Abstract
Background
Masquelet technique is a two-stage surgical procedure used in the treatment of critical-size
bone defects (CSD). Adding antibiotics to polymethylmethacrylate (PMMA) is still questionable
to create higher quality induced membrane (IM). The aim of the study was to evaluate
the effects of three antibiotic-supplemented cement, fusidic acid, teicoplanin, and
gentamicin, on osteogenesis and IM progression applied to rat femur CSD model by comparing
histopathological, biochemical, and immunohistochemical findings.
Methods
Twenty-eight male rats were divided into four groups control, gentamicin (G), teicoplanin
(T), and fusidic acid (FA). A 10 mm CSD was created in rat femurs. In the postoperative
4th week, intracardiac blood samples were collected for biochemical analysis of bone
alkaline phosphatase (BALP), osteocalcin (OC), and tumor necrosis factor-alpha (TNF-α)
levels. IMs obtained in secondary operation were fixed and prepared for histopathological
scoring of membrane progression and immunohistochemical evaluation of rat-specific
Transforming Growth Factor-Beta (TGF-β), Runt-related Transcription Factor 2 (Runx2),
and Vascular Endothelial Growth Factor (VEGF) expressions.
Results
Levels of BALP and OC in serum didn't change among groups significantly while serum
TNF-α levels significantly decreased in all antibiotic groups compared to the control
group (P = 0.017). Histological scores of groups FA and T were significantly higher than those
of groups Control and G (P = 0.0007). IMs of groups T and FA showed good progression while those of groups Control
and G were also moderately progressed. A significant increase in TGF-β expression
was observed in group G and FA (P = 0.001) while a significant increase in the expression of VEGF was observed in groups
G and T compared to the control group (P = 0.036).
Conclusions
The bone cement impregnated with thermostable and safe antibiotics, gentamicin, fusidic
acid, and teicoplanin can increase osteogenesis and support IM progression by increasing
the expressions of TGF-β and VEGF. Anabolic effects of induced membranes used in the
treatment of critical-size bone defects can be enhanced by antibiotic-supplemented
PMMAs applied by altering the original technique.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to InjuryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Induced membrane technique: pearls and pitfalls.J Orthop Trauma. 2017; 31 (Suppl): S36-S38
- The induced membrane technique.Orthop Traumatol Surg Res. 2020; 106: 785-787
- Restoration of long bone defects treated with the induced membrane technique: Protocol and outcomes.Injury. 2016; 47: S53-S61
- Establishment and characterization of the Masquelet induced membrane technique in a rat femur critical-sized defect model.J Tissue Eng Regen Med. 2016; 10: E382-E396
- Masquelet technique for the treatment of segmental bone loss have we made any progress?.Injury. 2016; 47: 2051-2052
- Alteration of Masquelet's induced membrane characteristics by different kinds of antibiotic enriched bone cement in a critical size defect model in the rat's femur.Injury. 2016; 47: 325-334
- The induced membrane technique for the management of long bone defects.Bone Jt J. 2020; 102-B: 1723-1734
- The induced membrane technique for the management of segmental tibial defect or nonunion: a systematic review and meta-analysis.Biomed Res Int. 2020; 20205893642
- [Application of membrane induced by antibiotic-loaded bone cement in skin grafting for tendon exposed wound healing].Zhongguo Gu Shang. 2020; 33: 564-566https://doi.org/10.12200/j.issn.1003-0034.2020.06.015
- The induced membrane technique in animal models: a systematic review.OTA Int. 2022; 5: e176https://doi.org/10.1097/OI9.0000000000000176
- The 3Rs and Humane Experimental Technique: Implementing Change.Animals (Basel). 2019 Sep 30; 9: 754https://doi.org/10.3390/ani9100754
- The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats.J Orthop Res. 1991; 9: 383-390
- The effects of alpha-lipoic acid on liver cells are damages and apoptosis induced by polyunsaturated fatty acids.Food Chem Toxicol. 2013; 53: 84-93
- Resveratrol can prevent CCl₄-induced liver injury by inhibiting Notch signaling pathway.Histol Histopathol. 2016; 31: 769-784
- Bone defect treatment: does the type and properties of the spacer affect the induction of Masquelet membrane? Evidence today.Eur J Trauma Emerg Surg. 2022; https://doi.org/10.1007/s00068-022-02005-x
- Masquelet technique: effects of vancomycin concentration on quality of the induced membrane.Injury. 2022; 53: 868-877
- The effect of surgical technique and spacer texture on bone regeneration: a caprine study using the masquelet technique.Clin Orthop Relat Res. 2017; 475: 2575-2585
- The Masquelet technique: current concepts, animal models, and perspectives.J Tissue Eng Regen Med. 2020; 14: 1349-1359
- The Masquelet technique: can disposable polypropylene syringes be an alternative to standard PMMA spacers? A rat bone defect model.Clin Orthop Relat Res. 2021; 479: 2737-2751
- The Masquelet technique for membrane induction and the healing of ovine critical-sized segmental defects.PLoS One. 2014; 9 (e114122)https://doi.org/10.1371/journal.pone.0114122
- Histological analysis of induced membranes in patients whose bone defects were treated with the Masquelet technique to identify factors affecting the vascularity of induced membranes.J Orthop Surg Res. 2021; 16: 248
- Size matters: defining critical in bone defect size!.J Orthop Trauma. 2017; 31 (Suppl): S20-S22
- New approaches in the treatment of critical-size segmental defects in long bones.MacromoL Symp. 2007; 253: 147-161
- Antibiotic-loaded polymethylmethacrylate beads and spacers in treatment of orthopedic infections and the role of biofilm formation.Front Microbiol. 2019; 10: 1626
- Bone repair using the masquelet technique.J Bone Jt Surg Am. 2019; 101: 1024-1036
- Is the bioactivity of induced membranes time dependent?.Eur J Trauma Emerg Surg. 2022; 48: 3051-3061https://doi.org/10.1007/s00068-021-01844-4
- Vascular endothelial growth factor (VEGF) and its receptors.FASEB J. 1999; 13: 9-22
- Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover.Proc Natl Acad Sci USA. 2002; 99: 9656-9661
- Expression of vascular endothelial growth factors and their receptors during osteoblast differentiation.Endocrinology. 2000; 141: 1667-1674
- Masquelet technique for treatment of posttraumatic bone defects.Sci World J. 2014; 2014710302
- The comparative efficacy and safety of teicoplanin and vancomycin.J Antimicrob Chemother. 1996; 37: 209-222
- Fusidic acid: a bacterial elongation factor inhibitor for the oral treatment of acute and chronic staphylococcal infections.Cold Spring Harb Perspect Med. 2016; 6a025437
- Fusidic acid in vitro activity.Int J Antimicrob Agents. 1999; 12 (Suppl): S45-S58
- Antibiotic prophylaxis in orthopaedic surgery: difficult decisions in an era of evolving antibiotic resistance.Bone Jt J. 2016; 98-B: 1014-1019
- Evaluation of antibiotic resistance to orally administrable antibiotics in staphylococcal bone and joint infections in one of the largest university hospitals in Germany: is there a role for fusidic acid?.Int J Antimicrob Agents. 2016; 47: 155-157
- Stability kinetics of fusidic acid: Development and validation of stability indicating analytical method by employing analytical quality by design approach in medicinal product(s).J Chromatogr B Anal Technol Biomed Life Sci. 2019; 1120: 113-124
- Gentamicin-loaded bone cement with clindamycin or fusidic acid added: biofilm formation and antibiotic release.J Biomed Mater Res A. 2005; 73: 165-170
- Levels of fusidic acid in skin blister fluid and serum after repeated administration of two dosages (250 and 500 mg).Br J Dermatol. 1992; 126: 591-595
- A reappraisal of its antimicrobial activity, pharmacokinetic properties, and therapeutic efficacy.Drugs. 1994; 47: 823-854
- The effect of teicoplanin on fracture healing: an experimental study.Eklem Hastalik Cerrahisi. 2016; 27: 16-21
- Mechanical strength of antibiotic-loaded bone cement: A biomechanical study with Cemex bone cement, teicoplanin, and tobramycin.Acta Orthop Traumatol Turc. 1997; 31: 245-249
- [Mechanical strength of antibiotic-impregnated bone cement on Day 0 and Day 15: a biomechanical study with Surgical Simplex P and teicoplanin].Acta Orthop Traumatol Turc. 2002; 36: 63-71
- Masquelet technique for the treatment of bone defects: tips-tricks and future directions.Injury. 2011; 42: 591-598
- The mechanism of action of induced membranes in bone repair.J Bone Jt Surg. 2013; 95: 597-604
- Antibiotic-loaded bone cement for infection prophylaxis in total joint replacement.J Bone Jt Surg Am. 2006; 88: 2487-2500
- Elution characteristics of vancomycin and tobramycin combined in acrylic bone-cement.J Arthroplasty. 1996; 11: 939-944https://doi.org/10.1016/s0883-5403(96)80135-5
- Results of the Induced Membrane Technique in the Management of Traumatic Bone Loss in the Lower Limb: A Cohort Study.J Orthop Trauma. 2019; 33: 131-136
- Possibility of one-stage surgery to reconstruct bone defects using the modified Masquelet technique with degradable calcium sulfate as a cement spacer: A case report and hypothesis.Biomed Rep. 2016; 4: 374-378
- Calcium sulfate induced versus PMMA-induced membrane in a critical-sized femoral defect in a rat model.Sci Rep. 2018; 8 (Published 2018 Jan 12): 637
- Reconstruction of large segmental bone defects in rabbit using the Masquelet technique with α-calcium sulfate hemihydrate.J Orthop Surg Res. 2019; 14 (Published 2019 Jun 26): 192
Article info
Publication history
Published online: October 26, 2022
Accepted:
October 24,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
