Chenglin Zhang,  Hongyang Zhao,  Zheng Zhang,  Yifan Gao,  Rui Gao^*,  Junyou Wang^*,  Xuhui Zhou^*

, 0(0): 00084. https://doi.org/10.12336/bmt.24.00084

Osteoarthritis (OA) is a degenerative joint disease marked by periarticular bony overgrowth and the degradation of articular cartilage, leading to severe pain, impaired joint function, and reduced quality of life for those affected. Current OA treatments, including pharmacotherapy, physical therapy, and joint replacement surgery, often provide limited therapeutic benefits and are associated with various side effects. As a result, there is a pressing need for alternative treatment options. Gene therapy has emerged as a promising approach for achieving longer-lasting benefits by repairing or modulating the molecular and cellular mechanisms within the joint. Specifically, gene therapy for OA involves either suppressing the expression of detrimental genes or enhancing the expression of therapeutic genes. The success of these approaches, however, significantly depends on the safe and efficient delivery platforms used. Given the risks of insertional mutations and high production costs associated with viral vectors, considerable efforts have been made to develop non-viral systems as safer and more cost-effective alternatives for gene delivery. Over the past few decades, a variety of innovative non-viral vectors with integrated functions have been proposed, successfully overcoming the challenges of gene delivery. The substantial progress made in the rational design of these vectors, along with their enhanced performance in OA gene therapy, warrants a comprehensive and timely review. This article aims to summarize these advancements, starting with a discussion of representative therapeutic gene targets for OA treatment. We then review the innovative non-viral vectors used in OA gene therapy, including lipids, extracellular vesicles, natural and synthetic polymers, inorganic nanoparticles, and protein/peptide carriers. Finally, we address key aspects that need further optimization to facilitate the design of non-viral vectors and promote their therapeutic application in OA treatment. 

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Hairu Sui,  Zhonglin Wu,  Ziqi Xiong,  Hui Zhang,  Boon Chin Heng,  Jing Zhou^*

, 0(0): 00087. https://doi.org/10.12336/bmt.24.00087

Skeletal injuries and disorders are major causes of physical disability worldwide, posing an intractable clinical challenge. Within the field of regenerative medicine, researchers are continuously developing new therapeutic strategies to promote bone regeneration. Small molecules, defined as bioactive compounds with a molecular weight of <1,000 Da, have emerged as promising agents capable of precisely regulating intracellular signaling pathways to enhance bone regeneration. Their cost-effectiveness, superior membrane permeability, and minimal immunogenicity have positioned them at the forefront of both fundamental research and clinical applications. In recent years, advancements in artificial intelligence have accelerated the development and screening of small-molecule drugs, broadening their potential therapeutic applications. Furthermore, innovations in dynamic drug delivery systems have advanced the concept of spatial precision, enabling the controlled release of drug doses over time and achieving the spatiotemporal application of small molecules. These systems release specific small molecules in a sequence, synchronizing therapeutic interventions with the dynamic process of bone healing. Spatiotemporal delivery strategies, which effectively replicate the complex and highly ordered processes of bone healing, have the potential to reduce drug side effects and enhance healing efficacy. However, clinical translation remains hindered by insufficient spatiotemporal control and limited pharmacokinetic precision, challenges that this review explores in depth. We systematically examine stage-specific molecular targets of signaling pathways and their corresponding small molecule modulators. In addition, we discuss current approaches to spatiotemporal delivery strategies, such as stimuli-responsive delivery systems. Finally, we explore the status of clinical applications, the challenges encountered, and potential solutions regarding the spatiotemporal release strategy. We hope this review will contribute to the development of future spatiotemporal delivery strategies, ultimately improving outcomes for patients with impaired fracture healing.

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Sofiya Eksharova,  Yuliya Poletaeva,  Anna Kurenkova,  Denis Mishchenko,  Egor Aydakov,  Vladimir Serdyukov^*

, 0(0): 00073. https://doi.org/10.12336/bmt.24.00073

The threat of bacterial growth on the skin under the prosthetic liners or sleeves is an important problem, which can cause various serious diseases up to the repeated amputation. One of the promising ways to solve this problem is to use antibacterial materials as a liner/ sleeve material. Among others composite based on the silicone polymer with silver particles additive is may be a simple and effective solution, since the silicone is the main material for the prosthetic liners and sleeves and silver demonstrates pronounced antibacterial effect. However, the questions related to the optimal concentration of silver in silicone that results in maximum antibacterial efficiency without harming human skin are still open. In the present work, synthesis of metallic silver powder from a mixture of micro- and nanoparticles was performed and composite samples based on silicone polymer with different silver concentrations were fabricated. The antibacterial properties of fabricated samples were studied using the microdilution method against gram-positive spore-forming bacteria Bacillus subtilis. The cytotoxic effect of the tested samples was evaluated on healthy human fibroblast cell (NAF1nor). Moreover, the effect of adding silver micro- and nanoparticles to silicone on its extensibility and hardness was studied. The results showed that the addition of silver has a noticeable effect on the antibacterial properties of silicone polymer reaching more than 50%. Furthermore, all tested silicone-silver composites were shown to be non-toxic. The presence of silver does not significantly affect the relative elongation of the samples. However, hardness increases with higher silver concentrations. In the final phase, prototypes of the silver-filled silicone prosthetic sleeve were fabricated for utilisation by the patient at the prosthetic-orthopaedic clinic. The testing of the prototype was successfully completed by the patient, thereby demonstrating practical functionality and suitability for clinical use.

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Xun Guo,  Xiaoting Wang,  Jianli Ren^*

2025, 6(1): 110–111. https://doi.org/10.12336/biomatertransl.2025.01.010

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Haoyang Du,  Jiaxin Liu,  Manjie Zhang^*

2025, 6(1): 106–109. https://doi.org/10.12336/biomatertransl.2025.01.009

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