Osteoporos Int DOI 10.1007/s00198-014-2735-0
ORIGINAL ARTICLE
A comparative study of Sr-incorporated mesoporous bioactive glass scaffolds for regeneration of osteopenic bone defects L. Wei & J. Ke & I. Prasadam & R. J. Miron & S. Lin & Y. Xiao & J. Chang & C. Wu & Y. Zhang
Received: 12 September 2013 / Accepted: 22 April 2014 # International Osteoporosis Foundation and National Osteoporosis Foundation 2014
Abstract Summary Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis. While much investigation is focused on preventing disease progression, here we fabricate strontiumcontaining scaffolds and show that they enhance bone defect healing in the femurs of rats induced by ovariectomy. Introduction Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis due to its ability to prevent bone loss in osteoporotic patients. Although much emphasis has been placed on using pharmacological agents for the prevention of disease, much less attention has been placed on the construction of biomaterials following osteoporotic-related fracture. The aim of the present study was to incorporate bioactive strontium (Sr) trace element into mesoporous bioactive glass Lingfei Wei and Jin Ke contributed equally to this work. L. Wei : J. Ke : R. J. Miron : S. Lin : Y. Zhang (*) The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, People’s Republic of China e-mail: [email protected] J. Chang : C. Wu (*) State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People’s Republic of China e-mail: [email protected] I. Prasadam : Y. Xiao Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove Campus, Brisbane, Queensland 4059, Australia Y. Zhang Department of Oral Implantology, School of Stomatology, Wuhan University, Wuhan 430079, China
(MBG) scaffolds and to investigate their in vivo efficacy for bone defect healing in the femurs of rats induced by ovariectomy. Methods In total, 30 animals were divided into five groups as follows: (1) empty defect (control), (2) empty defects with estrogen replacement therapy, (3) defects filled with MBG scaffolds alone, (4) defects filled with MBG + estrogen replacement therapy, and (5) defects filled with strontiumincorporated mesopore-bioglass (Sr-MBG) scaffolds. Results The two groups demonstrating the highest levels of new bone formation were the defects treated with MBG + estrogen replacement therapy and the defects receiving SrMBG scaffolds as assessed by μ-CT and histological analysis. Furthermore, Sr scaffolds had a reduced number of tartrateresistant acid phosphatase-positive cells when compared to other modalities. Conclusion The results from the present study demonstrate that the local release of Sr from bone scaffolds may improve fracture repair. Future large animal models are necessary to investigate the future relationship of Sr incorporation into biomaterials. Keywords Bioactive scaffolds . Estrogen . Osteoporotic bone . Strontium
Introduction The success of biomaterial osteointegration depends not only on the properties of the implanted material but also on the harmonious integration and regenerative capability of the host bone. Concerns have therefore been raised about osteoporosis, a condition associated with a decrease in bone quality and quantity. People who often suffer from osteoporosis are more likely to suffer from bone fracture; therefore, emphasis should then be given to the investigation of better treatments for
Osteoporos Int
osteoporotic bone defects using effective and safe tissueengineering strategies [1–3]. Osteoporosis is often associated with a decrease in serum estrogen after menopause [4]. Many studies have established that estrogen can enhance osteoblast differentiation and increase bone formation [5, 6]; however, long-term systematic treatment with estrogen medication has a high probability of undesirable side effects [7, 8]. Therefore, new approaches have to be aimed to develop regeneration procedures that stimulate new bone formation while reversing bone loss with minimal/no side effects. In recent years, strontium ranelate, a newly developed drug, has been shown to be effective in reducing the risk of fractures in patients with osteoporosis [9–12]. Strontium (Sr) ions often act similarly to calcium in the human body, having strong bone-seeking properties [13–15]. In contrast to other available treatments for osteoporosis, Sr has been demonstrated to act by preventing bone loss and inhibiting osteoclast functions [15]. However, one drawback associated with the use of Sr is its bioavailability. Studies have shown that the bioavailability of orally administered strontium is only
ORIGINAL ARTICLE
A comparative study of Sr-incorporated mesoporous bioactive glass scaffolds for regeneration of osteopenic bone defects L. Wei & J. Ke & I. Prasadam & R. J. Miron & S. Lin & Y. Xiao & J. Chang & C. Wu & Y. Zhang
Received: 12 September 2013 / Accepted: 22 April 2014 # International Osteoporosis Foundation and National Osteoporosis Foundation 2014
Abstract Summary Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis. While much investigation is focused on preventing disease progression, here we fabricate strontiumcontaining scaffolds and show that they enhance bone defect healing in the femurs of rats induced by ovariectomy. Introduction Recently, the use of the pharmacological agent strontium ranelate has come to prominence for the treatment of osteoporosis due to its ability to prevent bone loss in osteoporotic patients. Although much emphasis has been placed on using pharmacological agents for the prevention of disease, much less attention has been placed on the construction of biomaterials following osteoporotic-related fracture. The aim of the present study was to incorporate bioactive strontium (Sr) trace element into mesoporous bioactive glass Lingfei Wei and Jin Ke contributed equally to this work. L. Wei : J. Ke : R. J. Miron : S. Lin : Y. Zhang (*) The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, People’s Republic of China e-mail: [email protected] J. Chang : C. Wu (*) State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People’s Republic of China e-mail: [email protected] I. Prasadam : Y. Xiao Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove Campus, Brisbane, Queensland 4059, Australia Y. Zhang Department of Oral Implantology, School of Stomatology, Wuhan University, Wuhan 430079, China
(MBG) scaffolds and to investigate their in vivo efficacy for bone defect healing in the femurs of rats induced by ovariectomy. Methods In total, 30 animals were divided into five groups as follows: (1) empty defect (control), (2) empty defects with estrogen replacement therapy, (3) defects filled with MBG scaffolds alone, (4) defects filled with MBG + estrogen replacement therapy, and (5) defects filled with strontiumincorporated mesopore-bioglass (Sr-MBG) scaffolds. Results The two groups demonstrating the highest levels of new bone formation were the defects treated with MBG + estrogen replacement therapy and the defects receiving SrMBG scaffolds as assessed by μ-CT and histological analysis. Furthermore, Sr scaffolds had a reduced number of tartrateresistant acid phosphatase-positive cells when compared to other modalities. Conclusion The results from the present study demonstrate that the local release of Sr from bone scaffolds may improve fracture repair. Future large animal models are necessary to investigate the future relationship of Sr incorporation into biomaterials. Keywords Bioactive scaffolds . Estrogen . Osteoporotic bone . Strontium
Introduction The success of biomaterial osteointegration depends not only on the properties of the implanted material but also on the harmonious integration and regenerative capability of the host bone. Concerns have therefore been raised about osteoporosis, a condition associated with a decrease in bone quality and quantity. People who often suffer from osteoporosis are more likely to suffer from bone fracture; therefore, emphasis should then be given to the investigation of better treatments for
Osteoporos Int
osteoporotic bone defects using effective and safe tissueengineering strategies [1–3]. Osteoporosis is often associated with a decrease in serum estrogen after menopause [4]. Many studies have established that estrogen can enhance osteoblast differentiation and increase bone formation [5, 6]; however, long-term systematic treatment with estrogen medication has a high probability of undesirable side effects [7, 8]. Therefore, new approaches have to be aimed to develop regeneration procedures that stimulate new bone formation while reversing bone loss with minimal/no side effects. In recent years, strontium ranelate, a newly developed drug, has been shown to be effective in reducing the risk of fractures in patients with osteoporosis [9–12]. Strontium (Sr) ions often act similarly to calcium in the human body, having strong bone-seeking properties [13–15]. In contrast to other available treatments for osteoporosis, Sr has been demonstrated to act by preventing bone loss and inhibiting osteoclast functions [15]. However, one drawback associated with the use of Sr is its bioavailability. Studies have shown that the bioavailability of orally administered strontium is only
