A Facile Crystallization Strategy to Turn Calcium Bisphosphonates into Novel Osteogenesis‐Inducing Biomaterials

Abstract

Insoluble metal bisphosphonates (BPs) are considered an ideal alternative to the soluble counterparts in regenerative medicine due to their increased BP release profile, but still present undesired properties (e.g., low stability, uncontrolled degradation, and poor biocompatibility). Through a simple crystallization on a solid calcium hydroxyapatite (HA)‐based substrate from a BP precursor solution in 30 days, a series of insoluble calcium BP (CaBP) crystals are developed. These crystals, including calcium alendronate (CaAln), calcium pamidronate (CaPam), calcium incadronate (CaInc), calcium risedronate (CaRis), calcium zoledronate (CaZol), and calcium di‐minodronate (Ca(Min)2), present high purity, regular morphologies and excellent biodegradability. It is demonstrated that these CaBPs can induce osteogenic differentiation of adipose‐derived mesenchymal stem cells in vitro in the absence of other osteogenic inducers. It is further found that CaBP induces bone formation more effectively in a femur defect rabbit model in three months but with a lower in vivo hematotoxicity than the clinically used HA during osteogenesis. It is believed that these desired biological properties arise from the capability of the insoluble CaBPs in releasing BPs in a sustained manner for stimulating osteogenesis. This work provides a significant strategy for turning CaBPs into novel biomaterials for tissue regeneration and demonstrates their great potential in the clinic.

3D Printed Calcium Phosphate Physiochemically Dual-Regulating Pro-Osteogenesis and Antiosteolysis for Enhancing Bone Tissue Regeneration

“…Zoledronate, one in the bisphosphonate’s family, is broadly classified as an antiresorptive medication and operates through a multifaceted mechanism to effectively inhibit bone resorption. , Upon administration, zoledronate is preferentially taken up by bone tissue due to its strong affinity for hydroxyapatite . Zoledronate disrupts osteoclast function by inhibiting the mevalonate pathway through its impact on the enzyme farnesyl pyrophosphate synthase .…”

“…20,21 Upon administration, zoledronate is preferentially taken up by bone tissue due to its strong affinity for hydroxyapatite. 22 Zoledronate disrupts osteoclast function by inhibiting the mevalonate pathway through its impact on the enzyme farnesyl pyrophosphate synthase. 23 This pathway is essential for the synthesis of molecules necessary for osteoclast activity.…”