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Published in: Journal of Bone and Mineral Metabolism 6/2019

01-11-2019 | Bone Defect | Original Article

Local administration of aspirin with β-tricalcium phosphate/poly-lactic-co-glycolic acid (β-TCP/PLGA) could enhance osteoporotic bone regeneration

Authors: Zhou-Shan Tao, Xing-Jing Wu, Wan-Shu Zhou, Xin-ju Wu, Wei Liao, Min Yang, Hong-Guang Xu, Lei Yang

Published in: Journal of Bone and Mineral Metabolism | Issue 6/2019

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Abstract

Composite materials β-tricalcium phosphate (β-TCP) and poly-lactic-co-glycolic acid (PLGA) have achieved stable bone regeneration without cell transplantation in previous studies. Recent research shows that aspirin (ASP) has great potential in promoting bone regeneration. The objective of the present study was to incorporate PLGA into β-TCP combined with a lower single-dose local administration of ASP to enhance its in vivo biodegradation and bone tissue growth. After the creation of a rodent critical-sized femoral metaphyseal bone defect, PLGA -modified β-TCP (TP) was prepared by mixing sieved granules of β-TCP and PLGA (50:50, v/v) for medical use, then TP with dripped 50 µg/0.1 ml and 100 µg/0.1 ml aspirin solution was implanted into the defect of OVX rats until death at 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, biomechanics and real time RT-PCR. The results of our study show that a single-dose local administration of ASP combined with the local usage of TP can increase the healing of defects in OVX rats. Single-dose local administration of aspirin can improve the transcription of genes involved in the regulation of bone formation and vascularization in the defect area, and inhibits osteoclast activity. Furthermore, treatments with a higher single-dose local administration of ASP and TP showed a stronger effect on accelerating the local bone formation than while using a lower dose of ASP. The results from our study demonstrate that the combination of a single-dose local administration of ASP and β-TCP/PLGA had an additive effect on local bone formation in osteoporosis rats, and bone regeneration by PLGA/β-TCP/ASP occured in a dose-dependent manner.
Literature
1.
go back to reference Boulier A, Schwarz J, Lespesailles E, Baniel A, Tomé D, Blais A (2017) Combination of micellar casein with calcium and vitamins D2 and K2 improves bone status of ovariectomized mice. Osteoporos Int 27:1–10 Boulier A, Schwarz J, Lespesailles E, Baniel A, Tomé D, Blais A (2017) Combination of micellar casein with calcium and vitamins D2 and K2 improves bone status of ovariectomized mice. Osteoporos Int 27:1–10
2.
go back to reference Hernández A, Sánchez E, Soriano I, Reyes R, Delgado A, Évora C (2012) Material-related effects of BMP-2 delivery systems on bone regeneration. Acta Biomater 8:781–791CrossRef Hernández A, Sánchez E, Soriano I, Reyes R, Delgado A, Évora C (2012) Material-related effects of BMP-2 delivery systems on bone regeneration. Acta Biomater 8:781–791CrossRef
3.
go back to reference Thormann U, Ray S, Sommer U, Elkhassawna T, Rehling T, Hundgeburth M, Henß A, Rohnke M, Janek J, Lips KS, Heiss C, Schlewitz G, Szalay G, Schumacher M, Gelinsky M, Schnettler R, Alt V (2013) Bone formation induced by strontium modified calcium phosphate cement in critical-size metaphyseal fracture defects in ovariectomized rats. Biomaterials 34:8589–8598CrossRef Thormann U, Ray S, Sommer U, Elkhassawna T, Rehling T, Hundgeburth M, Henß A, Rohnke M, Janek J, Lips KS, Heiss C, Schlewitz G, Szalay G, Schumacher M, Gelinsky M, Schnettler R, Alt V (2013) Bone formation induced by strontium modified calcium phosphate cement in critical-size metaphyseal fracture defects in ovariectomized rats. Biomaterials 34:8589–8598CrossRef
4.
go back to reference Sengupta S, Park SH, Patel A, Carn J, Lee K, Kaplan DLJTEPA (2010) Hypoxia and amino acid supplementation synergistically promote the osteogenesis of human mesenchymal stem cells on silk protein scaffolds. Tissue Eng Part A 16:3623CrossRef Sengupta S, Park SH, Patel A, Carn J, Lee K, Kaplan DLJTEPA (2010) Hypoxia and amino acid supplementation synergistically promote the osteogenesis of human mesenchymal stem cells on silk protein scaffolds. Tissue Eng Part A 16:3623CrossRef
5.
go back to reference Denry I, Kuhn LT (2016) Design and characterization of calcium phosphate ceramic scaffolds for bone tissue engineering. Dent Mater 32:43–53CrossRef Denry I, Kuhn LT (2016) Design and characterization of calcium phosphate ceramic scaffolds for bone tissue engineering. Dent Mater 32:43–53CrossRef
6.
go back to reference Bose S, Roy M, Bandyopadhyay A (2012) Recent advances in bone tissue engineering scaffolds. Trends Biotechnol 30:546–554CrossRef Bose S, Roy M, Bandyopadhyay A (2012) Recent advances in bone tissue engineering scaffolds. Trends Biotechnol 30:546–554CrossRef
7.
go back to reference Shavandi A, Ael-D B, Sun Z, Ali A, Gould MJMS (2015) A novel squid pen chitosan/hydroxyapatite/β-tricalcium phosphate composite for bone tissue engineering. Mater Sci Eng C 55:373–383CrossRef Shavandi A, Ael-D B, Sun Z, Ali A, Gould MJMS (2015) A novel squid pen chitosan/hydroxyapatite/β-tricalcium phosphate composite for bone tissue engineering. Mater Sci Eng C 55:373–383CrossRef
8.
go back to reference Liu X, Ma PXJAoBE (2004) Polymeric scaffolds for bone tissue engineering. Ann Biomed Eng 32:477–486CrossRef Liu X, Ma PXJAoBE (2004) Polymeric scaffolds for bone tissue engineering. Ann Biomed Eng 32:477–486CrossRef
9.
go back to reference Purnama A, Aid-Launais R, Haddad O, Maire M, Mantovani D, Letourneur D, Hlawaty H, Le Visage C (2015) Fucoidan in a 3D scaffold interacts with vascular endothelial growth factor and promotes neovascularization in mice. Drug Deliv Transl Res 5(2):187–197CrossRef Purnama A, Aid-Launais R, Haddad O, Maire M, Mantovani D, Letourneur D, Hlawaty H, Le Visage C (2015) Fucoidan in a 3D scaffold interacts with vascular endothelial growth factor and promotes neovascularization in mice. Drug Deliv Transl Res 5(2):187–197CrossRef
10.
go back to reference Zeng YP, Yang C, Li Y, Fan Y, Yang HJ, Liu B, Sang HX (2016) Aspirin inhibits osteoclastogenesis by suppressing the activation of NF-κB and MAPKs in RANKL-induced RAW264.7 cells. Mol Med Rep 14:1957–1962CrossRef Zeng YP, Yang C, Li Y, Fan Y, Yang HJ, Liu B, Sang HX (2016) Aspirin inhibits osteoclastogenesis by suppressing the activation of NF-κB and MAPKs in RANKL-induced RAW264.7 cells. Mol Med Rep 14:1957–1962CrossRef
11.
go back to reference Liu Y, Wang L, Kikuiri T, Akiyama K, Chen C, Xu X, Yang R, Chen W, Wang S, Shi S (2011) Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α. Nat Med 17(12):1594–1601CrossRef Liu Y, Wang L, Kikuiri T, Akiyama K, Chen C, Xu X, Yang R, Chen W, Wang S, Shi S (2011) Mesenchymal stem cell-based tissue regeneration is governed by recipient T lymphocytes via IFN-γ and TNF-α. Nat Med 17(12):1594–1601CrossRef
12.
go back to reference Wei J, Wang J, Gong Y, Zeng R (2015) Effectiveness of combined salmon calcitonin and aspirin therapy for osteoporosis in ovariectomized rats. Mol Med Rep 12:1717CrossRef Wei J, Wang J, Gong Y, Zeng R (2015) Effectiveness of combined salmon calcitonin and aspirin therapy for osteoporosis in ovariectomized rats. Mol Med Rep 12:1717CrossRef
13.
go back to reference Zhang HX, Xiao GY, Wang X, Dong ZG, Ma ZY, Li L, Li YH, Pan X, Nie L (2015) Biocompatibility and osteogenesis of calcium phosphate composite scaffolds containing simvastatin-loaded PLGA microspheres for bone tissue engineering. J Biomed Mater Res Part A 103:3250–3258CrossRef Zhang HX, Xiao GY, Wang X, Dong ZG, Ma ZY, Li L, Li YH, Pan X, Nie L (2015) Biocompatibility and osteogenesis of calcium phosphate composite scaffolds containing simvastatin-loaded PLGA microspheres for bone tissue engineering. J Biomed Mater Res Part A 103:3250–3258CrossRef
14.
go back to reference Tao ZS, Zhou WS, Qiang Z, Tu KK, Huang ZL, Xu HM, Sun T, Lv YX, Cui W, Yang L (2016) Intermittent administration of human parathyroid hormone (1–34) increases fixation of strontium-doped hydroxyapatite coating titanium implants via electrochemical deposition in ovariectomized rat femur. J Biomater Appl 30(7):952–960CrossRef Tao ZS, Zhou WS, Qiang Z, Tu KK, Huang ZL, Xu HM, Sun T, Lv YX, Cui W, Yang L (2016) Intermittent administration of human parathyroid hormone (1–34) increases fixation of strontium-doped hydroxyapatite coating titanium implants via electrochemical deposition in ovariectomized rat femur. J Biomater Appl 30(7):952–960CrossRef
18.
go back to reference Kajii F, Iwai A, Tanaka H, Matsui K, Kawai T, Kamakura S (2018) Single-dose local administration of teriparatide with a octacalcium phosphate collagen composite enhances bone regeneration in a rodent critical-sized calvarial defect. J Biomed Mater Res Part B Appl Biomater 106:1851–1857CrossRef Kajii F, Iwai A, Tanaka H, Matsui K, Kawai T, Kamakura S (2018) Single-dose local administration of teriparatide with a octacalcium phosphate collagen composite enhances bone regeneration in a rodent critical-sized calvarial defect. J Biomed Mater Res Part B Appl Biomater 106:1851–1857CrossRef
19.
go back to reference Tao ZS, Tu KK, Huang ZL, Zhou Q, Sun T, Xu HM, Zhou YL, Lv YX, Cui W, Yang L (2016) Combined treatment with parathyroid hormone (1–34) and beta-tricalcium phosphate had an additive effect on local bone formation in a rat defect model. Med Biol Eng Comput 54(9):1353–1362CrossRef Tao ZS, Tu KK, Huang ZL, Zhou Q, Sun T, Xu HM, Zhou YL, Lv YX, Cui W, Yang L (2016) Combined treatment with parathyroid hormone (1–34) and beta-tricalcium phosphate had an additive effect on local bone formation in a rat defect model. Med Biol Eng Comput 54(9):1353–1362CrossRef
22.
go back to reference Tao ZS, Lv YX, Cui W, Huang ZL, Tu KK, Zhou Q, Sun T, Yang L (2016) Effect of teriparatide on repair of femoral metaphyseal defect in ovariectomized rats. Z Gerontol Geriatr 49(5):423–428CrossRef Tao ZS, Lv YX, Cui W, Huang ZL, Tu KK, Zhou Q, Sun T, Yang L (2016) Effect of teriparatide on repair of femoral metaphyseal defect in ovariectomized rats. Z Gerontol Geriatr 49(5):423–428CrossRef
23.
go back to reference Yang N, Cui Y, Tan J, Fu X, Han X, Leng H, Song C (2014) Local injection of a single dose of simvastatin augments osteoporotic bone mass in ovariectomized rats. J Bone Miner Metab 32(3):252–260CrossRefPubMed Yang N, Cui Y, Tan J, Fu X, Han X, Leng H, Song C (2014) Local injection of a single dose of simvastatin augments osteoporotic bone mass in ovariectomized rats. J Bone Miner Metab 32(3):252–260CrossRefPubMed
24.
go back to reference Lim SS, Kook SH, Bhattarai G, Cho ES, Seo YK, Lee JC (2015) Local delivery of COMP-angiopoietin 1 accelerates new bone formation in rat calvarial defects. J Biomed Mater Res Part A 103:2942–2951CrossRef Lim SS, Kook SH, Bhattarai G, Cho ES, Seo YK, Lee JC (2015) Local delivery of COMP-angiopoietin 1 accelerates new bone formation in rat calvarial defects. J Biomed Mater Res Part A 103:2942–2951CrossRef
25.
go back to reference Bone HG, Greenspan SL, Mckeever C, Bell N, Davidson M, Downs RW (2000) Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/Estrogen Study Group. J Clin Endocr Metab 85:720–726PubMed Bone HG, Greenspan SL, Mckeever C, Bell N, Davidson M, Downs RW (2000) Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/Estrogen Study Group. J Clin Endocr Metab 85:720–726PubMed
26.
go back to reference Xie QF, Xie JH, Dong TT, Su JY, Cai DK, Chen JP, Liu LF, Li YC, Lai XP, Tsim KW, Su ZR (2012) Effect of a derived herbal recipe from an ancient Chinese formula, Danggui Buxue Tang, on ovariectomized rats. J Ethnopharmacol 144(3):567–575CrossRef Xie QF, Xie JH, Dong TT, Su JY, Cai DK, Chen JP, Liu LF, Li YC, Lai XP, Tsim KW, Su ZR (2012) Effect of a derived herbal recipe from an ancient Chinese formula, Danggui Buxue Tang, on ovariectomized rats. J Ethnopharmacol 144(3):567–575CrossRef
27.
go back to reference Chen L, Yang L, Yao M, Cui XJ, Xue CC, Wang YJ, Shu B (2016) Biomechanical characteristics of osteoporotic fracture healing in ovariectomized rats: a systematic review. PLoS One 11:e0153120CrossRef Chen L, Yang L, Yao M, Cui XJ, Xue CC, Wang YJ, Shu B (2016) Biomechanical characteristics of osteoporotic fracture healing in ovariectomized rats: a systematic review. PLoS One 11:e0153120CrossRef
28.
go back to reference Vervloet MG, Brandenburg VM (2017) Circulating markers of bone turnover. J Nephrol 30:663–670CrossRef Vervloet MG, Brandenburg VM (2017) Circulating markers of bone turnover. J Nephrol 30:663–670CrossRef
29.
30.
go back to reference Tao ZS, Zhou WS, Tu KK, Huang ZL, Zhou Q, Sun T, Lv YX, Cui W, Yang L (2015) Treatment study of distal femur for parathyroid hormone (1–34) and beta-tricalcium phosphate on bone formation in critical-sized defects in osteopenic rats. J Cranio-Maxillo Fac Surg 43(10):2136–2143CrossRef Tao ZS, Zhou WS, Tu KK, Huang ZL, Zhou Q, Sun T, Lv YX, Cui W, Yang L (2015) Treatment study of distal femur for parathyroid hormone (1–34) and beta-tricalcium phosphate on bone formation in critical-sized defects in osteopenic rats. J Cranio-Maxillo Fac Surg 43(10):2136–2143CrossRef
31.
go back to reference Thanaviratananich S, Thanaviratananich S, Ngamjarus CJB (2011) The effect of BMP-2 on the osteoconductive properties of β-tricalcium phosphate in rat calvaria defects. Biomaterials 32:3855–3861CrossRef Thanaviratananich S, Thanaviratananich S, Ngamjarus CJB (2011) The effect of BMP-2 on the osteoconductive properties of β-tricalcium phosphate in rat calvaria defects. Biomaterials 32:3855–3861CrossRef
32.
go back to reference Rachner TD, Khosla S, Hofbauer LCJL (2011) Osteoporosis: now and the future. Lancet 377:1276–1287CrossRef Rachner TD, Khosla S, Hofbauer LCJL (2011) Osteoporosis: now and the future. Lancet 377:1276–1287CrossRef
33.
go back to reference Cao L, Liu G, Gan Y, Fan Q, Yang F, Zhang X, Tang T, Dai K (2012) The use of autologous enriched bone marrow MSCs to enhance osteoporotic bone defect repair in long-term estrogen deficient goats. Biomaterials 33(20):5076–5084CrossRef Cao L, Liu G, Gan Y, Fan Q, Yang F, Zhang X, Tang T, Dai K (2012) The use of autologous enriched bone marrow MSCs to enhance osteoporotic bone defect repair in long-term estrogen deficient goats. Biomaterials 33(20):5076–5084CrossRef
34.
go back to reference Williams J, Maitra S, Anderson M, Christiansen B, Reddi A, Lee MJ (2015) BMP-7 and bone regeneration: evaluation of dose–response in a rodent segmental defect model. J Orthop Trauma. 29:e336–e341CrossRef Williams J, Maitra S, Anderson M, Christiansen B, Reddi A, Lee MJ (2015) BMP-7 and bone regeneration: evaluation of dose–response in a rodent segmental defect model. J Orthop Trauma. 29:e336–e341CrossRef
35.
go back to reference Shi S, Gronthos S, Chen S, Reddi A, Counter CM, Robey PG, Wang CY (2002) Bone formation by human postnatal bone marrow stromal stem cells isenhanced by telomerase expression. Nat Biotechnol 20(6):587–591CrossRef Shi S, Gronthos S, Chen S, Reddi A, Counter CM, Robey PG, Wang CY (2002) Bone formation by human postnatal bone marrow stromal stem cells isenhanced by telomerase expression. Nat Biotechnol 20(6):587–591CrossRef
36.
go back to reference Hu Z, Zhang F, Yang Z, Zhang J, Zhang D, Yang N, Zhang Y, Cao K (2013) Low–dose aspirin promotes endothelial progenitor cell migration and adhesion and prevents senescence. Cell Biol Int 32:761–768CrossRef Hu Z, Zhang F, Yang Z, Zhang J, Zhang D, Yang N, Zhang Y, Cao K (2013) Low–dose aspirin promotes endothelial progenitor cell migration and adhesion and prevents senescence. Cell Biol Int 32:761–768CrossRef
37.
go back to reference Yamaza T, Miura Y, Bi Y, Liu Y, Akiyama K, Sonoyama W, Patel V, Gutkind S, Young M, Gronthos S, Le A, Wang CY, Chen W, Shi S (2008) Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents. PLoS One 3:907–911CrossRef Yamaza T, Miura Y, Bi Y, Liu Y, Akiyama K, Sonoyama W, Patel V, Gutkind S, Young M, Gronthos S, Le A, Wang CY, Chen W, Shi S (2008) Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents. PLoS One 3:907–911CrossRef
39.
go back to reference Xie H, Cui Z, Wang L, Xia Z, Hu Y, Xian L, Li C, Xie L, Crane J, Wan M, Zhen G, Bian Q, Yu B, Chang W, Qiu T, Pickarski M, Duong LT, Windle JJ, Luo X, Liao E, Cao X (2014) PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nat Med 20:1270–1278CrossRef Xie H, Cui Z, Wang L, Xia Z, Hu Y, Xian L, Li C, Xie L, Crane J, Wan M, Zhen G, Bian Q, Yu B, Chang W, Qiu T, Pickarski M, Duong LT, Windle JJ, Luo X, Liao E, Cao X (2014) PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nat Med 20:1270–1278CrossRef
40.
go back to reference Kusumbe AP, Ramasamy SK, Adams RH (2014) Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nat Biotechnol 507:323–328 Kusumbe AP, Ramasamy SK, Adams RH (2014) Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nat Biotechnol 507:323–328
Metadata
Title
Local administration of aspirin with β-tricalcium phosphate/poly-lactic-co-glycolic acid (β-TCP/PLGA) could enhance osteoporotic bone regeneration
Authors
Zhou-Shan Tao
Xing-Jing Wu
Wan-Shu Zhou
Xin-ju Wu
Wei Liao
Min Yang
Hong-Guang Xu
Lei Yang
Publication date
01-11-2019
Publisher
Springer Japan
Keyword
Bone Defect
Published in
Journal of Bone and Mineral Metabolism / Issue 6/2019
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI
https://doi.org/10.1007/s00774-019-01008-w

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