Bottom-up engineering of the nucleus pulposus using a photocrosslinkable decellularized matrix hydrogel attenuates inflammaging and enhances microtissue-mediated regeneration
Xiaoxiao Li , Xiangwei Li , Dandan Zhou , Yanqin Xu , Biemin Sun , Yanzhu Hu , Yibo Zhu , Junxian Hu , Zeyu Pang , Chen Zhao , Yongjian Gao , You Long , Pei Li , Qiang Zhou , Yiyang Wang
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引用次数: 0
Abstract
Degenerative disc disease (DDD), characterized by the pathological deterioration of nucleus pulposus (NP) tissue, affects millions globally. Tissue engineering strategies offer potential to create tissue-engineered NP (TE-NP) analogs to address DDD. However, traditional "top-down' approaches face challenges in achieving uniform cell distribution and replicating the intradiscal extracellular matrix (ECM) environment. In contrast, a "bottom-up' strategy utilizing microscale seed units represents a promising alternative. This study introduces an innovative "bottom-up' approach for constructing TE-NP, leveraging bioreactor-cultivated NP microtissues (NP-MTs) as seed units and a novel methacrylate-modified decellularized nucleus pulposus matrix (DNPM-MA) hydrogel as a supporting biomaterial. NP-MTs cultivated under low-magnitude hydrostatic pressure exhibit nascent ECM surroundings adapting well to the intradiscal microenvironment. The DNPM-MA hydrogel, with its compositional and mechanical attributes, supports the growth, migration, proliferation, and ECM synthesis of NP-MTs, making it an ideal biomaterial for long-term cultivation. The combination of NP-MTs and the DNPM-MA hydrogel yielded superior tissue regeneration outcomes both in vitro and in vivo. Transcriptome and molecular assessments revealed a correlation between the biological properties of the DNPM-MA hydrogel and the attenuation of inflammaging within encapsulated NP-MTs. Overall, this innovative "bottom-up' constructed TE-NP exhibits superior regenerative potential and is a promising tissue engineering strategy for treating DDD.
期刊介绍:
Materials Today Bio is a multidisciplinary journal that specializes in the intersection between biology and materials science, chemistry, physics, engineering, and medicine. It covers various aspects such as the design and assembly of new structures, their interaction with biological systems, functionalization, bioimaging, therapies, and diagnostics in healthcare. The journal aims to showcase the most significant advancements and discoveries in this field. As part of the Materials Today family, Materials Today Bio provides rigorous peer review, quick decision-making, and high visibility for authors. It is indexed in Scopus, PubMed Central, Emerging Sources, Citation Index (ESCI), and Directory of Open Access Journals (DOAJ).