Yuting Shen,  Jiaying Xiong,  Yuchen Zhang,  Zhifei Gao,  Changhai Ding^*,  Yao Lu^*

, 0(0): 00011. https://doi.org/10.12336/bmt.25.00011

Bone and joint diseases, including bone fractures, osteoarthritis, and bone tumors, pose significant health challenges due to their debilitating effects on the musculoskeletal system. Conservative therapy and surgical treatment do not always achieve satisfactory outcomes in orthopedics, especially for degenerative bone and joint diseases. Messenger RNA (mRNA) therapy refers to the production of functional proteins and peptides by introducing mRNA into the body. The success of mRNA vaccines during the COVID-19 pandemic highlights the unique advantages of mRNA therapy, including biocompatibility, avoidance of genomic integration, and flexible, sustained delivery. These features make mRNA therapy a versatile therapeutic modality for the treatment of orthopedic diseases. In this review, we first provide an overview of the latest advances in mRNA therapy. We introduce structural modifications of mRNA and advanced gene-editing technologies, including modifications to nucleosides, mRNA domains, and codon sequences. We then discuss the development of mRNA delivery systems, such as nanomaterials, biomimetic carriers, and hydrogels, which enhance mRNA stability, reduce immunogenicity, and improve targeted delivery. This review also explores the application of mRNA therapy in orthopedic diseases, with a particular focus on its utilization in treating bone tumors and degenerative disorders. Despite promising developments, several challenges remain, including optimizing delivery efficiency, prolonging protein expression, and addressing tissue-specific barriers. Accordingly, the current limitations and future directions of mRNA therapy in orthopedic applications are emphasized. In conclusion, mRNA therapy holds great promise and may open new avenues for the treatment of orthopedic diseases and related fields.

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Yu Chen,  Zhiyong Chen,  Kewen Lei,  Jiandong Ding,  Lin Yu^*

2025, 6(2): 181–201. https://doi.org/10.12336/bmt.24.00052

The field of orthopaedic implants has experienced rapid growth in recent decades, evolving from a few obscure examples to become one of the most vibrant domains within regenerative medicine. Polyetheretherketone (PEEK) stands out as a formidable competitor in this field due to its exceptional biocompatibility and appropriate mechanical strength. However, the clinical application of PEEK is limited by its inherent biological inertness. Therefore, numerous studies have focused on overcoming the bio-inert issue of PEEK using surface activation techniques. It is necessary to delve into the intricate effects of these modifications and their corresponding methods. In this review, we provide a comprehensive summary of contemporary research on surface modification for enhancing osseointegration of PEEK implants, categorising them into four parts based on their modification methods and techniques used: (1) physical treatment, (2) wet chemical methods, (3) combination of physical and chemical treatments, and (4) bioactive coating. Finally, we outline the challenges and unmet needs that must be addressed by future designs of PEEK surfaces. Overall, altering the surface morphology and/or surface group of PEEK to obtain a rough, porous, hydrophilic, and bioactive surface, or incorporating bioactive agents/coatings with bone-forming abilities onto the surface of PEEK has shown great potential for promoting osseointegration, which can serve as a solid foundation for subsequent clinical translation.

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Yuanchao Zhu,  Junyu Su,  Tiantian Qi,  Geng Zhang,  Peng Liu,  Haotian Qin,  Qi Yang,  Sen Yao,  Yien Zheng,  Jian Weng^*,  Hui Zeng^*,  Fei Yu^*

2025, 6(2): 114–126. https://doi.org/10.12336/bmt.24.00038

Bones can fulfill functions in movement, attachment, and protection of internal organs. Bone diseases caused by ageing, trauma, infection, and other reasons may seriously affect the daily life of patients. Magnesium ions are closely associated with the maintenance of bone health. Integrating magnesium ions into delivery systems and hydrogels can improve their application, thus directly acting on the osteoblast cell lineage and influencing the proliferation and differentiation of relevant cells. The slow release of magnesium ions allows for their effects on the target site for a long time, reducing the clearance of magnesium ions in the body, which significantly contributes to bone repair. Magnesium-based bioalloy scaffolds have received widespread attention for their favourable biocompatibility, degradability, and bone-forming properties and play an important role in bone regeneration and repair. This article presents a review on the role and mechanism of magnesium-containing materials in bone repair and regeneration. By discussing the current challenges and future directions for magnesium-containing biomaterials, new insights are provided into the development of these materials in the field of orthopaedics. In conclusion, magnesium-containing biomaterials have great application value in orthopaedics.

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Hanlai Li,  Tingting Gu,  Jingjing Xu,  Lin Gan,  Chang Liu,  Jixian Wan,  Zhihao Mu,  Haiyan Lyu,  Zhibin Wang,  Qianqian Liu,  Jie Chen,  Yaohui Tang^*

2025, 6(2): 165–180. https://doi.org/10.12336/bmt.24.00020

Due to the limited effects of current treatments on brain repair and regeneration, stroke continues to be the predominant cause of death and long-term disability on a global scale. In recent years, hydrogel-based biomaterials combined with stem cells and extracellular vesicles have emerged as promising new treatments to improve brain regeneration after stroke. However, the clinical translation of hydrogel-based biomaterials for the treatment of brain injury is still far from satisfactory. In this review, we first summarise the present status of stroke-related clinical treatments and the advantages provided by hydrogel-based materials in combination with stem cells and extracellular vesicles in preclinical studies. We then focus on the possible causes of the gap between preclinical studies and clinical translation of hydrogel-based biomaterials from the perspective of biocompatibility and safety, the choices of preclinical models, the lack of clinical noninvasive imaging methods, standardisation and quality control, manufacturing scalability, and regulatory compliance. With the progress in the abovementioned areas, we believe that the clinical translation of hydrogel-based biomaterials will greatly improve brain regeneration after stroke and that this improvement will be realised by the general public in the near future.

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Juxin Pei,  Qinchao Zhu,  Yang Zhu,  Chengchen Guo,  Teresa G. Valencak,  Shi-Yang Tang,  Tanchen Ren^*,  Daxi Ren^*

2025, 6(2): 127–150. https://doi.org/10.12336/bmt.24.00071

Hydrogels are an advanced class of biomaterials with similar properties to living tissues. Several polymers have been investigated for the preparation of hydrogels that closely mimic the structural and functional properties of the extracellular matrix. Proteins with easily modifiable functional groups, specific biochemical effects, and sensitivity to external stimuli are promising candidates for the preparation of hydrogels for biomedical applications. Among them, natural milk proteins, due to their high yield, high-quality control, low cost, and certain biological properties, have become a major focus of research. However, there is a lack of comprehensive reviews focusing specifically on milk protein-based hydrogels. Here, we synthesise the developments in milk protein-based hydrogels, focusing primarily on hydrogels derived from milk proteins. We described the methods used to construct milk protein-based hydrogels and summarised advances in representative applications of milk protein-based hydrogels, such as controlled delivery and regenerative medicine, as well as related preclinical animal experiments and an exploratory clinical pilot study. Finally, we discuss the prospects of milk protein-based hydrogels in biomedical applications. We anticipate that this review will serve as a theoretical basis for the biomedical use of milk proteins and provide a reference for their continued development.

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