Osteoarthritis (OA) is the most prevalent degenerative joint disorder, affecting hundreds of millions of people globally. Current clinical approaches are confined to providing only symptomatic relief. Research over the past two decades has established that OA is not merely a process of wear and tear of the articular cartilage but involves abnormal remodelling of all joint tissues. Although many new mechanisms of disease have been identified in the past several decades, the efficient and sustainable delivery of drugs targeting these mechanisms in joint tissues remains a major challenge. Nanoparticles recently emerged as favoured delivery vehicles in OA treatment, offering extended drug retention, enhanced drug targeting, and improved drug stability and solubility. In this review, we consider OA as a disease affecting the entire joint and initially explore the pathophysiology of OA across multiple joint tissues, including the articular cartilage, synovium, fat pad, bone, and meniscus. We then classify nanoparticles based on their composition and structure, such as lipids, polymers, inorganic materials, peptides/proteins, and extracellular vesicles. We summarise the recent advances in their use for treatment and diagnosis of OA. Finally, we discuss the current challenges and future directions in this field. In conclusion, nanoparticle-based nanosystems are promising carriers that advance OA treatment and diagnosis.

Decellularised extracellular matrix (dECM) is a biomaterial derived from natural tissues that has attracted considerable attention from tissue engineering researchers due to its exceptional biocompatibility and malleability attributes. These advantageous properties often facilitate natural cell infiltration and tissue reconstruction for regenerative medicine. Due to their excellent fluidity, the injectable hydrogels can be administered in a liquid state and subsequently formed into a gel state in vivo, stabilising the target area and serving in a variety of ways, such as support, repair, and drug release functions. Thus, dECM-based injectable hydrogels have broad prospects for application in complex organ structures and various tissue injury models. This review focuses on exploring research advances in dECM-based injectable hydrogels, primarily focusing on the applications and prospects of dECM hydrogels in tissue engineering. Initially, the recent developments of the dECM-based injectable hydrogels are explained, summarising the different preparation methods with the evaluation of injectable hydrogel properties. Furthermore, some specific examples of the applicability of dECM-based injectable hydrogels are presented. Finally, we summarise the article with interesting prospects and challenges of dECM-based injectable hydrogels, providing insights into the development of these composites in tissue engineering and regenerative medicine.

Exosomes, a specialised type of extracellular vesicle, have attracted significant attention in the realm of tendon/ligament repair as a potential biologic therapeutic tool. While the competence of key substances responsible for the delivery function was gradually elucidated, series of shortcomings exemplified by the limited stability still need to be improved. Therefore, how to take maximum advantage of the biological characteristics of exosomes is of great importance. Recently, the comprehensive exploration and application of biomedical engineering has improved the availability of exosomes and revealed the future direction of exosomes combined with biomaterials. This review delves into the present application of biomaterials such as nanomaterials, hydrogels, and electrospun scaffolds, serving as the carriers of exosomes in tendon/ligament repair. By pinpointing and exploring their strengths and limitations, it offers valuable insights, paving the way the future direction of biomaterials in the application of exosomes in tendon/ligament repair in this field.

Understanding the in vivo transport process provides guidelines for designing ideal nanoparticles (NPs) with higher efficacy and fewer off-target effects. Many factors, such as particle size, morphology, surface potential, structural stability, and etc., may influence the delivering process of NPs due to the existence of various physiological barriers within the body. Herein, we summarise the distinct influences of NP physicochemical properties on the four consecutive in vivo transport steps: (1) navigating with bloodstream within blood vessels, (2) transport across vasculature walls into tumour tissues, (3) intratumoural transport through the interstitial space, and (4) cellular uptake & intracellular delivery by cancerous cells. We found that the philosophy behind the current consensus for NP design has certain similarities to the “Yin-Yang” theory in traditional Chinese culture. Almost all physicochemical properties, regardless of big or small sizes, long or short length, positive or negative zeta potentials, are double-edged swords. The balance of potential benefits and side effects, drug selectivity and accessibility should be fully considered when optimising particle design, similar to the “Yin-Yang harmony”. This paper presents a comprehensive review of the advancements in NPs research, focusing on their distinct features in tumour targeting, drug delivery, and cell uptake. Additionally, it deliberates on future developmental trends and potential obstacles, thereby aiming to uncover the ways these characteristics influence the NPs’ biological activity and provide theoretical guidance for the targeted delivery of NPs.

Peripheral nerve injury poses a great threat to neurosurgery and limits the regenerative potential of sacral nerves in the neurogenic bladder. It remains unknown whether electrical stimulation can facilitate sacral nerve regeneration in addition to modulate bladder function. The objective of this study was to utilise electrical stimulation in sacra nerve crush injury with newly constructed electroconductive scaffold and explore the role of macrophages in electrical stimulation with crushed nerves. As a result, we generated a polypyrrole-coated polycaprolactone/silk fibroin scaffold through which we applied electrical stimulation. The electrical stimulation boosted nerve regeneration and polarised the macrophages towards the M2 phenotype. An in vitro test using bone marrow derived macrophages revealed that the pro-regenerative polarisation of M2 were significantly enhanced by electrical stimulation. Bioinformatics analysis showed that the expression of signal transducer and activator of transcriptions (STATs) was differentially regulated in a way that promoted M2-related genes expression. Our work indicated the feasibility of electricals stimulation used for sacral nerve regeneration and provided a firm demonstration of a pivotal role which macrophages played in electrical stimulation.

Inflammation and angiogenesis, the major pathological changes of osteoarthritis (OA), are closely associated with joint pain; however, pertinent signalling interactions within subchondral bone of osteoarthritic joints and potential contribution to the peripheral origin of OA pain remain to be elucidated. Herein we developed a unilateral anterior crossbite mouse model with osteoarthritic changes in the temporomandibular joint. Microarray-based transcriptome analysis, besides quantitative real-time polymerase chain reaction, was performed to identify differentially expressed genes (DEGs). Overall, 182 DEGs (fold change ≥ 2, P < 0.05) were identified between the control and unilateral anterior crossbite groups: 168 were upregulated and 14 were downregulated. On subjecting significant DEGs to enrichment analyses, inflammation and angiogenesis were identified as the most affected. Inflammation-related DEGs were mainly enriched in T cell activation and differentiation and in the mammalian target of rapamycin/nuclear factor-κB/tumour necrosis factor signalling. Furthermore, angiogenesis-related DEGs were mainly enriched in the Gene Ontology terms angiogenesis regulation and vasculature development and in the KEGG pathways of phosphoinositide 3-kinase-protein kinase B/vascular endothelial growth factor/hypoxia-inducible factor 1 signalling. Protein-protein interaction analysis revealed a close interaction between inflammation- and angiogenesis-related DEGs, suggesting that phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (Pi3kcd), cathelicidin antimicrobial peptide (Camp), C-X-C motif chemokine receptor 4 (Cxcr4), and MYB proto-oncogene transcription factor (Myb) play a central role in their interaction. To summarize, our findings reveal that in subchondral bone of osteoarthritic joints, signal interaction is interrelated between inflammation and angiogenesis and associated with the peripheral origin of OA pain; moreover, our data highlight potential targets for the inhibition of OA pain.

Hydroxyapatite (HAP) porous microspheres with very high specific surface area and drug loading capacity, as well as excellent biocompatibility, have been widely used in tumour therapy. Mg²⁺ is considered to be a key factor in bone regeneration, acting as an active agent to stimulate bone and cartilage formation, and is effective in accelerating cell migration and promoting angiogenesis, which is essential for bone tissue repair, anti-cancer, and anti-infection. In this study, abalone shells from a variety of sources were used as raw materials, and Mg²⁺-doped abalone shell-derived mesoporous HAP microspheres (Mg-HAP) were prepared by hydrothermal synthesis as Mg²⁺/icariin smart dual delivery system (ICA-Mg-HAP, IMHA). With increasing of Mg²⁺ doping, the surface morphology of HAP microspheres varied from collapsed macroporous to mesoporous to smooth and non-porous, which may be due to Mg²⁺ substitution or coordination in the HAP lattice. At 30% Mg²⁺ doping, the Mg-HAP microspheres showed a more homogeneous mesoporous morphology with a high specific surface area (186.06 m²/g). The IMHA microspheres showed high drug loading (7.69%) and encapsulation rate (83.29%), sustained Mg²⁺ release for more than 27 days, sustained and stable release of icariin for 60 hours, and good responsiveness to pH (pH 6.4 > pH 5.6). In addition, the IMHA delivery system stimulated the rapid proliferation of bone marrow mesenchymal stem cells and induced apoptosis in MG63 cells by blocking the G2 phase cycle of osteosarcoma cells and stimulating the high expression of apoptotic genes (Bcl-2, caspase-3, -8, -9). This suggests that the abalone shell-based IMHA may have potential applications in drug delivery and tumour therapy.