In-situ bioprinting is attractive for directly depositing the therapy bioink at the defective organs to repair them, especially for occupations such as soldiers, athletes, and drivers who can be injured in emergency. However, traditional bioink displays obvious limitations in its complex operation environments. Here, we design a bioconcrete bioink with electrosprayed cell-laden microgels as the aggregate and gelatin methacryloyl (GelMA) precursor solution as the cement. Promising printability is guaranteed with a wide temperature range benefiting from robust rheological properties of photocrosslinked microgel aggregate and fluidity of GelMA cement. Composite components simultaneously self-adapt to biocompatibility and different tissue mechanical microenvironment. Strong binding on tissue-hydrogel interface is achieved by hydrogen bonds and friction when the cement is photocrosslinked. This bioink owns good portability and can be easily prepared in urgent accidents. Meanwhile, microgels can be cultured to mini tissues and then mixed as bioink aggregates, indicating our bioconcrete can be functionalized faster than normal bioinks. The cranial defects repair results verify the superiority of this bioink and its potential in clinical settings required in in-situ treatment.

Implantable hydrogel-based bioelectronics (IHB) can precisely monitor human health and diagnose diseases. However, achieving biodegradability, biocompatibility, and high conformality with soft tissues poses significant challenges for IHB. Gelatin is the most suitable candidate for IHB since it is a collagen hydrolysate and a substantial part of the extracellular matrix found naturally in most tissues. This study used 3D printing ultrafine fiber networks with metamaterial design to embed into ultra-low elastic modulus hydrogel to create a novel gelatin-based conductive film (GCF) with mechanical programmability. The regulation of GCF nearly covers soft tissue mechanics, an elastic modulus from 20 to 420 kPa, and a Poisson's ratio from − 0.25 to 0.52. The negative Poisson's ratio promotes conformality with soft tissues to improve the efficiency of biological interfaces. The GCF can monitor heartbeat signals and respiratory rate by determining cardiac deformation due to its high conformability. Notably, the gelatin characteristics of the biodegradable GCF enable the sensor to monitor and support tissue restoration. The GCF metamaterial design offers a unique idea for bioelectronics to develop implantable sensors that integrate monitoring and tissue repair and a customized method for endowing implanted sensors to be highly conformal with soft tissues.

Osteoclast precursors (OCPs) are thought to commit to osteoclast differentiation, which is accelerated by aging-related chronic inflammation, thereby leading to osteoporosis. However, whether the fate of OCPs can be reshaped to transition into other cell lineages is unknown. Here, we showed that M2 macrophage-derived extracellular vesicles (M2-EVs) could reprogram OCPs to downregulate osteoclast-specific gene expression and convert OCPs to M2 macrophage-like lineage cells, which reshaped the fate of OCPs by delivering the molecular metabolite glutamate. Upon delivery of glutamate, glutamine metabolism in OCPs was markedly enhanced, resulting in the increased production of α-ketoglutarate (αKG), which participates in Jmjd3-dependent epigenetic reprogramming, causing M2-like macrophage differentiation. Thus, we revealed a novel transformation of OCPs into M2-like macrophages via M2-EVs-initiated metabolic reprogramming and epigenetic modification. Our findings suggest that M2-EVs can reestablish the balance between osteoclasts and M2 macrophages, alleviate the symptoms of bone loss, and constitute a new approach for bone-targeted therapy to treat osteoporosis.

An imbalance in bone homeostasis results in bone loss and poor healing in bone diseases and trauma. Osteoimmune interactions, as a key contributor to bone homeostasis, depend on the crosstalk between mesenchymal stem cell-osteoblast (MSC-OB) and monocyte-macrophage (MC-Mφ) lineages. Currently, extracellular vesicles (EVs) are considered to be involved in cell-to-cell communication and represent a novel avenue to enhance our understanding of bone homeostasis and to develop novel diagnostic and therapeutic options. In this comprehensive review, we aim to present recent advances in the study of the effect of MC-Mφ-derived EVs on osteogenesis and the regulatory effects of MSC-OB-derived EVs on the differentiation, recruitment and efferocytosis of Mφ. Furthermore, we discuss the role of EVs as crucial mediators of the communication between these cell lineages involved in the development of common bone diseases, with a focus on osteoporosis, osteoarthritis, bone fracture, and periodontal disease. Together, this review focuses on the apparent discrepancies in current research findings and future directions for translating fundamental insights into clinically relevant EV-based therapies for improving bone health.