Nucleotomy, a surgical procedure employed to address nucleus pulposus (NP) herniation, frequently results in defects within the annulus fibrosus (AF). Owing to the inherently limited self-repair ability of AF tissue, untreated lesions may precipitate reherniation of the NP, thereby accelerating the degeneration of the intervertebral disc. In this study, we introduce a novel composite scaffold comprising hydrogel-reinforced electrospun nanofibers, engineered to mimic the heterogeneous microarchitecture of the native AF matrix while offering improved mechanical support. A mesh-like polycaprolactone (PCL)/gelatin methacryloyl (GelMA) hybrid electrospun nanofibrous membrane was designed to replicate the AF outer region, while a hydrogel mixture of fucoidan methacryloyl (FuMA) and GelMA was sprayed to the membrane surface to emulate the inner region. The integrated FuMA/GelMA hydrogel and PCL/GelMA nanofiber layer enhanced the proliferation of AF cells and markedly improved the synthesis of AF matrix components. Importantly, even under oxidative stress induced by hydrogen peroxide, this hydrogel-reinforced nanofibrous composite effectively maintained the mitochondrial functions of AF cells, thereby supporting their energy metabolism and matrix anabolism. Further molecular experiments unraveled that this composite protected AF cells from oxidative damage through activation of the NRF2-mediated antioxidant enzymes, such as heme oxygenase 1. In a rat caudal disc box defect model, the implantation of a hydrogel-reinforced nanofibrous composite promoted the regeneration of AF tissue, preserved the hydration of NP tissue, and inhibited intervertebral disc degeneration. This approach represents a promising strategy for the repair of nucleotomy-induced AF damage, thereby offering potential therapeutic benefits for patients experiencing intervertebral disc degeneration.

Bone defect repair continues to present a significant clinical challenge due to the limitations of traditional grafting techniques and the complexity involved in establishing a conducive regenerative microenvironment. In this study, we described the development of a multifunctional biomimetic periosteum based on electrospun gelatin methacryloyl (GelMA) membranes functionalized with bone morphogenetic protein-2 (BMP-2)-loaded M2 macrophage-derived exosomes. This engineered periosteum replicated the structural orientation and functional properties of natural periosteum, thereby providing a synergistic approach to promoting bone regeneration. Our findings indicated that the biomimetic periosteum served as a biocompatible scaffold that supported cell adhesion, proliferation, and differentiation. The incorporation of M2 macrophage-derived exosomes facilitated the creation of an anti-inflammatory immune microenvironment by polarizing macrophages towards the M2 phenotype, while the sustained release of BMP-2 enhances osteogenic differentiation and mineralization. In vivo experiments using a rat cranial defect model demonstrated that the BMP-2@Exo-GelMA membrane significantly accelerated bone defect repair, achieving superior outcomes in new bone formation and vascularization compared to control groups. This study underscored the potential of integrating immunomodulatory and osteoinductive strategies to develop next-generation biomaterials for bone tissue engineering. The biomimetic periosteum represented a promising therapeutic approach for addressing critical-sized bone defects and advancing clinical practices in bone regeneration.

Intervertebral disc (IVD) herniation is a major cause of chronic low back pain and disability. The current nucleus pulposus (NP) discectomy effectively relieves pain symptoms, but the annulus fibrosus (AF) defects are left unrepaired. Tissue engineering approaches show promise in treating AF injury and IVD degeneration; however, the presence of an inflammatory milieu at the injury site hinders the mitochondrial energy metabolism of AF cells, resulting in a lack of AF regeneration. In this study, we fabricated a dynamic self-healing hydrogel loaded with melatonin (an endocrine hormone well-known for its antioxidant and anti-inflammatory properties) and investigate whether melatonin-loaded hydrogel could promote AF defect repair by rescuing the matrix synthesis and energy metabolism of AF cells. The protective effects of melatonin on matrix components (e.g. type I and II collagen and aggrecan) in AF cells were observed in the presence of interleukin (IL)-1β. Additionally, melatonin was found to activate the nuclear factor erythroid 2-related factor signaling pathway, thereby safeguarding the mitochondrial function of AF cells from IL-1β, as evidenced by the increased level of adenosine triphosphate, mitochondrial membrane potential, and respiratory chain factor expression. The incorporation of melatonin into a self-healing hydrogel based on thiolated gelatin and β-cyclodextrin was proposed as a means of promoting AF regeneration. The successful implantation of melatonin-loaded hydrogel has been shown to facilitate in situ regeneration of AF tissue, thereby impeding IVD degeneration by preserving the hydration of nucleus pulposus in a rat box-cut IVD defect model. These findings offer compelling evidence that the development of a melatonin-loaded dynamic self-healing hydrogel can promote the mitochondrial functions of AF cells and represents a promising strategy for IVD regeneration.

Background Bone cement plays an important role in the treatment of osteoporotic vertebral compression fractures. Calcium phosphate cement (CPC) is a potential alternative to poly(methyl methacrylate), currently the gold standard of bone cements. However, the poor mechanical properties of CPCs limit their clinical applications. The objective of this study was to develop reinforced CPCs for minimally invasive orthopedic surgeries by compositing silk fibroin (SF) with α-tricalcium phosphate. Methods SF solution was treated with calcium hydroxide and characterized by Zeta potential analyzer and Fourier transform infrared spectroscopy. The alkaline-treated SF (tSF) was com-posited with α-tricalcium phosphate to obtain tSF/CPC composite, which was characterized using mechanical tests, scanning electron microscopy, handling property and biocompatibility tests, and sheep vertebral augmentation tests. Results Upon treatment with calcium hydroxide, larger SF particles and more abundant negative charge appeared in tSF solution. The tSF/CPCs exhibited a compact structure, which consisted of numerous SF -CPC clusters and needle-like hydroxyapatite (HAp) crystals. In addition, high transition rate of HAp in tSF/CPCs was achieved. As a result, the mechanical property of tSF/ CPC composite cements was enhanced remarkably, with the compressive strength reaching as high as 56.3±1.1 MPa. Moreover, the tSF/CPC cements showed good injectability, anti-washout property, and decent biocompatibility. The tSF/CPCs could be used to augment defected sheep vertebrae to restore their mechanical strength. Conclusion tSF/CPC may be a promising composite bone cement for minimally invasive orthopedic surgeries.

Degenerative disc disease (DDD) is a leading cause of low back pain, which severely affects the quality of life and incurs significant medical cost. Annulus fibrosus(AF) injuries can lead to substantial deterioration of intervertebral disc degeneration. However, the AF repair/regeneration remains a challenge due to the intrinsic cellular, biochemical and biomechanical heterogeneity of AF tissue. Tissue engineering would be a promising approach for AF regeneration. This article aims to provide a brief overview of the fundamental aspects of AF, the current achievements and future challenges of AF tissue engineering. A multidisciplinary approach is proposed for future studies to fully mimic the native AF tissue and its microenvironment, including choosing adequate cell source, preparing scaffolds with hierarchical microstructures, supplementing appropriate growth factors, and enforcing suitable mechanical stimulation. Hopefully, the engineered AF tissues would be effectively used to facilitate the treatment of DDD in the future.