As major complications of chemoradiotherapy, myelosuppression and hematopoietic-system damage severely affect immunologic function and can delay or even terminate treatment for cancer patients. Although several specific cytokines have been used for hematopoiesis recovery, their effect is limited, and they may increase the risk of tumor recurrence. In this study, osteogenic growth peptide functionalized tetrahedral framework nucleic-acid nanostructures (OGP-tFNAs) are prepared; they combine the positive hematopoiesis stimulating effect of OGP and the drug carrying function of tFNAs. The potential of OGP-tFNAs for hematopoietic stimulation and microenvironment regulation is investigated. It is shown that OGP-tFNAs can protect bone marrow stromal cells from 5-fluorouracil (5-FU)-induced DNA damage and apoptosis. OGP-tFNAs pretreatment activates the extracellularly regulated protein kinase signal and downregulates apoptosis-related proteins. OGP-tFNAs also alleviate the chemotherapy-induced inhibition of hematopoiesis-related cytokine expression, which is crucial for hematopoiesis reconstitution. In conclusion, OGP-tFNAs can protect hematopoietic cells and their microenvironment from chemotherapy-induced injuries and myelosuppression, while promoting hematopoiesis regeneration.

Osteonecrosis of the femoral head (ONFH) is recognized as a common refractory orthopedic disease that causes severe pain and poor quality of life in patients. Puerarin (Pue), a natural isoflavone glycoside, can promote osteogenesis and inhibit apoptosis of bone mesenchymal stem cells (BMSCs), demonstrating its great potential in the treatment of osteonecrosis. However, its low aqueous solubility, fast degradation in vivo, and inadequate bioavailability, limit its clinical application and therapeutic efficacy. Tetrahedral framework nucleic acids (tFNAs) are promising novel DNA nanomaterials in drug delivery. In this study, tFNAs as Pue carriers is used and synthesized a tFNA/Pue complex (TPC) that exhibited better stability, biocompatibility, and tissue utilization than free Pue. A dexamethasone (DEX)‐treated BMSC model in vitro and a methylprednisolone (MPS)‐induced ONFH model in vivo is also established, to explore the regulatory effects of TPC on osteogenesis and apoptosis of BMSCs. This findings showed that TPC can restore osteogenesis dysfunction and attenuated BMSC apoptosis induced by high‐dose glucocorticoids (GCs) through the hedgehog and Akt/Bcl‐2 pathways, contributing to the prevention of GC‐induced ONFH in rats. Thus, TPC is a promising drug for the treatment of ONFH and other osteogenesis‐related diseases.

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.

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