The Preparation And Application Of A Novel Collagen-based Bioink

Three-dimensional(3D)bioprinting technology has gained more and more attention in the field of tissue engineering based on its remarkable advantages such as high automation,high customizability,and high controllability.Bioink,a biological agent primarily composed of cells and biocompatible materials,is the key material used for 3D bioprinting.The development of bioinks with both good biocompatibility and stable printability still remains a huge challenge.Collagen is the main component of extracellular matrix,which has been widely used in biomedicine.However,factors such as poor mechanical properties,slow curing speed,and difficulty in maintaining bioactivity limit its application in 3D bioprinting.Herein,a collagen-based bioink that can be formed using digital light processing(DLP)technology has been developed,which is expected to be a perfect candidate for 3D bioprinting.First,collagen methacrylate with a typical triple helix structure was successfully synthesized,while the substitution degree of collagen methacrylate was improved to 68.0 % by increasing the p H of the reaction solution.Next,a series of collagen-based bioinks made of collagen methacrylate was prepared,with rapid photo-curing properties under ultraviolet light endowed by a photoinitiator called LAP.At the same time,a small amount of procyanidins(PA)was supplemented to enrich the cross-linking mechanism and improve the mechanical properties,printability,and biocompatibility of ColMA-PA bioinks.With the addition of PA,the storage modulus of ColMA-PA40 hydrogels reached the highest value of 14.3 Pa,which was 10 times of that of pristine hydrogels.Then,these ColMA-PA bioinks were able to construct hydrogels with fine three-dimensional structures using 3D printing technology based on DLP,with maximum printing accuracy up to 200 μm.More importantly,we successfully performed cell-loaded 3D bioprinting with collagen-based bioinks mentioned herein.The L-929 cells were evenly distributed in a customized collagen hydrogel with high proliferation activity.To further prove its great application potential,the collagen-based bioinks were used to construct a trachea in vitro.The collagen tubes with inner diameters ranging from 100 μm to 6 mm were fabricated and the endothelialization of the lumen was determined by in vitro experiments.These properties have proven that the collagen-based bioinks developed here not only meets the needs of high-accuracy printing but also allows cell adhesion and proliferation,demonstrating a balance between biocompatibility and printability.This project realized 3D bioprinting of collagen in a simple and universal way,broke through the limitations of collagen,expanded the bioinks reservoir,and provided a new path for researchers with 3D bioprinting needs,showing great potential for biomedical applications.