Study of Sr–Ca–Si-based scaffolds for bone regeneration in osteoporotic models

Abstract

Bone tissue engineering has emerged as a promising alternative therapy for patients who suffer bone fractures or defects caused by trauma, congenital diseases or tumours. However, the reconstruction of bone defects combined with osteoporosis remains a great challenge for clinicians and researchers. Based on our previous study, Ca–Si-based bioceramics (MSCs) showed enhanced bone formation capabilities under normal conditions, and strontium was demonstrated to be therapeutic in promoting bone quality in osteoporosis patients. Therefore, in the present study, we attempted to enlarge the application range of MSCs with Sr incorporation in an osteoporotic bone regeneration model to evaluate whether Sr could assist in regeneration outcomes. In vitro readout suggested that Sr-incorporated MSC scaffolds could enhance the expression level of osteogenic and angiogenic markers of osteoporotic bone mesenchymal stem cells (OVX BMSCs). Animal experiments showed a larger new bone area; in particular, there was a tendency for blood vessel formation to be enhanced in the Sr-MSC scaffold group, showing its positive osteogenic capacity in bone regeneration. This study systematically illustrated the effective delivery of a low-cost therapeutic Sr agent in an osteoporotic model and provided new insight into the treatment of bone defects in osteoporosis patients.

References

[1] Fathi Kazerooni A, Pozo JM, McCloskey EV, Saligheh Rad H, Frangi AF. Diffusion MRI for assessment of bone quality; a review of findings in healthy aging and osteoporosis. J. Magn. Reson Imaging, 2020, 51: 975-992.

[2] Gallagher JC. Advances in osteoporosis from 1970 to 2018. Menopause, 2018, 25: 1403-1417.

[3] Amin B, . Dielectric properties of bones for the monitoring of osteoporosis. Med. Biol. Eng. Comput., 2019, 57: 1-13.

[4] Chen LR, Ko NY, Chen KH. Medical treatment for osteoporosis: from molecular to clinical opinions. Int. J. Mol. Sci., 2019, 20: 2213.

[5] Jakob F, . Bone tissue engineering in osteoporosis. Maturitas, 2013, 75: 118-124.

[6] Chandran S, John A. Osseointegration of osteoporotic bone implants: role of stem cells, Silica and Strontium—a concise review. J. Clin. Orthop. Trauma, 2019, 10: S32-S36.

[7] Fernandez JM, . Strontium ranelate prevents the deleterious action of advanced glycation endproducts on osteoblastic cells via calcium channel activation. Eur. J. Pharmacol., 2013, 706: 41-47.

[8] Lin SH, Zhang WJ, Jiang XQ. Applications of bioactive ions in bone regeneration. Chin. J. Dent. Res., 2019, 22: 93-104.

[9] Kargozar S, Montazerian M, Fiume E, Baino F. Multiple and promising applications of Strontium (Sr)-containing bioactive glasses in bone tissue engineering. Front. Bioeng. Biotechnol., 2019, 7: 161.

[10] Lu Y, . Recent advances in cell sheet technology for bone and cartilage regeneration: from preparation to application. Int. J. Oral. Sci., 2019, 11: 17.

[11] Gianni-Barrera R, . Therapeutic vascularization in regenerative medicine. Stem Cells Transl. Med., 2020, 9: 433-444.

[12] Shadjou N, Hasanzadeh M. Bone tissue engineering using silica-based mesoporous nanobiomaterials:Recent progress. Mater. Sci. Eng. C. Mater. Biol. Appl., 2015, 55: 401-409.

[13] Zeng D, . Fabrication of large-pore mesoporous Ca-Si-based bioceramics for bone regeneration. Int. J. Nanomed., 2017, 12: 8277-8287.

[14] Babrawala I, Munivenkatappa Lakshmaiah Venkatesh P, Bangalore Varadhan K. A novel approach using 15% natural chitosan gel in the management of intrabony defects: a pilot study. Chin. J. Dent. Res., 2016, 19: 231-237.

[15] Bose S, Sarkar N. Natural medicinal compounds in bone tissue engineering. Trends Biotechnol., 2020, 38: 404-417.

[16] Zhu L, Luo D, Liu Y. Effect of the nano/microscale structure of biomaterial scaffolds on bone regeneration. Int. J. Oral. Sci., 2020, 12: 6.

[17] Jimenez M, Abradelo C, San Roman J, Rojo L. Bibliographic review on the state of the art of strontium and zinc based regenerative therapies. Recent developments and clinical applications. J. Mater. Chem. B, 2019, 7: 1974-1985.

[18] Wen J, . Strontium delivery on topographical titanium to enhance bioactivity and osseointegration in osteoporotic rats. J. Mater. Chem. B, 2015, 3: 4790-4804.

[19] Prabha RD, . Strontium ion reinforced bioceramic scaffold for load bearing bone regeneration. Mater. Sci. Eng. C. Mater. Biol. Appl., 2020, 109: 110427.

[20] Sabio RM, Meneguin AB, Ribeiro TC, Silva RR, Chorilli M. New insights towards mesoporous silica nanoparticles as a technological platform for chemotherapeutic drugs delivery. Int. J. Pharm., 2019, 564: 379-409.

[21] Liu Y, Liu S, Fu Y, Chang DT, Zhou YH. Mineralised collagen scaffolds loaded with stromal cell-derived factor-1 improve mandibular bone regeneration. Chin. J. Dent. Res., 2014, 17: 23-29.

[22] Zhao S, . Three-dimensional printed strontium-containing mesoporous bioactive glass scaffolds for repairing rat critical-sized calvarial defects. Acta Biomater., 2015, 12: 270-280.

[23] Wu C, Zhou Y, Lin C, Chang J, Xiao Y. Strontium-containing mesoporous bioactive glass scaffolds with improved osteogenic/cementogenic differentiation of periodontal ligament cells for periodontal tissue engineering. Acta Biomater., 2012, 8: 3805-3815.

[24] Li Y, . Effects of strontium on proliferation and differentiation of rat bone marrow mesenchymal stem cells. Biochem. Biophys. Res. Commun., 2012, 418: 725-730.

[25] Lin K, . Strontium substituted hydroxyapatite porous microspheres: surfactant-free hydrothermal synthesis, enhanced biological response and sustained drug release. Chem. Eng. J., 2013, 222: 49-59.

[26] Zhang W, . VEGF and BMP-2 promote bone regeneration by facilitating bone marrow stem cell homing and differentiation. Eur. Cell Mater., 2014, 27: 1-11.

[27] Wu Q, . Antibacterial property, angiogenic and osteogenic activity of Cu-incorporated TiO2 coating. J. Mater. Chem. B, 2014, 2: 6738-6748.

[28] Anand A, . Preparation and in vivo biocompatibility studies of different mesoporous bioactive glasses. J. Mech. Behav. Biomed. Mater., 2019, 89: 89-98.

[29] Wang X, . Alendronate delivery on amino modified mesoporous bioactive glass scaffolds to enhance bone regeneration in osteoporosis rats. Artif. Cells Nanomed. Biotechnol., 2018, 46: 171-181.

[30] Wen J, . In vitro and in vivo evaluation of silicate-coated polyetheretherketone fabricated by electron beam evaporation. ACS Appl. Mater. Interfaces, 2016, 8: 13197-13206.

Funding

National Natural Science Foundation of China (National Science Foundation of China)(81921002, 81900970)