Abstract
Accumulating evidence has suggested the significant potential of chemically modified hydrogels in bone regeneration. Despite the progress of bioactive hydrogels with different materials, structures and loading cargoes, the desires from clinical applications have not been fully validated. Multiple biological behaviors are orchestrated precisely during the bone regeneration process, including bone marrow mesenchymal stem cells (BMSCs) recruitment, osteogenic differentiation, matrix calcification and well-organized remodeling. Since matrix metalloproteinases play critical roles in such bone metabolism processes as BMSC commitment, osteoblast survival, osteoclast activation matrix calcification and microstructure remodeling, matrix metalloproteinase (MMP) cleavable peptides-based hydrogels could respond to various MMP levels and, thus, accelerate bone regeneration. In this review, we focused on the MMP-cleavable peptides, polymers, functional modification and crosslinked reactions. Applications, perspectives and limitations of MMP-cleavable peptides-based hydrogels for bone regeneration were then discussed.
Highlights
Bone tissue regeneration in orthopedic and maxillofacial surgery remains a common challenge [1]
The results show that the hydrogel can induce MSCs to differentiate into chondrocytes, and customize the phenotype and matrix production pattern of differentiated cells according to the specific region of articular cartilage by changing the material composition
Hydrogels composed of peptide (CVPLS↓LYSGC) are susceptible to matrix metalloproteinase (MMP)-14 and have a faster degradation compared with the hydrogels that possess the peptide (CRGRIGF↓LRTDC), resulting in faster cell migration as well as accelerated early osteogenesis
Summary
Bone tissue regeneration in orthopedic and maxillofacial surgery remains a common challenge [1]. Numerous studies have recently introduced bioactive scaffolds and their interaction with adjacent bony tissues, and hydrogels have received attention due to their excellent biocompatibility, biodegradability and plasticity [7,8,9] With their hydrophilic polymeric networks, hydrogels are considered the most promising polymer scaffold in bone tissue engineering [10], and the modification of their permeability and stiffness enables substance exchanges and cell function [11,12]. The GCRD sequence was utilized to synthesize the GCRD-VPMS↓MRGG-DRCG complex In this regard, the water-solubility of the peptide was upregulated via the hydrophilic arginine (R), and the thiol group-based crosslinker was introduced due to the existence of cysteine (C), glycine (G) and aspartic acid (D) as spacers [17]. MMP-cleavable peptides have exhibited exciting potential for biomedical tissue engineering
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