Composite Cryogel with Polyelectrolyte Complexes for Growth Factor Delivery

Abstract

Macroporous scaffolds composed of chitosan (CHI), hydroxyapatite (HA), heparin (Hep), and polyvinyl alcohol (PVA) were prepared with a glutaraldehyde (GA) cross-linker by cryogelation. Addition of PVA to the reaction mixture slowed down the formation of a polyelectrolyte complex (PEC) between CHI and Hep, which allowed more thorough mixing, and resulted in the development of the homogeneous matrix structure. Freezing of the CHI-HA-GA and PVA-Hep-GA mixture led to the formation of a non-stoichiometric PEC between oppositely charged groups of CHI and Hep, which caused further efficient immobilization of bone morphogenic protein 2 (BMP-2) possible due to electrostatic interactions. It was shown that the obtained cryogel matrix released BMP-2 and supported the differentiation of rat bone marrow mesenchymal stem cells (rat BMSCs) into the osteogenic lineage. Rat BMSCs attached to cryogel loaded with BMP-2 and expressed osteocalcin in vitro. Obtained composite cryogel with PEC may have high potential for bone regeneration and tissue engineering applications.

Physically Crosslinked Poly (Vinyl Alcohol)/Kappa-Carrageenan Hydrogels: Structure and Applications

“…The hydrogels exhibiting higher media penetration velocities (i.e., permeability) also presented higher values for the equilibrium swelling degree. The early-time and late-time diffusion coefficients calculated from Equations (12) and (13) reported in Table 4 range from 5.42 10 −5 to 8.97 10 −4 mm 2 /min, respectively 0.0879 to 0.480 mm 2 /min, increasing in the same manner as the solvent penetration rate ν. The relatively high values for the diffusion coefficients are comparable to other PVA-containing hydrogels [75,76], and imply a high degree of polymer chains relaxation (this could also be deducted from the values of n, which range from 0.73 to 1.00).…”

“…Many polysaccharides, in their natural or chemically functionalized state, such as chitosan, starch, dextran, cellulose, xanthan, β-glucans, sodium alginate, carrageenans and so forth, have been previously blended with PVA to obtain cryogels [11,12]. Due to their overall hydrophilic character, the addition of polysaccharides (e.g., starch, hydroxyethyl starch) can increase the swelling degree of the blend cryogels up to 300% compared with neat PVA, submitted to identical physical crosslinking operational parameters [13,14].…”

Sequential Delivery of Cryogel Released Growth Factors and Cytokines Accelerates Wound Healing and Improves Tissue Regeneration

“…Cryogels were prepared as previously described (Sultankulov et al, 2019a). Briefly, 2% w/v Chitosan (Sigma, United States) was solubilized in 1% v/v acetic acid (Millipore, United States) and 5% w/v polyvinyl alcohol (PVA, Sigma, United States) was dissolved in deionized H 2 O on a heating plate using a magnetic stirrer for 1-2 h. For the preparation of cryogel, 5 ml of PVA, 5 ml of heparin (Sigma, United States), 10 ml of chitosan and 0.5% v/v glutaraldehyde (GA) (Sigma, United States) were sequentially added and mixed using a magnetic stirrer.…”

“…Another recent development in drug delivery systems is cryogel, which is a modified form of hydrogel with the advantage of manipulating pore sizes, allowing for the passage of blood vessels and cells (Leach et al, 2019;Shah et al, 2019;Sultankulov et al, 2019b). It can be fabricated from both natural and synthetic polymers and has a wide range of tissue engineering applications, including bioreactors (Berillo et al, 2019), cell separation (Kumar and Srivastava, 2010), skin (Allan et al, 2016), cartilage (Han et al, 2016), bone (Kemençe and Bölgen, 2017;Sultankulov et al, 2019a), neural (Singh et al, 2018), and muscle tissue repair (Leach et al, 2019;Shah et al, 2019). Moreover, cryogels could be made using biopolymers with intrinsic antimicrobial activity, such as chitosan (Khan et al, 2019).…”

“…To test this hypothesis, we utilized a novel chitosan-based cryogel that was composed of chitosan and heparin, and possessed high porosity and interconnective pore morphology. The chitosanbased cryogel was previously characterized and demonstrated the ability to incorporate and release bone morphogenic protein 2 for supporting the differentiation of mesenchymal stem cells into the osteogenic lineage (Sultankulov et al, 2019a). Chitosan is a positively charged polymer with the ability to form a polyelectrolyte complex with heparin, which makes incorporation of factors possible due to electrostatic interactions.…”