Hydrogels are widely used as scaffold in tissue engineering field because of their ability to mimic the cellular microenvironment. However, mimicking a completely natural cellular environment is complicated due to the differences in various physical and chemical properties of cellular environments. Recently, gradient hydrogels provide excellent heterogeneous environment to mimic the different cellular microenvironments. To create hydrogels with an anisotropic distribution, gradient hydrogels have been widely developed by adopting several gradient generation techniques. Herein, the various gradient hydrogel fabrication techniques, including dual syringe pump systems, microfluidic device, photolithography, diffusion, and bio‐printing are summarized. As the effects of gradient 3D hydrogels with stems have been reviewed elsewhere, this review focuses principally on gradient hydrogel fabrication for multi‐model tissue regeneration. This review provides new insights into the key points for fabrication of gradient hydrogels for multi‐model tissue regeneration.
Poly(ethylene arginyl aspartate diglyceride) (PEAD) polycation is widely used to prepare coacervate particles by electrostatic complexation with an anionic heparin (HEP) in aqueous environments, for controlled release of therapeutic proteins. However, coacervate complexes aggregate randomly due to particle–particle charge interactions. Herein, a new term “coacersome” is introduced to represent a stable polyplex formed by complexation of mPEGylated PEAD and HEP. Methoxy polyethylene glycol (mPEG)‐b‐cationic PEAD diblock copolymers are synthesized and complexed with HEP to create a stable “coacersome” structure. Water‐soluble mPEG moiety assembles on the surface of coacersomes in aqueous conditions and creates a steric barrier to avoid aggregation of coacersomes. The coacersomes are able to maintain their initial spherical morphology and size for longer durations in the presence of competing ions, such as 0.3 m NaCl. Additionally, the coacersomes exhibit biocompatibility toward human dermal fibroblasts, a high loading efficiency (>96%) for encapsulation of bone morphogenetic protein 2 (BMP‐2), and a sustained release profile up to 28 days. The BMP‐2‐loaded coacersomes further exhibit increased osteogenic differentiation of human mesenchymal stem cells (hMSCs). The developed coacersome structures have the potential to be utilized as effective carriers for therapeutic protein delivery.
BackgroundSurface functionalization of gold nanoparticles (AuNPs) has emerged as a promising field of research with enormous biomedical applications. The folate (FA)-attached polymer-gold nanoconjugates play vital role in targeting the cancer cells.MethodsAuNPs were synthesized by using di- or tri-carboxylate-polyethylene glycol (PEG) polymers, including citrate-PEG (CPEG), malate-PEG (MAP), and tartrate-PEG (TAP), as a reducing and stabilizing agent. After synthesis of polymer-AuNPs, the freely available hydroxyl and carboxylate groups of CPEG, MAP, and TAP were used to attach a cancer cell-targeting agent, FA, via a 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxy succinimide coupling reaction to obtain FA-CPEG-AuNP, FA-MAP-AuNP, and FA-TAP-AuNP nanocon-jugates, respectively. The 5-fluorouracil (5FU) was attached to π back-bonded carbonyl oxygens of the nanoconjugates, and the in vitro drug release profile was studied by high pressure liquid chromatography. Biocompatibility profiles of the FA-CPEG-AuNP, FA-MAP-AuNP, and FA-TAP-AuNP nanoconjugates were investigated using adult human dermal fibroblasts. Anti-breast cancer activity of 5FU-loaded nanoconjugates was investigated using MCF-7 breast cancer cells.ResultsX-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy analyses confirmed that AuNPs attached to CPEG, MAP, or TAP via the formation of π back bonding between AuNPs and the ester carbonyl group. The π back-bonded nanoconjugates exhibited sustained release of 5FU up to 27 days. FA-MAP-AuNPs exhibited an IC50 at 5 µg/mL, while FA-CPEG-AuNPs and FA-TAP-AuNPs showed the IC50 at 100 µg/mL toward MCF-7 cancer cells.ConclusionThe developed polymer π back-bonded multifunctional gold nanoconjugates could be used as a potential drug delivery system for targeting MCF-7 cancer cells.
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