Development and In Vivo Assessment of an Injectable Cross‐Linked Cartilage Acellular Matrix‐PEG Hydrogel Scaffold Derived from Porcine Cartilage for Tissue Engineering

Abstract

The cartilage acellular matrix (CAM) derived from porcine cartilage, which does not induce significant inflammation and provides an environment conducive for cell growth and differentiation, is a promising biomaterial candidate for scaffold fabrication. However, the CAM has a short period in vivo, and the in vivo maintenance is not controlled. Therefore, this study is aimed at developing an injectable hydrogel scaffold using a CAM. The CAM is cross‐linked with a biocompatible polyethylene glycol (PEG) cross‐linker to replace typically used glutaraldehyde (GA) cross‐linker. The cross‐linking degree of cross‐linked CAM by PEG cross‐linker (Cx‐CAM‐PEG) according to the ratios of the CAM and PEG cross‐linker is confirmed by contact angle and heat capacities measured by differential scanning calorimetry. The injectable Cx‐CAM‐PEG suspension exhibits controllable rheological properties and injectability. Additionally, injectable Cx‐CAM‐PEG suspensions with no free aldehyde group are formed in the in vivo hydrogel scaffold almost simultaneously with injection. In vivo maintenance of Cx‐CAM‐PEG is realized by the cross‐linking ratio. The in vivo formed Cx‐CAM‐PEG hydrogel scaffold exhibits certain host–cell infiltration and negligible inflammation within and near the transplanted Cx‐CAM‐PEG hydrogel scaffold. These results suggest that injectable Cx‐CAM‐PEG suspensions, which are safe and biocompatible in vivo, represent potential candidates for (pre‐)clinical scaffolds.

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

“…Ju and colleagues used the dECM derived from porcine cartilage to crosslink with PEG and prepared an injectable suspension, which could form hydrogel scaffolds in situ after injection. 173 This hydrogel was proved to be a safe implantation and was endowed with better bio-activity, as it exhibited improved host-cell infiltration and prolonged retention time in vivo . According to the report of Li et al , the addition of hydroxypropyltrimethyl ammonium chloride chitosan (HACC) into benzaldehyde-terminated PEG gave this hydrogel the ability to significantly accelerate wound healing by inhibiting bacteria, and promoting host cell migration and proliferation.…”

Cryopreservation of Cell Sheets for Regenerative Therapy: Application of Vitrified Hydrogel Membranes

“…PEG has been used as a medical material for a long time. PEG-based materials are the most well-known DDS carriers made of PEG [ 68 , 69 , 70 ]. They can improve blood retention and enhance drug efficacy, but are not biodegradable or cell-adhesive.…”

Fabrication and Validation of a 3D Portable PEGDA Microfluidic Chip for Visual Colorimetric Detection of Captured Breast Cancer Cells

“…In particular, the chips can be used to closely simulate the physiological microenvironment and cell interactions in vivo [7,8]. 2-Hydroxyethyl methacrylate (HEMA) and polyethylene glycol (PEG), as bases for hydrogel chips, are broadly studied materials [9,10] and represent novel tools for biomedical and tissue engineering applications due to their non-toxic and nonimmunogenic characteristics, excellent biocompatibility, and tunable physical properties as well as their high surface modification capacity [11,12]. PEG-based hydrogel scaffolds are capable of supporting three-dimensional (3D) cell and tissue growth within crosslinks [13].…”