One-step electrodeposition synthesis of bisphosphonate loaded magnesium implant: A strategy to modulate drug release for osteoporotic fracture healing

doi:10.1016/j.jmst.2020.10.055

Abstract

Abstract:

Osteoporotic fracture with increase of aging population became an urgent orthopedic problem. Bisphosphonates were widely recommended as effective clinical treatment drugs. Combination of biodegradable Mg-based implants and merits of bisphosphonates was suggested for osteoporotic fracture healing. Considering the mild and sustained drug release, a novel one-step electrodeposition synthesis of drug loaded coating was proposed in this study. In comparison to conventional soaking method, encapsulated zoledronate coating by one-step electrodeposition method could modulate drug release in first diffusion-controlled and later degradation-controlled manner. The in vitro cell response to zoledronate loaded coating showed enhanced proliferation and osteogenic differentiation of osteoblasts and no significant inhibition on osteoclasts, which could improve bone-forming and decrease bone resorption due to osteoporosis.

Key words: Bisphosphonate, Magnesium, Coating, Electrodeposition, Osteoporosis

Peng Wan, Weidan Wang, Lizhen Zheng, Ling Qin, Ke Yang. One-step electrodeposition synthesis of bisphosphonate loaded magnesium implant: A strategy to modulate drug release for osteoporotic fracture healing[J]. J. Mater. Sci. Technol., 2021, 78: 92-99.

Figures/Tables 9

Fig. 1. Surface and cross-sectional morphologies of different coatings at low and high magnification, (a) PED coating, (b) zoledronate loaded coating by immersion method, (c) zoledronate loaded coating by one-step PED synthesis.

Fig. 2. The composition analysis corresponding to the site shown in Fig. 1 (a2, b2, c2) by EDS point scan.

Fig. 3. Cross-sectional composition analysis corresponding to the zone shown in Fig. 1(c3) by EDS line scan and mapping.

Fig. 4. (a) XRD patterns and (b) FTIR-ATR spectra of PED coatings without and with zoledronate loading, pure zoledronate powder was set as the reference.

Fig. 5. (a) pH variation, (b) Mg ions release and (c) zoledronate release profile after immersion of 7 days.

Fig. 6. Cell response by incubation with the extracts of different coatings and pure Mg, (a) O.D. value of MC3T3-E1 proliferation, (b) ALP activity of MC3T3-E1, (c) O.D. value of RAW264.7 proliferation and (d) cell morphologies of RAW264.7 after incubation of 3 days, * p < 0.05, *** p < 0.01.

Fig. 7. Calcium Nodules staining of (a) Mg, (b) Zol-PED and (c) Zol-IM groups, (d) blank control.

Fig. 8. Schematic of the Zoledronate loaded coating preparation by one-step electrodeposition and soaking methods.

Table 1 Different methods for synthesis of zoledronate (ZA) loaded coating on magnesium and corresponding release amount of ZA.

Fabrication method	Cumulative release amount of ZA (μg/mL)					Reference
Fabrication method	1-day	3-day	4-day	7-day	25-day	Reference
ZA was dissolved in the PLA/ethyl acetate solution + Ca-P coating	∼1	∼1.3	∼1.33	∼1.6	∼2	[15]
Ca-P coating was soaked in the ZA solution	∼1	∼2.3	∼2.49	∼2.49	N/A	[13,14]
HF pre-treatment + Dip coating	∼27	N/A	∼31	∼40	N/A	[16]
One-step PED method	0.96	1.5	N/A	2.11	N/A	This study
Ca-P coating was soaked in the ZA solution	1.4	2.48	N/A	2.685	N/A	This study

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