Multifunctional Nanoengineered Hydrogels Consisting of Black Phosphorus Nanosheets Upregulate Bone Formation

Abstract

Tissue‐engineered hydrogels have received extensive attention as their mechanical properties, chemical compositions, and biological signals can be dynamically modified for mimicking extracellular matrices (ECM). Herein, the synthesis of novel double network (DN) hydrogels with tunable mechanical properties using combinatorial screening methods is reported. Furthermore, nanoengineered (NE) hydrogels are constructed by addition of ultrathin 2D black phosphorus (BP) nanosheets to the DN hydrogels with multiple functions for mimicking the ECM microenvironment to induce tissue regeneration. Notably, it is found that the BP nanosheets exhibit intrinsic properties for induced CaP crystal particle formation and therefore improve the mineralization ability of NE hydrogels. Finally, in vitro and in vivo data demonstrate that the BP nanosheets, mineralized CaP crystal nanoparticles, and excellent mechanical properties provide a favorable ECM microenvironment to mediate greater osteogenic cell differentiation and bone regeneration. Consequently, the combination of bioactive chemical materials and excellent mechanical stimuli of NE hydrogels inspire novel engineering strategies for bone‐tissue regeneration.

<p>Advanced Black Phosphorus Nanomaterials for Bone Regeneration</p>

“…Similar to BP nanosheets, BPQDs (5.4 nm) with rapid renal clearance showed excellent PDT effects under light irradiation and could effectively generate ROS to kill cancer cells. 63 Based on the above analysis, the excellent PTT and PDT abilities of BP nanomaterials make it a promising The advantages of BP nanomaterials for bone regeneration, including biocompatibility, 101 biodegradability, 25 drug loading, 71 and photothermal 26 and photodynamic effects. 55,68 Reproduced with permission from Liu X, Miller AL, II, Park S, et al application for promoting bone regeneration, especially in disease conditions such as cancer and infection.…”

“…98,99 Wang et al introduced ultrathin BP nanosheets into double network hydrogels to induce tissue regeneration. 25 From the electron microscopy and X-ray diffraction results, the incorporated BP nanosheets in the hydrogel exhibit intrinsic properties for induced CaP crystal particle formation after soaked in simulated body fluid solution ( Figure 4A). Thus, this platform provides a favorable ECM microenvironment to promote greater osteogenic cell differentiation and bone regeneration.…”

“…It Figure 4 (A) The introduction of BP nanosheets to double network hydrogels could facilitate inorganic matrix formation: SEM (A1, A2) and (A3) XRD results. 25 (B) Photothermal stimulation of bone regeneration: (B1) illustration the progress of rat tibia implantation and subsequent NIR irradiation; (B2) infrared thermo-graphic maps in irradiated areas; (B3) BV/TV ratio results, ** denotes p < 0.01 compared with the PLGA group. 24 (C) Apt-bioinspired MVs can stimulate bone regeneration: (C1) overview of Apt-bioinspired MVs in cell mineralization; (C2) micro-CT reconstruction of the bone defect.…”

“…Copyright 2019, Wiley-VCH. 25 Reproduced with permission from Tong LP, Liao Q, Zhao YT et al Near-infrared light control of bone regeneration with biodegradable photothermal osteoimplant. Biomaterials.…”

“…24 Wang et al demonstrated that BP incorporated hydrogels can induce mineralization and enhance osteogenic cell differentiation and bone regeneration. 25 Other studies showed that BP-based materials in bone defects can produce local mild heat and accelerate bone regeneration. 24,26 BP nanomaterials also exhibit excellent PTT and PDT effects, which can be used to enhance bone regeneration, even under disease conditions such as tumors and infections.…”