Vitamin D3-loaded calcium citrate/calcium sulfate composite cement with enhanced physicochemical properties, drug release, and cytocompatibility

Abstract

Vitamin D3 (VD3), an important regulator of calcium and phosphate ion concentrations in blood serum, participates in bone formation by promoting calcium and citrate deposition at defect sites while further stimulating bone calcification and osteoblast function. In this study, VD3-loaded calcium sulfate (VD3/CS) and calcium citrate/calcium sulfate (VD3/ CC/CS) cements were successfully fabricated for the first time. The incorporation of VD3 into the cements did not alter their structures or physicochemical properties. Additionally, compared with the VD3/CS cement, the VD3/CC/CS composite cement showed higher mechanical strength (28.87 MPa), better injectability (94.48%), and more appropriate setting time (23.7 min). Depending on the method by which the loaded VD3 was adsorbed, both VD3/CS and VD3/CC/ CS cements could achieve sustained drug release. However, due to their different compositions, VD3/CS cement samples, owing to the dissolution of their matrix, showed faster VD3 release rates, while VD3/CC/CS composite cement samples showed more controlled VD3 release rates, owing to the presence of a physical barrier created by calcium citrate. The VD3/CC/CS composite cement samples also demonstrated excellent bioactivity at cellular level, indicating that the VD3/CC/CS composite cement might be beneficial for the localised treatment of bone defects, especially osteoporotic bone.

Vitamin D3 Stimulates Proliferation Capacity, Expression of Pluripotency Markers, and Osteogenesis of Human Bone Marrow Mesenchymal Stromal/Stem Cells, Partly through SIRT1 Signaling

“…The biological potential of cholecalciferol (VD3) within regenerative medicine has not been sufficiently investigated. Recent studies have implied its significance in tissue engineering, showing that its incorporation in various biomaterial matrices or 3D scaffolds may improve MSCs’ regenerative potential [ 7 , 8 , 9 ]. In addition, preconditioning/priming procedures represent some of the key strategies to improve MSCs’ function and enable more direct translation to clinical practice.…”

“…Considered to be a cornerstone of bone tissue engineering, the application of BM-MSCs has been combined with various types of biomaterials to facilitate the ossification process and improve clinical therapy of delayed bone healing—usually related to various bone diseases, injuries, or tumor surgery [ 5 ]. Some of the recent advances that have emerged with an aim to develop more effective therapies for enhanced bone regeneration propose loading of different hybrid biomaterial matrices or 3D scaffolds with vitamin D3 [ 6 , 7 , 8 , 9 ].…”

“…In addition, recent investigations utilizing various hybrid biomaterial scaffolds or composites loaded with VD3 have demonstrated their enhanced biocompatibility and/or osteoinductive effects on MSCs, implying the advantages of their use for the treatment of bone defects. Specifically, a stimulatory effect on murine BM-MSCs’ viability and proliferation rate was demonstrated for a VD3-loaded composite cement scaffold containing calcium sulfate and calcium citrate, which enabled sustained and controllable release of this vitamin [ 7 ]. In addition, polycaprolactone/gelatin scaffolds loaded with VD3 in combination with nano-hydroxyapatite (HAP) stimulated osteogenesis of adipose tissue MSCs, increasing the ALP activity in the early stages and mineralization in the late stages of differentiation [ 6 ].…”

Developing a novel magnesium calcium phosphate/sodium alginate composite cement with high strength and proper self-setting time for bone repair

“…8 In recent years, magnesium phosphate cements (MPC) have shown much attractive in clinical researches because of their high compressive strength and biocompatibility. 9,10 The MPC compounds are usually composed of magnesium oxide (MgO) and phosphate acidic salts, such as NH 4 11 Due to the rapid hydration and exothermic acid-base reaction, an amorphous gel is formed with fast setting when the MPC powders mixing with water. This gel crystallizes around unreacted MgO particles and forms a core-shell scheme with the formation of durable material.…”

“…1 Although many kinds of cements, such as poly-methyl methacrylate (PMMA), calcium phosphate cement (CPC) and calcium sulfate (CS) have been used in different orthopedic applications for several decades, there are still many deficiencies in single bone cement materials. 2–4 For instance, PMMA cement has the shortcomings of highly exothermic polymerization, non-degradability and bio-inertness, CPC cement has the disadvantages of low biodegradation rate and poor mechanical properties, and CS cement has the fast degradation rate that does not match the rate of bone growth. 5–7 Therefore, it is necessary to develop composite cements which combine the advantages and overcome the disadvantages of different components.…”