With the in-depth understanding of bone regeneration mechanisms and the development of bone tissue engineering, a variety of scaffold carrier materials with desirable physicochemical properties and biological functions have recently emerged in the field of bone regeneration. Hydrogels are being increasingly used in the field of bone regeneration and tissue engineering because of their biocompatibility, unique swelling properties, and relative ease of fabrication. Hydrogel drug delivery systems comprise cells, cytokines, an extracellular matrix, and small molecule nucleotides, which have different properties depending on their chemical or physical cross-linking. Additionally, hydrogels can be designed for different types of drug delivery for specific applications. In this paper, we summarize recent research in the field of bone regeneration using hydrogels as delivery carriers, detail the application of hydrogels in bone defect diseases and their mechanisms, and discuss future research directions of hydrogel drug delivery systems in bone tissue engineering.

Our previous finding revealed that the Wnt10b RNA expression of osteoporotic adipose‐derived stem cells (OP‐ASCs) with impaired osteogenic capacity was significantly reduced than that of ASCs. There are no ideas that the relationship between the OP‐ASCs' impaired osteogenic potential and Wnt10b expression. This study aimed to indicate the potential molecular mechanisms and functional role of Wnt10b in OP‐ASCs, as well as to investigate a potential application to reverse the OP‐ASCs' impaired osteogenic differentiation potential. The OP‐ASCs and ASCs were harvested from the inguinal fat of osteoporosis (OP) mice with bilateral ovariectomy (OVX) and normal mice. qPCR and WB were used to detect the different levels of the expression of the Wnt10b RNA in both OP‐ASCs and ASCs. Lentiviral‐mediated regulation of Wnt10b expression was employed for OP‐ASCs, and the detection of the expression levels of key molecules in the Wnt signalling pathway and key osteogenic factors was performed through qPCR and WB in vitro experiments. The capacity of OP‐ASCs to osteogenesis was determined using alizarin red staining. Lastly, the repair effect of the BCP scaffolds incorporating modified OP‐ASCs on the critical‐sized calvarial defects (CSCDs) in OP mice was scanned and detected by micro‐computed tomography, haematoxylin and eosin staining, Masson's trichrome staining and immunohistochemistry. First, we discovered that both the RNA and protein expression levels of Wnt10b were significantly lower in OP‐ASCs than that in ASCs. In vitro experiments, upregulation of Wnt10b could activate the Wnt signalling pathway, and increase expression of β‐catenin, Lef1, Runx2 and osteopontin (Opn), thereby enhancing the osteogenic ability of OP‐ASCs. In addition, the OP‐ASCs with Wnt10b‐overexpressing could promote the repair of CSCD in osteoporotic mice with increasing new bone volume, bone mineral density, and increased expression of Opn in new bone in vivo. Taken together, overexpression of Wnt10b could partially facilitate the differentiation of OP‐ASCs towards osteogenesis and accelerated the healing of bone defects by activating the Wnt/β‐catenin signalling pathway in vitro and in vivo experiments. This study confirmed the important role of Wnt10b in regulating the osteogenic differentiation capability of OP‐ASCs and indicated Wnt10b could be a potential therapeutic target for reversing the impaired osteogenic capabilities of OP‐ASCs to therapy bone defects of OP patients.

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Diabetes microenvironment will accelerate the accumulation of Advanced glycation end products (AGEs), therefore, AGEs are a signature product in the study of the diabetes microenvironment. Adipose-derived stem cells (ASCs) have poor osteogenesis in the diabetes microenvironment, but the mechanism of the altered osteogenic potential of ASCs has not been elucidated. Bone tissue engineering by ASCs is widely used in the treatment of bone defects with diabetic osteoporosis. Therefore, this study investigated the effects of AGEs on osteogenic differentiation potential of ASCs and the underlying mechanisms. In the present study, we isolated and cultured ASCs in C57BL/6 mice, then treated ASCs with AGEs, the levels of autophagy and osteogenesis-related factors were decreased in the AGE-treated group. In order to verify autophagy and AGE-mediated changes in the osteogenic capacity of ASCs, we used 3-methyladenine, and rapamycin. After cotreatment with 3-methyladenine and AGEs, the levels of osteogenesis and autophagy were reduced more significantly, whereas rapamycin ameliorated the autophagy level and osteogenic differentiation potential of ASCs treated with AGEs. This study shows that AGEs can reduce the osteogenic differentiation potential of ASCs through autophagy, which may provide a reference for the treatment of bone defects with diabetes osteoporosis.