Skip to main content
Top
Published in: Journal of Orthopaedic Surgery and Research 1/2019

Open Access 01-12-2019 | Osteonecrosis of the Femoral Head | Research article

BMSC affinity peptide-functionalized β-tricalcium phosphate scaffolds promoting repair of osteonecrosis of the femoral head

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2019

Login to get access

Abstract

Background

Osteonecrosis of the femoral head (ONFH) is a disabling disease. Early treatment is crucial to the prognosis of the disease. Core decompression (CD) is one of the most commonly used methods for the treatment of early ONFH. But it could not prevent the collapse of the necrotic femoral head. How to improve the therapeutic effect of early ONFH on the basis of CD has become an area of focused research.

Methods

Functional β-tricalcium phosphate (β-TCP) scaffolds modified by DPIYALSWSGMA (DPI) peptide, a bone marrow-derived mesenchymal stem cell (BMSC) affinity peptide, were constructed using an adsorption/freeze-drying strategy. The affinity of DPI peptide towards rabbit BMSCs was investigated using flow cytometry and fluorescence cytochemistry. In vitro cell adhesion assay was performed to study the adherent ability of rabbit BMSCs on functional β-TCP scaffolds. After the rabbit model of early ONFH was established, DPI peptide-modified and pure β-TCP scaffolds were transplanted into the remaining cavity after CD. Meanwhile, rabbits treated with pure CD were used as blank control. Twelve weeks after surgery, histological analysis was performed to show the therapeutic effect of three methods on early ONFH.

Results

The result of ImageXpress Micro Confocal indicated that fabricated DPI peptide-modified functional β-TCP scaffolds exhibited green fluorescence. In flow cytometry, the average fluorescence intensity for rabbit BMSCs incubated with FITC-DPI was significantly higher than that of FITC-LSP (P = 2.733 × 10−8). In fluorescence cytochemistry, strong fluorescent signals were observed in rabbit BMSCs incubated with FITC-DPI and FITC-RGD, whereas no fluorescent signals in cells incubated with FITC-LSP. In cell adhesion assay, the number of adherent cells to β-TCP-DPI scaffolds was more than that of pure β-TCP scaffolds (P = 0.033). The CD + β-TCP-DPI group expressed the lowest vacant bone lacunae percentage compared to CD group (P = 2.350 × 10−4) and CD + β-TCP group (P = 0.020). The expression content of COL1 in CD + β-TCP-DPI group was much higher than CD group (P = 1.262 × 10−7) and CD + β-TCP group (P = 1.666 × 10−7) according to the integrated optical density (IOD) analyses.

Conclusion

Functional β-TCP scaffolds modified by DPI peptide were successfully synthesized using an adsorption/freeze-drying strategy. DPI peptide has good affinity towards rabbit BMSCs. The adhesion of rabbit BMSCs on DPI peptide-modified β-TCP scaffolds was apparently enhanced. CD followed by implantation of DPI peptide-modified β-TCP scaffolds can apparently improve the treatment of early ONFH compared with pure CD and CD followed by implantation of unmodified β-TCP scaffolds. Our current study provides an improved method for the treatment of early ONFH.
Literature
1.
go back to reference Petek D, Hannouche D, Suva D. Osteonecrosis of the femoral head: pathophysiology and current concepts of treatment. EFORT Open Rev. 2019;4:85–97.CrossRef Petek D, Hannouche D, Suva D. Osteonecrosis of the femoral head: pathophysiology and current concepts of treatment. EFORT Open Rev. 2019;4:85–97.CrossRef
2.
go back to reference Larson E, Jones LC, Goodman SB, Koo KH, Cui Q. Early-stage osteonecrosis of the femoral head: where are we and where are we going in year 2018? Int Orthop. 2018;42:1723–8.CrossRef Larson E, Jones LC, Goodman SB, Koo KH, Cui Q. Early-stage osteonecrosis of the femoral head: where are we and where are we going in year 2018? Int Orthop. 2018;42:1723–8.CrossRef
3.
go back to reference Moya-Angeler J, Gianakos AL, Villa JC, Ni A, Lane JM. Current concepts on osteonecrosis of the femoral head. World J Orthop. 2015;6:590–601.CrossRef Moya-Angeler J, Gianakos AL, Villa JC, Ni A, Lane JM. Current concepts on osteonecrosis of the femoral head. World J Orthop. 2015;6:590–601.CrossRef
4.
go back to reference Lieberman JR. Core decompression for osteonecrosis of the hip. Clin Orthop Relat Res. 2004;418:29–33.CrossRef Lieberman JR. Core decompression for osteonecrosis of the hip. Clin Orthop Relat Res. 2004;418:29–33.CrossRef
5.
go back to reference Levasseur R. Mechanisms of osteonecrosis. Joint Bone Spine. 2008;75:639–42.CrossRef Levasseur R. Mechanisms of osteonecrosis. Joint Bone Spine. 2008;75:639–42.CrossRef
6.
go back to reference Cohen-Rosenblum A, Cui Q. Osteonecrosis of the femoral head. Orthop Clin North Am. 2019;50:139–49.CrossRef Cohen-Rosenblum A, Cui Q. Osteonecrosis of the femoral head. Orthop Clin North Am. 2019;50:139–49.CrossRef
7.
go back to reference Koo KH, Kim R, Ko GH, Song HR, Jeong ST, Cho SH. Preventing collapse in early osteonecrosis of the femoral head. A randomised clinical trial of core decompression. J Bone Joint Surg Br. 1995;77:870–4.CrossRef Koo KH, Kim R, Ko GH, Song HR, Jeong ST, Cho SH. Preventing collapse in early osteonecrosis of the femoral head. A randomised clinical trial of core decompression. J Bone Joint Surg Br. 1995;77:870–4.CrossRef
8.
go back to reference Kawate K, Yajima H, Ohgushi H, Kotobuki N, Sugimoto K, Ohmura T, et al. Tissue-engineered approach for the treatment of steroid-induced osteonecrosis of the femoral head: transplantation of autologous mesenchymal stem cells cultured with beta-tricalcium phosphate ceramics and free vascularized fibula. Artif Organs. 2006;30:960–2.CrossRef Kawate K, Yajima H, Ohgushi H, Kotobuki N, Sugimoto K, Ohmura T, et al. Tissue-engineered approach for the treatment of steroid-induced osteonecrosis of the femoral head: transplantation of autologous mesenchymal stem cells cultured with beta-tricalcium phosphate ceramics and free vascularized fibula. Artif Organs. 2006;30:960–2.CrossRef
9.
go back to reference Liu ZH, Guo WS, Li ZR, Cheng LM, Zhang QD, Yue DB, et al. Porous tantalum rods for treating osteonecrosis of the femoral head. Genet Mol Res. 2014;13:8342–52.CrossRef Liu ZH, Guo WS, Li ZR, Cheng LM, Zhang QD, Yue DB, et al. Porous tantalum rods for treating osteonecrosis of the femoral head. Genet Mol Res. 2014;13:8342–52.CrossRef
10.
go back to reference Jiang HJ, Huang XJ, Tan YC, Liu DZ, Wang L. Core decompression and implantation of calcium phosphate cement/danshen drug delivery system for treating ischemic necrosis of femoral head at stages I, II and III of antigen reactive cell opsonization. Chin J Traumatol. 2009;12:285–90.PubMed Jiang HJ, Huang XJ, Tan YC, Liu DZ, Wang L. Core decompression and implantation of calcium phosphate cement/danshen drug delivery system for treating ischemic necrosis of femoral head at stages I, II and III of antigen reactive cell opsonization. Chin J Traumatol. 2009;12:285–90.PubMed
11.
go back to reference Ng AM, Tan KK, Phang MY, Aziyati O, Tan GH, Isa MR, et al. Differential osteogenic activity of osteoprogenitor cells on HA and TCP/HA scaffold of tissue engineered bone. J Biomed Mater Res A. 2008;85:301–12.CrossRef Ng AM, Tan KK, Phang MY, Aziyati O, Tan GH, Isa MR, et al. Differential osteogenic activity of osteoprogenitor cells on HA and TCP/HA scaffold of tissue engineered bone. J Biomed Mater Res A. 2008;85:301–12.CrossRef
12.
go back to reference Suh DY, Boden SD, Louis-Ugbo J, Mayr M, Murakami H, Kim HS, et al. Delivery of recombinant human bone morphogenetic protein-2 using a compression-resistant matrix in posterolateral spine fusion in the rabbit and in the non-human primate. Spine. 2002;27:353–60.CrossRef Suh DY, Boden SD, Louis-Ugbo J, Mayr M, Murakami H, Kim HS, et al. Delivery of recombinant human bone morphogenetic protein-2 using a compression-resistant matrix in posterolateral spine fusion in the rabbit and in the non-human primate. Spine. 2002;27:353–60.CrossRef
13.
go back to reference Tang TT, Lu B, Yue B, Xie XH, Xie YZ, Dai KR, et al. Treatment of osteonecrosis of the femoral head with hBMP-2-gene-modified tissue-engineered bone in goats. J Bone Joint Surg Br. 2007;89:127–9.CrossRef Tang TT, Lu B, Yue B, Xie XH, Xie YZ, Dai KR, et al. Treatment of osteonecrosis of the femoral head with hBMP-2-gene-modified tissue-engineered bone in goats. J Bone Joint Surg Br. 2007;89:127–9.CrossRef
14.
go back to reference Aoyama T, Goto K, Kakinoki R, Ueda M, Kasai Y, Maekawa T, et al. An exploratory clinical trial for idiopathic osteonecrosis of femoral head by cultured autologous multipotent mesenchymal stromal cells augmented with vascularized bone grafts. Tissue Eng Part B Rev. 2014;20:233–42.CrossRef Aoyama T, Goto K, Kakinoki R, Ueda M, Kasai Y, Maekawa T, et al. An exploratory clinical trial for idiopathic osteonecrosis of femoral head by cultured autologous multipotent mesenchymal stromal cells augmented with vascularized bone grafts. Tissue Eng Part B Rev. 2014;20:233–42.CrossRef
15.
go back to reference Alvarez LM, Rivera JJ, Stockdale L, Saini S, Lee RT, Griffith LG. Tethering of epidermal growth factor (EGF) to beta tricalcium phosphate (βTCP) via fusion to a high affinity, multimeric βTCP-binding peptide: effects on human multipotent stromal cells/connective tissue progenitors. PLoS One. 2015;10:e0129600.CrossRef Alvarez LM, Rivera JJ, Stockdale L, Saini S, Lee RT, Griffith LG. Tethering of epidermal growth factor (EGF) to beta tricalcium phosphate (βTCP) via fusion to a high affinity, multimeric βTCP-binding peptide: effects on human multipotent stromal cells/connective tissue progenitors. PLoS One. 2015;10:e0129600.CrossRef
16.
go back to reference Sahmani S, Samandari SS, Shahali M, Joneidi Yekta H, Aghadavoudi F, Montazeran AH, et al. Mechanical and biological performance of axially loaded novel bio-nanocomposite sandwich plate-type implant coated by biological polymer thin film. J Mech Behav Biomed Mater. 2018;88:238–50.CrossRef Sahmani S, Samandari SS, Shahali M, Joneidi Yekta H, Aghadavoudi F, Montazeran AH, et al. Mechanical and biological performance of axially loaded novel bio-nanocomposite sandwich plate-type implant coated by biological polymer thin film. J Mech Behav Biomed Mater. 2018;88:238–50.CrossRef
17.
go back to reference Meng Q, Man Z, Dai L, Huang H, Zhang X, Hu X, et al. A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration. Sci Rep. 2015;5:17802.CrossRef Meng Q, Man Z, Dai L, Huang H, Zhang X, Hu X, et al. A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration. Sci Rep. 2015;5:17802.CrossRef
18.
go back to reference Hernigou P, Flouzat-Lachaniette CH, Delambre J, Poignard A, Allain J, Chevallier N, et al. Osteonecrosis repair with bone marrow cell therapies: state of the clinical art. Bone. 2015;70:102–9.CrossRef Hernigou P, Flouzat-Lachaniette CH, Delambre J, Poignard A, Allain J, Chevallier N, et al. Osteonecrosis repair with bone marrow cell therapies: state of the clinical art. Bone. 2015;70:102–9.CrossRef
19.
go back to reference Ramaraju H, Miller SJ, Kohn DH. Dual-functioning peptides discovered by phage display increase the magnitude and specificity of BMSC attachment to mineralized biomaterials. Biomaterials. 2017;134:1–12.CrossRef Ramaraju H, Miller SJ, Kohn DH. Dual-functioning peptides discovered by phage display increase the magnitude and specificity of BMSC attachment to mineralized biomaterials. Biomaterials. 2017;134:1–12.CrossRef
20.
go back to reference Wang GZ, Man ZT, Xin H, Li Y, Wu CS, Sun S. Enhanced adhesion and proliferation of bone marrow mesenchymal stem cells on β-tricalcium phosphate modified by an affinity peptide. Mol Med Rep. 2019;19:375–81.PubMed Wang GZ, Man ZT, Xin H, Li Y, Wu CS, Sun S. Enhanced adhesion and proliferation of bone marrow mesenchymal stem cells on β-tricalcium phosphate modified by an affinity peptide. Mol Med Rep. 2019;19:375–81.PubMed
21.
go back to reference Zhang HX, Zhang XP, Xiao GY, Hou Y, Cheng L, Si M, et al. In vitro and in vivo evaluation of calcium phosphate composite scaffolds containing BMP-VEGF loaded PLGA microspheres for the treatment of avascular necrosis of the femoral head. Mater Sci Eng C Mater Biol Appl. 2016;60:298–307.CrossRef Zhang HX, Zhang XP, Xiao GY, Hou Y, Cheng L, Si M, et al. In vitro and in vivo evaluation of calcium phosphate composite scaffolds containing BMP-VEGF loaded PLGA microspheres for the treatment of avascular necrosis of the femoral head. Mater Sci Eng C Mater Biol Appl. 2016;60:298–307.CrossRef
22.
go back to reference Qin L, Zhang G, Sheng H, Yeung KW, Yeung HY, Chan CW, et al. Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone. Bone. 2006;39:863–71.CrossRef Qin L, Zhang G, Sheng H, Yeung KW, Yeung HY, Chan CW, et al. Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone. Bone. 2006;39:863–71.CrossRef
23.
go back to reference Wang GJ, Dughman SS, Reger SI, Stamp WG. The effect of core decompression on femoral head blood flow in steroid-induced avascular necrosis of the femoral head. J Bone Joint Surg Am. 1985;67:121–4.CrossRef Wang GJ, Dughman SS, Reger SI, Stamp WG. The effect of core decompression on femoral head blood flow in steroid-induced avascular necrosis of the femoral head. J Bone Joint Surg Am. 1985;67:121–4.CrossRef
24.
go back to reference Mont MA, Carbone JJ, Fairbank AC. Core decompression versus nonoperative management for osteonecrosis of the hip. Clin Orthop Relat Res. 1996;324:169–78.CrossRef Mont MA, Carbone JJ, Fairbank AC. Core decompression versus nonoperative management for osteonecrosis of the hip. Clin Orthop Relat Res. 1996;324:169–78.CrossRef
25.
go back to reference Mont MA, Cherian JJ, Sierra RJ, Jones LC, Lieberman JR. Nontraumatic osteonecrosis of the femoral head: where do we stand today? A ten-year update. J Bone Joint Surg Am. 2015;97:1604–27.CrossRef Mont MA, Cherian JJ, Sierra RJ, Jones LC, Lieberman JR. Nontraumatic osteonecrosis of the femoral head: where do we stand today? A ten-year update. J Bone Joint Surg Am. 2015;97:1604–27.CrossRef
26.
go back to reference Zalavras CG, Lieberman JR. Osteonecrosis of the femoral head: evaluation and treatment. J Am Acad Orthop Surg. 2014;22:455–64.CrossRef Zalavras CG, Lieberman JR. Osteonecrosis of the femoral head: evaluation and treatment. J Am Acad Orthop Surg. 2014;22:455–64.CrossRef
27.
go back to reference Sahmani S, Khandan A, Samandari SS, Aghdam MM. Nonlinear bending and instability analysis of bioceramics composed with magnetite nanoparticles: fabrication, characterization, and simulation. Ceram Int. 2018;44:9540–9.CrossRef Sahmani S, Khandan A, Samandari SS, Aghdam MM. Nonlinear bending and instability analysis of bioceramics composed with magnetite nanoparticles: fabrication, characterization, and simulation. Ceram Int. 2018;44:9540–9.CrossRef
28.
go back to reference Sahmani S, Khandan A, Samandari SS, Aghdam MM. Vibrations of beam-type implants made of 3D printed bredigite-magnetite bio-nanocomposite scaffolds under axial compression: application, communication and simulation. Ceram Int. 2018;44:11282–91.CrossRef Sahmani S, Khandan A, Samandari SS, Aghdam MM. Vibrations of beam-type implants made of 3D printed bredigite-magnetite bio-nanocomposite scaffolds under axial compression: application, communication and simulation. Ceram Int. 2018;44:11282–91.CrossRef
29.
go back to reference Yang P, Bian C, Huang X, Shi A, Wang C, Wang K. Core decompression in combination with nano-hydroxyapatite/polyamide 66 rod for the treatment of osteonecrosis of the femoral head. Arch Orthop Trauma Surg. 2014;134:103–12.CrossRef Yang P, Bian C, Huang X, Shi A, Wang C, Wang K. Core decompression in combination with nano-hydroxyapatite/polyamide 66 rod for the treatment of osteonecrosis of the femoral head. Arch Orthop Trauma Surg. 2014;134:103–12.CrossRef
30.
go back to reference Landgraeber S, Warwas S, Claßen T, Jäger M. Modifications to advanced core decompression for treatment of avascular necrosis of the femoral head. BMC Musculoskelet Disord. 2017;18:479.CrossRef Landgraeber S, Warwas S, Claßen T, Jäger M. Modifications to advanced core decompression for treatment of avascular necrosis of the femoral head. BMC Musculoskelet Disord. 2017;18:479.CrossRef
31.
go back to reference Shamsoddin E, Houshmand B, Golabgiran M. Biomaterial selection for bone augmentation in implant dentistry: a systematic review. J Adv Pharm Technol Res. 2019;10:46–50.CrossRef Shamsoddin E, Houshmand B, Golabgiran M. Biomaterial selection for bone augmentation in implant dentistry: a systematic review. J Adv Pharm Technol Res. 2019;10:46–50.CrossRef
32.
go back to reference Liu B, Lun DX. Current application of β-tricalcium phosphate composites in orthopaedics. Orthop Surg. 2012;4:139–44.CrossRef Liu B, Lun DX. Current application of β-tricalcium phosphate composites in orthopaedics. Orthop Surg. 2012;4:139–44.CrossRef
33.
go back to reference 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;43:234–9.CrossRef 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;43:234–9.CrossRef
34.
go back to reference Tatara AM, Mikos AG. Tissue engineering in orthopaedics. J Bone Joint Surg Am. 2016;98:1132–9.CrossRef Tatara AM, Mikos AG. Tissue engineering in orthopaedics. J Bone Joint Surg Am. 2016;98:1132–9.CrossRef
35.
go back to reference Joneidi Yekta H, Shahali M, Khorshidi S, Rezaei S, Montazeran AH, Samandari SS, et al. Mathematically and experimentally defined porous bone scaffold produced for bone substitute application. Nanomed J. 2018;5:227–34. Joneidi Yekta H, Shahali M, Khorshidi S, Rezaei S, Montazeran AH, Samandari SS, et al. Mathematically and experimentally defined porous bone scaffold produced for bone substitute application. Nanomed J. 2018;5:227–34.
36.
go back to reference Yamamoto T, Irisa T, Sugioka Y, Sueishi K. Effects of pulse methylprednisolone on bone and marrow tissues: corticosteroid-induced osteonecrosis in rabbits. Arthritis Rheum. 1997;40:2055–64.CrossRef Yamamoto T, Irisa T, Sugioka Y, Sueishi K. Effects of pulse methylprednisolone on bone and marrow tissues: corticosteroid-induced osteonecrosis in rabbits. Arthritis Rheum. 1997;40:2055–64.CrossRef
37.
go back to reference Ficat RP. Idiopathic bone necrosis of the femoral head. Early diagnosis and treatment. J Bone Joint Surg Br. 1985;67:3–9.CrossRef Ficat RP. Idiopathic bone necrosis of the femoral head. Early diagnosis and treatment. J Bone Joint Surg Br. 1985;67:3–9.CrossRef
38.
go back to reference Gangji V, Hauzeur JP. Treating osteonecrosis with autologous bone marrow cells. Skelet Radiol. 2010;39:209–11.CrossRef Gangji V, Hauzeur JP. Treating osteonecrosis with autologous bone marrow cells. Skelet Radiol. 2010;39:209–11.CrossRef
Metadata
Title
BMSC affinity peptide-functionalized β-tricalcium phosphate scaffolds promoting repair of osteonecrosis of the femoral head
Publication date
01-12-2019
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2019
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-019-1243-5

Other articles of this Issue 1/2019

Journal of Orthopaedic Surgery and Research 1/2019 Go to the issue