Feasibility of ceramic-polymer composite cryogels as scaffolds for bone tissue engineering

Abstract

The purpose of the current study was to investigate whether the cryopolymerization technique is capable of producing suitable scaffolds for bone tissue engineering. Cryopolymers made of 2-hydroxyethyl methacrylate and acrylic acid with (W1 and W20) and without (W0) wollastonite particles were prepared. The elastic modulus of the specimens rose one order of magnitude from W1 to W20. Total porosity reached 56% for W0, 72% for W1 and 36% for W20, with pore sizes of up to 2 mm, large interconnection sizes of up to 1 mm and small interconnection sizes of 50-80 µm on dry specimens. Cryogels swell up to 224 ± 17% for W0, 315 ± 18% for W1 and 231 ± 27% for W20 specimens, while maintaining the integrity of the bodies. Pore sizes > 5 mm can be observed for swollen specimens. The biocompatibility of the samples was tested using human mesenchymal stem cells isolated from bone marrow and adipose tissues. Both types of cells attached and grew on the three tested substrates, colonized their inner regions and organized an extracellular cell matrix. Fibronectin and osteopontin levels decreased in the media from cells cultured on W20 samples, likely due to increased binding on the ECM deposited by cells. The osteoprotegerin-to-receptor activator of nuclear factor-κB ligand secretion ratios increased with increasing wollastonite content. Altogether, these results indicate that an appropriate balance of surface properties and structure that favours stromal cell colonization in the porous cryogels can be achieved by modulating the amount of wollastonite.

Focal adhesion kinase signaling regulates anti-inflammatory function of bone marrow mesenchymal stromal cells induced by biomechanical force

“…These native, inherently mechanical, environments direct stem cell differentiation and function [22]. For example, cell culture substrates and scaffolds with bio-inspired topographic features drive MSCs into spatial arrangements that regulate their morphology, stemness, and fate [23–25]. In a recent study, we demonstrated that bone marrow-derived MSCs exposed to wall shear stress (WSS) mimicking vascular biomechanical forces up-regulated anti-inflammatory mediators, including COX2, HO-1, and prostaglandin E 2 (PGE 2 ).…”

2-(Dimethylamino)ethyl Methacrylate/(2-Hydroxyethyl) Methacrylate/α-Tricalcium Phosphate Cryogels for Bone Repair, Preparation and Evaluation of the Biological Response of Human Trabecular Bone-Derived Cells and Mesenchymal Stem Cells

“…The tricalcium phosphate incorporation on cryogels does not affect significantly the Gꞌ value of the cryogels, indicating that new crosslinks are not induced, as it has been described for other systems [12,36]. Despite this fact, an improvement in the biological response of the cryogels has been found as a result of the ceramic incorporation.…”

“…While samples containing 50% and 75% of HEMA started to show a tendency to loss mass after 21 days. Despite cryogels with a greater content in PDMAEMA, (25 HD) provide with a greater Q, that may favor cell penetration [12], samples containing higher DMAEMA amounts showed poorer mechanical properties and degraded after 7 or 14 days, for samples 25 HDT and 25 HD, respectively, showing that samples containing higher amounts of DMAEMA are not suitable for bone repair applications. …”

“…This technique has been successfully employed for the creation of porous systems used as chromatographic columns to capture enzymes [6], as bioreactors [7], in water purification [8] bioengineering [9] and tissue engineering applications [10,11]. Recently, its application in the preparation of scaffolds for bone regeneration by including bioactive ceramic particles to a poly(hydroxyethyl methacrylate) (PHEMA)/polyacrylic acid system has been reported [12].…”

“…In addition, ceramic loading of cryogels has proven to provide appropriate biological cues to promote calcified matrix deposition for the regeneration of calcified tissues [12]. However, before assessing the potential for cell encapsulation in the proposed system some parameters, such as adequate polymer ratio or need for a ceramic component have to be established.…”