Robust tissue growth and angiogenesis in large-sized scaffold by reducing H ₂ O ₂ -mediated oxidative stress

Abstract

The implantation of cell-seeded large-sized scaffold often results in insufficient tissue regeneration, which is still a challenge for successful grafting. Excess hydrogen peroxide (HO) released by cells propagates oxidative stress, which is the primary cause of tissue injury leading to failure in tissue regeneration. Hence, preventing tissue from oxidative damage becomes imperative. For the first time, we entrapped catalase, an antioxidant in a scaffold as a novel approach in bioengineering to prevent tissue from HO-induced damage. The gel prepared from the mixture of decellularized adipose tissue and high viscous sodium alginate was used to entrap the catalase, and was coated to 3D polycaprolactone porous scaffolds. This study showed that our 3D design would regulate the release of catalase in a sustained and efficient manner protecting human turbinate mesenchymal stem cells cultured in 2D/3D in vitro oxidative microenvironment provided by HO, and supporting their robust growth. Interestingly, in vivo study revealed that our design was successful in tissue engineering by both an increase in tissue growth (≥45%) throughout the large-sized scaffold with substantial reduction in inflammation (≥40%), and an increase in the induction of angiogenesis (≥40%). This novel design, therefore, would be highly applicable for successful grafting to replace a damaged tissue in future.

Porcine Breast Extracellular Matrix Hydrogel for Spatial Tissue Culture

“…Hydrogel is a gel formed by networks of polymer chains, which have the ability to retain the water and gelatinize easily through various cross-linking processes. It has a wide range of applications ranging from biomedical research, tissue engineering, and clinical utilization to drug delivery [ 1 , 2 , 3 , 4 ]. Hydrogels are commonly classified into two major categories, synthetic and natural, based on the origin and biochemical properties of the source materials used to produce the gel.…”

Native-mimicking in vitro microenvironment: an elusive and seductive future for tumor modeling and tissue engineering

“…Some synthetic biomaterials like polycarpolactone (PCL) is entirely hydrophobic in nature and difficult to grow cells for tissue engineering and biomedical studies, while some hydrophilic biomaterials such as silk fibroin, aloe vera, and curcumin can be added to PCL to make smart surfaces for cell attachment [ 102 ]. PCL can also be coated with cell-laden ECM, alginate or decellularized ECM, making it more hydrophilic and native-mimicking for cells [ 103 , 104 ]. Furthermore, PCL is one of the most widely used synthetic ECM in various formats of scaffolds for cancer studies because of its slow degradation kinetics and biocompatibility, supporting TME that contain cancer cells [ 105 – 107 ].…”

“…Because of overall low oxygen tensions in human tissues, engineering approaches for tissue repair and regeneration have not been very successful as expected [ 271 ]. To address this challenge, various functional biomaterials, such as oxygen delivery biomaterials, oxygen generating biomaterials, and oxygen releasing biomaterials that provide oxygen and prevent cells from ischemic necrosis, have been developed [ 104 , 272 – 274 ]. On the other hand, hypoxia can enhance mechanical properties of engineered tissues as well as increase angiogenesis and deposition of specific ECM components in cancers.…”

Application of Synthetic Polymeric Scaffolds in Breast Cancer 3D Tissue Cultures and Animal Tumor Models

“…Depending on scientific questions to be addressed and specific experimental design, 3D scaffolds applied in biomedical research are predominantly fabricated using either natural materials, such as native tissue proteins and algae, or synthetic polymers, such as PLGA, PCL, and poly(ethylene glycol) (PEG) [ 7 , 17 , 18 ]. The advantages of synthetic polymeric scaffolds are their abundant availability, low cost, suitability for large-scale 3D bioprinting and reconstruction of certain tissue structures, and flexibility to be tailored to meet specific physical requirements of different culture systems [ 19 – 24 ].…”