Effects of Calcium Carbonate Microcapsules and Nanohydroxyapatite on Properties of Thermosensitive Chitosan/Collagen Hydrogels

Abstract

Thermosensitive chitosan/collagen hydrogels are osteoconductive and injectable materials. In this study, we aimed to improve these properties by adjusting the ratio of nanohydroxyapatite particles to calcium carbonate microcapsules in a β-glycerophosphate-crosslinked chitosan/collagen hydrogel. Two hydrogel systems with 2% and 5% nanohydroxyapatite particles were studied, each of which had varying microcapsule content (i.e., 0%, 1%, 2%, and 5%). Quercetin-incorporated calcium carbonate microcapsules were prepared. Calcium carbonate microcapsules and nanohydroxyapatite particles were then added to the hydrogel according to the composition of the studied system. The properties of the hydrogels, including cytotoxicity and biocompatibility, were investigated in mice. The calcium carbonate microcapsules were 2–6 µm in size, spherical, with rough and nanoporous surfaces, and thus exhibited a burst release of impregnated quercetin. The 5% nanohydroxyapatite system is a solid particulate gel that supports homogeneous distribution of microcapsules in the three-dimensional matrix of the hydrogels. Calcium carbonate microcapsules increased the mechanical and physical strength, viscoelasticity, and physical stability of the nanohydroxyapatite hydrogels while decreasing their porosity, swelling, and degradation rates. The calcium carbonate microcapsules–nanohydroxyapatite hydrogels were noncytotoxic and biocompatible. The properties of the hydrogel can be tailored by adjusting the ratio of calcium carbonate microcapsules to the nanohydroxyapatite particles. The 1% calcium carbonate microcapsules containing 5% nanohydroxyapatite particle–chitosan/collagen hydrogel exhibited mechanical and physical strength, permeability, and prolonged release profiles of quercetin, which were superior to those of the other studied systems and were optimal for promoting bone regeneration and delivering natural flavonoids.

Recent Development of Functional Chitosan-Based Hydrogels for Pharmaceutical and Biomedical Applications

“…This system is able to promote osteogenic differentiation, allowing bone regeneration both in vitro and in vivo [ 205 ]. For natural product delivery to treat bone disease, calcium carbonate microcapsules containing nanohydroxyapatite particle/chitosan/collagen hydrogel have the prolonged release profiles of quercetin, which has been proven for promoting bone regeneration and delivering natural flavonoids [ 206 ]. For RA, deoxyribonuclease I (DNase)/oxidized hyaluronic acid/CMC is injectable, degradable, and biocompatible that also reduces inflammatory cytokine expression for alleviating RA symptoms [ 207 ].…”

Chitosan-Based Smart Biomaterials for Biomedical Applications: Progress and Perspectives

“…128 Furthermore, the potency of the combination of chitosan, hydroxyapatite, βGP, as thermosensitive hydrogels, was also revealed by another study with the addition of calcium carbonate and collagen to be applied to a well-defined bony defect. 129 The increasing of the βGP content will increase the bonding of the functional group and also influence the setting time of transformation. 129 However, the increasing of the βGP content can induce the toxicity properties of the scaffolds.…”

“…129 The increasing of the βGP content will increase the bonding of the functional group and also influence the setting time of transformation. 129 However, the increasing of the βGP content can induce the toxicity properties of the scaffolds. 129 One of the ways to minimalize the toxicity of the thermosensitive scaffolds is using a "green" method without an organic solvent to dissolve chitosan.…”

“…The scaffolds material was treated by hydrothermal methods and resulted in good biocompatibility by the evaluation of alkaline phosphatase (ALP) activity, indicating the potential application for repairing and regenerating bone tissue . Furthermore, the potency of the combination of chitosan, hydroxyapatite, βGP, as thermosensitive hydrogels, was also revealed by another study with the addition of calcium carbonate and collagen to be applied to a well-defined bony defect . The increasing of the βGP content will increase the bonding of the functional group and also influence the setting time of transformation .…”

The Diamond Concept Enigma: Recent Trends of Its Implementation in Cross-linked Chitosan-Based Scaffolds for Bone Tissue Engineering

“…226 For example, Georgopoulou et al used HE and Masson Trichrome stainings to assess the ability of a glutaraldehyde cross-linked chitosan and gelatin scaffold to support bone regeneration and formation of the extracellular matrix. 229 HE staining is one of the primary methods for assessing bone healing in vivo, with a reported usage of 86.2% MicroCT and CT imaging 64,65,77,80,89,100,120,124,131,136,140,141,162,164,185 78.9% X-ray imaging 112,168 10.5% Radiography 83,136 10.5% Scanning electron microscopy 81 5.3% Stereoscopic imaging 81 5.3% Staining techniques 87.9% HE staining 77,80,81,83,86,97,100,106,112,113,[120][121][122]124,131,134,136,140,141,152,159,164,169,…”