Abstract
A hydrogel based on chitosan, collagen, hydroxypropyl-γ-cyclodextrin and polyethylene glycol was developed and characterized. The incorporation of nano-hydroxyapatite and pre-encapsulated hydrophobic/hydrophilic model drugs diminished the porosity of hydrogel from 81.62 ± 2.25% to 69.98 ± 3.07%. Interactions between components of hydrogel, demonstrated by FTIR spectroscopy and rheology, generated a network that was able to trap bioactive components and delay the burst delivery. The thixotropic behavior of hydrogel provided adaptability to facilitate its implantation in a minimally invasive way. Release profiles from microspheres included or not in hydrogel revealed a two-phase behavior with a burst- and a controlled-release period. The same release rate for microspheres included or not in the hydrogel in the controlled-release period demonstrated that mass transfer process was controlled by internal diffusion. Effective diffusion coefficients, Deff, that describe internal diffusion inside microspheres, and mass transfer coefficients, h, i.e. the contribution of hydrogel to mass transfer, were determined using ‘genetic algorithms’, obtaining values between 2.64·10−15 and 6.67·10−15 m2/s for Deff and 8.50·10−10 to 3.04·10−9 m/s for h. The proposed model fits experimental data, obtaining an R2-value ranged between 95.41 and 98.87%. In vitro culture of mesenchymal stem cells in hydrogel showed no manifestations of intolerance or toxicity, observing an intense proliferation of the cells after 7 days, being most of the scaffold surface occupied by living cells.
Highlights
Hydrogels are three-dimensional hydrophilic polymeric networks, which are able to absorb and retain large quantities of water, solvents or biological fluids in the free space of their structure without being dissolved in the same media
An innovative thixotropic hydrogel based on chitosan, collagen, HP-c-CD and polyethylene glycol (PEG) has been developed
In order to target its use in bone regeneration, the hydrogel incorporated nano-hydroxyapatite and microspheres loaded with hydrophobic or hydrophilic model drugs (17-b-estradiol or RITC-dextran) that slightly diminished the porosity of hydrogel to 69.98 6 3.07%
Summary
Hydrogels are three-dimensional hydrophilic polymeric networks, which are able to absorb and retain large quantities of water, solvents or biological fluids in the free space of their structure without being dissolved in the same media. The high permeability and porosity of hydrogels facilitates, integration in the majority of tissues, and incorporation by the cells, and their biocompatibility and biodegradation avoid surgery to remove polymer after treatment [2, 3] Their similarity to the extracellular matrix or tissues, low interfacial tension between gel and solvents, and minimal irritation after application due to their water content and soft nature [2, 3] have made hydrogels the ideal candidates for biomedical and pharmaceutical applications, such as implants and sutures, wound dressings, controlled drug delivery, diagnostic imaging, medical and biological sensors or microfluidics [3, 4]. Rheology of this type of hydrogels provides adaptability to the shape of the area to be treated, an easy ‘in vivo’ implantation in a minimally invasive way and capacity to incorporate bioactive substances and/or cells
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