union and progressing, still incomplete bone healing
could be detected in the CT scan. 22 months after surgery a
complete bone healing was achieved. The patient is full weight
bearing without pain and a free range of motion in the adjacent
Third Case: Implant coating of a shoulder prosthesis
15 months after implant coating of the shoulder prosthesis
with Cerament V there were no signs for a recurrence of the
infection. The shoulder prosthesis was fully integrated. No
radiological signs of loosening were detected (Figure 4d). The
patient is painless but with limited range of motion (flexion 80°,
abduction 70°, external rotation 0°, free range of motion during
internal rotation and adduction).
We present a new surgical approach of an individual off-label
surface coating of plates, intramedullary nails or prostheses
and could show promising initial results in these cases. To
our knowledge this is a relevant innovation in the therapy of
fracture- and implant-associated infections. Most importantly
no adverse effects of the resorbable bone graft substitute were
observed and the osseo-integration of the plates, nails and the
prosthesis were observed. However, to gain further knowledge
on the osteoconductive- and anti-inflammatory effect of the
gentamicin- or vancomycin-loaded hydroxyapatite / calcium
sulphate bone graft substitutes, further investigations and
prospective clinical studies are required.
Ethics approval and consent to participate. This article does
only contain studies with anonymized data; therefore, after
inquiry with the ethics commission of the medical association of
Rhineland-Palatinate, no ethical approval was needed.
We declare that this manuscript is original, has not been
published before and is not currently being considered for
publication elsewhere. It has been read by all authors and each of the authors is convinced that the manuscript represents honest work.
HF and TG participated in the study design and surgeries,
analysis of the findings, and drafting of the final manuscript. GR
participated in the study design and surgeries. PAG, JA and LH
helped draft the final manuscript.