Two-Dimensional Magnesium Phosphate Nanosheets Form Highly Thixotropic Gels That Up-Regulate Bone Formation

Abstract

Hydrogels composed of two-dimensional (2D) nanomaterials have become an important alternative to replace traditional inorganic scaffolds for tissue engineering. Here, we describe a novel nanocrystalline material with 2D morphology that was synthesized by tuning the crystallization of the sodium-magnesium-phosphate system. We discovered that the sodium ion can regulate the precipitation of magnesium phosphate by interacting with the crystal's surface causing a preferential crystal growth that results in 2D morphology. The 2D nanomaterial gave rise to a physical hydrogel that presented extreme thixotropy, injectability, biocompatibility, bioresorption, and long-term stability. The nanocrystalline material was characterized in vitro and in vivo and we discovered that it presented unique biological properties. Magnesium phosphate nanosheets accelerated bone healing and osseointegration by enhancing collagen formation, osteoblasts differentiation, and osteoclasts proliferation through up-regulation of COL1A1, RunX2, ALP, OCN, and OPN. In summary, the 2D magnesium phosphate nanosheets could bring a paradigm shift in the field of minimally invasive orthopedic and craniofacial interventions because it is the only material available that can be injected through high gauge needles into bone defects in order to accelerate bone healing and osseointegration.

Multifunctional Nanoengineered Hydrogels Consisting of Black Phosphorus Nanosheets Upregulate Bone Formation

“…These results suggested that nanoengineered (NE) hydrogel‐based 2D nanomaterials acting as bioactive substitutes may have great potential for load‐bearing tissue applications. However, such 2D nanomaterials are characterized by insufficient degradation and bioresorption in vivo, which may be a concern for tissue engineering and biomedical applications …”

Phosphorus Science-Oriented Design and Synthesis of Multifunctional Nanomaterials for Biomedical Applications

“…The combination of phosphate ions and metal elements creates abundant metal phosphate materials. The development of nanotechnology has spawned a series of metal phosphate nanomaterials, mainly calcium phosphate nanomaterials (CaPs), [89][90][91] hydroxyapatite nanomaterials, 92,93 manganese phosphate nanomaterials (MnPs), 94,95 magnesium phosphate nanomaterials (MgPs), 96,97 and zirconium phosphate nanomaterials (ZrPs). 98,99 These metal phosphate nanomaterials also present excellent biocompatibility and biodegradability.…”

Applications of Nanosheets in Frontier Cellular Research

“…In addition, some novel types of nanosheets are developed specifically for cell culture and tissue engineering. Laurenti et al developed a magnesium phosphate nanosheet-based thixotropic gel, and osteoblast cells could adhere onto the 2D structures and form colonies [ 33 ]. Functionalized nanosheets were also synthesized onto traditional medical materials for improving cell culture.…”