Self-Assembled Injectable Nanocomposite Hydrogels Coordinated by in Situ Generated CaP Nanoparticles for Bone Regeneration

Abstract

Due to the great similarity to the natural extracellular matrix and minimally invasive surgeries, injectable hydrogels are appealing biomaterials in cartilage and bone tissue engineering. Nevertheless, undesirable mechanical properties and bioactivity greatly hamper their availability in clinic applications. Here, we developed an injectable nanocomposite hydrogel by in situ growth of CaP nanoparticles (ICPNs) during the free-radical polymerization of dimethylaminoethyl methacrylate (DMAEMA) and 2-hydroxyethyl methacrylate (HEMA) matrix (PDH) for bone regeneration. The ICPNs are self-assembled by incorporation of poly-l-glutamic acid (PGA) with abundant carboxyl functional groups during the formation of carboxyl–Ca2+ coordination and further CaP precipitation. Furthermore, the carboxyl groups of PGA could interact with the tertiary amines of DMAEMA fragments and thus improve the mechanical strength of hydrogels. Upon mixing solutions of DMAEMA and HEMA bearing PGA, Ca2+, and PO4 3–, this effective and dynamic coordination led to the rapid self-assembly of CaP NPs and PDH nanocomposite hydrogels (PDH/mICPN). The obtained optimal nanocomposite hydrogels exhibited suitable injectable time, an enhanced tensile strength of 321.1 kPa, and a fracture energy of 29.0 kJ/m2 and dramatically facilitated cell adhesion and upregulated osteodifferentiation compared to hydrogels prepared by blending ex situ prefabricated CaP NPs. In vivo experiments confirmed the promoted osteogenesis, which shows a striking contrast to pure PDH hydrogels. Additionally, the methacrylate groups on the monomers could easily be functionalized with aptamers and thereby facilitate recognition and capturing of bone marrow stromal cells both in vitro and in vivo and strengthen the bone regeneration. We believe that our conducted research about in situ self-assembled CaP nanoparticle-coordinated hydrogels will open a new avenue for bone regeneration in the future endeavors.

Exosomes: A Novel Therapeutic Agent for Cartilage and Bone Tissue Regeneration

“…Although great progress has been made in bone tissue engineering, such as engineering scaffolds, hydrogels, growth factors, and cell-based therapies, undesirable efficacy and safety issues remain unaddressed. [35][36][37] Moreover, current research on bone regeneration often focuses on the specific osteogenic stage and affiliated cell behaviors, impeding clear understanding of bone biogenesis and novel approaches to stimulate bone regeneration. 25 Exosomes provide not merely a new version to disentangle the complicated bone healing processes but a novel strategy to improve bone repair.…”

Fabrication of Injectable, Porous Hyaluronic Acid Hydrogel Based on an In-Situ Bubble-Forming Hydrogel Entrapment Process

“…In recent years, injectable biomaterials, which can be applied via minimally invasive methods in the clinic and can be formed into any desired shape to match irregular defects, have gathered much attention in the field of tissue regeneration [1][2][3][4]. In particular, injectable hydrogels, free-flowing fluids before injection that go through a spontaneous transformation into semisolid hydrogels once a reaction is initiated, have emerged as a promising platform for clinical applications.…”

Modified Nanoparticles as Potential Agents in Bone Diseases: Cancer and Implant-Related Complications

“…Those results corresponded with in vitro assessment, where NPs were non-toxic and promoted osteoblast formations from BMSCs through activation of the TGF-ß1/BMP/Smads/Runx2 pathway [76]. Study designed by Kuang et al is especially interesting because they created an injectable material containing nanocomposite hydrogel and CaPNPs [77]. The injectable material was potentially convenient to use and its effectiveness in promoting osteogenesis was proven both in vitro and in vivo [77].…”

“…Study designed by Kuang et al is especially interesting because they created an injectable material containing nanocomposite hydrogel and CaPNPs [77]. The injectable material was potentially convenient to use and its effectiveness in promoting osteogenesis was proven both in vitro and in vivo [77].…”