Key Takeaways & Executive Findings
- •• Biophysical cues such as substrate stiffness and fluid shear stress are pivotal in the pathogenesis of dental diseases like caries, periodontitis, and dentin hypersensitivity. • Exosomes derived from dental stem cells inherit biophysical signals and offer a promising cell-free therapy for dental regeneration, overcoming limitations of direct stem cell transplantation. • Biophysical cues regulate exosome biogenesis, release, and uptake, providing a mechanism to enhance their therapeutic efficacy in dental disease treatment. • This review highlights the potential of biophysical cue-regulated exosomes as novel targets for dental regenerative medicine, bridging mechanobiology and exosome-based therapy.
Abstract
Dental diseases such as caries and periodontitis have been common public health problems. Dental disease treatment can be achieved through stem cell-based dental regeneration. Biophysical cues determine the fate of stem cells and govern the success of dental regeneration. Some studies have manifested exosomes derived from stem cells could not only inherit biophysical signals in microenvironment but also evade some issues in the treatment with stem cells. Nowadays, biophysical cue-regulated exosomes become another promising therapy in dental regenerative medicine. However, methods to improve the efficacy of exosome therapy and the underlying mechanisms are still unresolved. In this review, the association between biophysical cues and dental diseases was summarized. We retrospected the role of exosomes regulated by biophysical cues in curing dental diseases and promoting dental regeneration. Our research also delved into the mechanisms by which biophysical cues control the biogenesis, release, and uptake of exosomes, as well as potential methods to enhance the effectiveness of exosomes. The aim of this review was to underscore the important place biophysical cue-regulated exosomes occupy in the realm of dentistry, and to explore novel targets for dental diseases.
1. Introduction
Dental diseases, such as dental caries, periodontitis, dentin hypersensitivity and even inflammatory root resorption during orthodontic treatment, represent vexing problems that have challenged public health worldwide [1–3]. These dental diseases influence not only the oral functions of patients but also their aesthetics, and have been observed to be tightly associated with various systemic diseases, such as cardiovascular diseases [4], diabetes mellitus [5], thyroid diseases [6], carcinogenesis [7], gastrointestinal diseases [8] and reproductive diseases [9].
Biophysical cues are recognized as pivotal features of dental diseases. For instance, substrate stiffness is crucial in dental caries and periodontitis development. Caries would diminish the mineralization degree and the stiffness of dentin [10]. An abrupt stiffness gradient in the periodontal ligament entheses is a hallmark of periodontitis [11]. As for dentin hypersensitivity, the fluid shear stress is the most influential biophysical cue. When the patient is chewing food, brushing teeth and breathing, dentinal fluid would flow through the dentinal tubules rapidly [12]. The fluid shear stress produced by dentinal fluid flow could activate the mechanotransduction in odontoblasts and induce toothache [13]. Besides, the inappropriate orthodontic force is the primary cause of inflammatory root resorption during orthodontic treatment [14, 15]. On the other hand, some biophysical therapies are mainstream therapies for dental diseases, currently. However, these methods, encompassing root canal therapy, filling restoration, scaling and root planing, fail to reinstate the biology functions of dental tissues.
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Bilun Jin, Yuxin Liao, Zhaojing Ding, Rui Zou, Feng Xu, Ye Li, Bo Cheng, Lin Niu (2026). The role of biophysical cues and their modulated exosomes in dental diseases: from mechanism to therapy. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-024-03990-z
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Frequently Asked Questions
What are biophysical cues in dental diseases?
Biophysical cues are physical signals from the microenvironment, such as substrate stiffness, fluid shear stress, and mechanical forces, that influence cell behavior. In dental diseases, these cues play a pivotal role in pathogenesis; for example, altered stiffness in dentin is associated with caries, and fluid shear stress triggers dentin hypersensitivity.
How do exosomes contribute to dental regeneration?
Exosomes derived from dental stem cells carry bioactive molecules and biophysical signals from their parent cells. They can modulate recipient cell behavior, promote tissue regeneration, and offer advantages over direct stem cell therapy, such as reduced immunogenicity and easier storage.
What is the significance of biophysical cue-regulated exosomes?
Biophysical cues can regulate the biogenesis, release, and uptake of exosomes, potentially enhancing their therapeutic efficacy. Understanding these mechanisms allows for the engineering of exosomes with improved regenerative properties for treating dental diseases.
What are the limitations of current dental disease treatments?
Current treatments like root canal therapy, filling restoration, and scaling fail to restore the biological functions of dental tissues. They primarily address symptoms rather than promoting true regeneration, highlighting the need for advanced regenerative approaches.
What is the future direction for dental regenerative medicine?
The future lies in leveraging biophysical cues to modulate exosome function, potentially creating targeted, cell-free therapies that can effectively regenerate dental tissues and treat diseases like caries and periodontitis.
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