In vitro Chondrocyte Responses in Mg-doped Wollastonite/Hydrogel Composite Scaffolds for Osteochondral Interface Regeneration

Abstract

The zone of calcified cartilage (ZCC) is the mineralized region between the hyaline cartilage and subchondral bone and is critical in cartilage repair. A new non-stoichiometric calcium silicate (10% Ca substituted by Mg; CSi-Mg10) has been demonstrated to be highly bioactive in an osteogenic environment in vivo. This study is aimed to systematically evaluate the potential to regenerate osteochondral interface with different amount of Ca-Mg silicate in hydrogel-based scaffolds, and to compare with the scaffolds containing conventional Ca-phosphate biomaterials. Hydrogel-based porous scaffolds combined with 0–6% CSi-Mg10, 6% β-tricalcium phosphate (β-TCP) or 6% nanohydroxyapatite (nHAp) were made with three-dimensional (3D) printing. An increase in CSi-Mg10 content is desirable for promoting the hypertrophy and mineralization of chondrocytes, as well as cell proliferation and matrix deposition. Osteogenic and chondrogenic induction were both up-regulated in a dose-dependent manner. In comparison with the scaffolds containing 6% β-TCP or nHAp, human deep zone chondrocytes (hDZCs) seeded on CSi-Mg10 scaffold of equivalent concentration exhibited higher mineralization. It is noteworthy that the hDZCs in the 6% CSi-Mg10 scaffolds maintained a higher expression of the calcified cartilage zone specific extracellular matrix marker and hypertrophic marker, collagen type X. Immunohistochemical and Alizarin Red staining reconfirmed these findings. The study demonstrated that hydrogel-based hybrid scaffolds containing 6% CSi-Mg10 are particularly desirable for inducing the formation of calcified cartilage.

Wollastonite/TCP composites for bone regeneration: systematic review and meta-analysis

“…Bioactive biomaterials containing silicon (Si) are capable of inducing the nucleation, precipitation, and formation of a layer of amorphous CaP (apatite) on the surface of these materials and, thus, amplify the mechanism of bone neoformation in vivo [1, 17-20, 22, 29]. In addition to this factor, the higher NB percentage of composites containing W>TCP content ratio can be attributed to the fact that, when compared to other bone substitutes, W presents greater bioactivity by the effect of the release of calcium (Ca 2+ ) and silicate (SiO 3 2-) ions, substantial during the osteogenesis mechanism [1,5,6,17,18]. Moreover, the presence of SiO 3 2also induces proliferation, differentiation, and increased activity of osteoblasts and, consequently, promotes biomineralization, elementary events during bone repair [2,16,19,20,31,50].…”

“…) during osteogenesis [6,17,18]. In addition to W, bioceramics based on calcium phosphate (CaP), especially hydroxyapatite (HA) and tricalcium phosphate (TCP), have been widely used for decades for the synthesis and processing of bone substitute biomaterials [19][20][21].…”

“…In these conditions, the tissue repair is not consolidated by regeneration, due to the lack of adequate blood supply and a three-dimensional (3D) scaffold that enable cellular events [2][3][4], resulting in fibrosis. Therefore, it becomes essential to use biomaterials or regenerative techniques to restore, in the shortest possible time, the lost structure and functions, considering that these situations, in addition to causing morbidity, generate high costs for the public health sector, since they require multiple long-term surgical repair procedures [5,6] and, consequently, burden the public health and social security system. In these conditions, given the excellent osteogenic potential of the autogenous graft, this would be the first choice.…”

“…Among the bioceramic substrates most used for the synthesis of composites, wollastonite (W) has recently stood out due to its biocompatibility, osteoconductivity, biodegradability, solubility, and, especially, bioactivity [6][7][8]. This calcium metasilicate is acicular, non-metallic, and can be of natural or synthetic origin.…”

“…When obtained synthetically, it presents stable physical-chemical characteristics, which allows 3 types found in nature: triclinic form, most common and predominant one; monoclinic parawollastonite (b-CaSiO 3 ), obtained at low temperatures; and triclinic pseudowollastonite (p-W), acquired at high temperatures above 1200 ºC [11,13,14], although p-W is a polymorphic silicate stable at temperatures higher than 1030 ºC [15]. For biomedical purposes, wollastonite (W) has been synthesized, processed and used in different formats and geometric shapes, such as metal alloy coatings, microspheres, granules, and sintered or non-sintered porous 3D scaffolds [6,16] due to its bioactivity, resulting from the substantial release of calcium (Ca 2+ ) and silicate (SiO 3…”