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Bone regeneration remains a clinical challenge with limited bone substitutes, urging for effective alternative strategies. Nanotubes, especially carbon nanotubes and titanium dioxide nanotubes, have been widely utilized for bone regeneration; however, their further applications were limited by the composition and degradability. As naturally occurring aluminosilicate nanoclay, halloysite nanotubes (HNTs), with good biocompatibility, functionality, and nanotubular structures, may be a promising platform for promoting bone regeneration. Herein, we presented a HNTs incorporated hydrogel and explored the potential bone tissue engineering applications of HNTs. The HNTs encapsulated hydrogel was simply fabricated by using the photopolymerization method with gelatin methacrylate (GelMA) and HNTs. The incorporation of HNTs led to an enhanced mechanical performance while maintaining a good cytocompatibility in vitro. The osteogenic activities of the HNTs incorporated platform have also been studied in vitro and in vivo. Remarkably, the addition of HNTs obviously upregulated the expression of osteogenic differentiation-related genes and concomitant protein of human dental pulp stem cells (hDPSCs) and therefore facilitated subsequent bone regeneration in calvarial defects of rats. Overall, the results obtained in this study highlight the bone regeneration capacity of HNTs, which may enhance current understanding of HNTs, and present a promising alternative strategy for bone regeneration.

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Rotator cuff injury causes pain in the shoulder and is a challenge to be repaired even after surgical reconstruction. Here, we developed a dual-factor releasing hydrogel based on sulfhydrylated chitosan to deliver KGN and FGF-2 to the injured area to enable fast healing of the tendon–bone interface, which is essential for the repair of rotator cuff injury. We found that the two factors could be easily loaded into the hydrogel, which could in turn continuously release the factors in physiological conditions. The hydrogel was found to be a porous structure through a scanning electron microscope (SEM). The micropores in the hydrogel structure enable the loading and releasing of these molecules. This study showed that KGN and FGF-2 could play a synergistic effect by recruiting and promoting stem cell proliferation and chondrogenesis, thus accelerating the healing of the tendon–bone interface. An in vivo study based on a rabbit rotator cuff injury model demonstrated that the dual-factor releasing hydrogel possesses superior repair capacity than a single-factor releasing hydrogel and the untreated groups. In conclusion, the KGN and FGF-2 dual-factor releasing hydrogel could be a promising biomaterial for the regeneration of the tendon–bone interface and rotator cuff injury repair.

Rotator cuff tears (RCTs) are common in shoulder disease and disability. Despite significant advances in surgical repair techniques, 20–70% of patients still have postoperative rotator cuff dysfunction. These functional defects may be related to retear or rotator cuff quality deterioration due to tendon retraction and scar tissue at the repair site. As an effective delivery system, hydrogel scaffolds may improve the healing of RCTs and be a useful treatment for irreparable rotator cuff injuries. Although many studies have tested this hypothesis, most are limited to laboratory animal experiments. This review summarizes differences in hydrogel scaffold construction, active ingredients, and application methods in recent research. Efforts to determine the indications of hydrogel scaffolds (with different constructions and cargos) for various types of RCTs, as well as the effectiveness and reliability of application methods and devices, are also discussed.

Background. The cell regeneration and blood supply of bone defect lesions are restricted under osteoporotic pathological conditions, which make the healing of bone defect of osteoporosis still a great challenge. The current therapeutic strategies that mainly inhibit bone resorption are not always satisfactory for osteoporotic bone defects, which make the development of new therapies an urgent need. Methods. Previously, we prepared chitosan/nanohydroxyapatite (CS/nHA) biomimetic nanocomposite scaffolds for controlled delivery of bone morphogenetic protein 2-derived peptide (P24). In this study, we determined the effect of coculturing adipose-derived stromal cells (ADSCs) and human umbilical vein endothelial cells (HUVECs) with the CS-P24/nHA nanocomposite scaffolds on osteoporotic bone defect healing. In vitro mixed coculture models were employed to assess the direct effects of coculture. Results. ADSCs cocultured with HUVECs showed significantly greater osteogenic differentiation and mineralization compared with ADSCs or HUVECs alone. The CS-P24/nHA scaffold cocultured with ADSCs and HUVECs was more effective in inducing osteoporotic bone repair, as demonstrated by micro-computed tomography and histology of critical-sized calvariae defects in ovariectomized rats. Calvariae defects treated with the CS-P24/nHA nanocomposite scaffold plus ADSC/HUVEC coculture had a greater area of repair and better reconstitution of osseous structures compared with defects treated with the scaffold plus ADSCs or the scaffold plus HUVECs after 4 and 8 weeks. Conclusion. Taken together, coculture of ADSCs and HUVECs with the CS-P24/nHA nanocomposite scaffold is an effective combination to repair osteoporotic bone defects.