Injectable, In Situ Self-cross-linking, Self-healing Poly(l-glutamic acid)/Polyethylene Glycol Hydrogels for Cartilage Tissue Engineering

Abstract

Injectable hydrogels have drawn much attention in the field of tissue engineering because of advantages such as simple operation, strong plasticity, and good biocompatibility and biodegradability. Herein, we propose the novel design of injectable hydrogels via a Schiff base cross-linking reaction between adipic dihydrazide (ADH)-modified poly(l-glutamic acid) (PLGA-ADH) and benzaldehyde-terminated poly(ethylene glycol) (PEG-CHO). The effects of the mass fraction and the molar ratio of −CHO/–NH2 on the gelation time, mechanical properties, equilibrium swelling, and in vitro degradation of the hydrogels were examined. The PLGA/PEG hydrogels cross-linked by dynamic Schiff base linkages exhibited good self-healing ability. Additionally, the PLGA/PEG hydrogels had good biocompatibility with bone marrow-derived mesenchymal stem cells (BMSCs) and could effectively support BMSC proliferation and deposition of glycosaminoglycans and upregulate the expression of cartilage-specific genes. In a rat cartilage defect model, PLGA/PEG hydrogels significantly promoted new cartilage formation. The results suggest the prospect of the PLGA/PEG hydrogels in cartilage tissue engineering.

Injectable smart stimuli-responsive hydrogels: pioneering advancements in biomedical applications

“…192 Li et al designed a novel injectable hydrogel with self-healing ability based on the Schiff base reaction between benzaldehyde-terminated PEG (PEG-CHO) and adipic dihydrazide-modified PLGA (PLGA-ADH), which exhibited favorable support towards the proliferation of BMSCs and the deposition of GAGs in a rat cartilage defect model. 193 Recently, interest has also been raised in designing smart PLGA-based hydrogels, which can respond to specific endogenous and/or exogenous stimuli, to further develop targeted therapy and precision medicine. A thermo-responsive PLGA-PEG-PLGA hydrogel encapsulating interleukin-36 receptor antagonist (IL-36Ra) was prepared by Yi et al , which could gel rapidly after intra-articular injection, release IL-36Ra slowly over a prolonged period, up-regulate the expression of collagens and GAGs while down-regulating that of MMP-13 and ADAMTS-5.…”

Tailoring biomaterials for biomimetic organs-on-chips

“…In addition, the adjustable mechanical and chemical properties of PEG make it a popular biomaterial in the field of tissue engineering and organs-on-chips. 89–91 Other hydrophilic polymers like polyacrylamide, 92 polyvinyl alcohol (PVA), 93 and polyurethane (PU) 94 have also exhibited their potential in supporting and facilitating the growth of organ cells. In the fabrication of microfluidic chips, polydimethylsiloxane (PDMS), a silicon-based organic polymer, is widely applied owing to its high transparency, adjustable flexibility, and favorable biocompatibility.…”

Micelle–Micelle Cross-Linked Highly Stretchable Conductive Hydrogels for Potential Applications of Strain and Electronic Skin Sensors

“…40,41 Here, L-glutamic acid (LGA) was applied as a source of cross-linker, and in many studies the LGA was polymerized and produced efficiently hydrogels for various types of applications. 42,43 LGA is an alpha amino acid that is naturally produced in the human body through the synthesis of arginine and proline. This amino acid plays a crucial role in the body, as it can be converted to glutamine and serves as a precursor for collagen, a protein vital for tissue regeneration.…”

“…Currently, electrostatic interactions are the important and strong interactions that are highly used to prepared, highly resilient, and tough hydrogels for numerous applications. , These interactions come about due to the oppositely charge species (positive and negative) which attract one another for physical attraction and play a key role in the dissipation of energy when external loads have been applied. As electrostatic interactions are physical and reversible in nature, these interactions autonomously reconstruct when the load has been removed. , Here, l -glutamic acid (LGA) was applied as a source of cross-linker, and in many studies the LGA was polymerized and produced efficiently hydrogels for various types of applications. , LGA is an alpha amino acid that is naturally produced in the human body through the synthesis of arginine and proline. This amino acid plays a crucial role in the body, as it can be converted to glutamine and serves as a precursor for collagen, a protein vital for tissue regeneration.…”