Rare diseases, also known as orphan diseases, refer to a category of illnesses characterized by low prevalence, complex disease profiles, and severe symptoms. Rare diseases often manifest early in life, with symptoms frequently appearing in childhood. Among these conditions, changes in bone structure play a crucial role, and many rare diseases of this nature have a genetic basis and lack effective treatment modalities. With advances and breakthroughs in human gene research, the etiology of many rare diseases has been gradually uncovered. This paper reviews recent advances in gene therapy for rare pediatric bone diseases and its application in treating skeletal-related rare conditions. Special attention is directed towards cases such as osteogenesis imperfecta, X-linked hypophosphatemia and achondroplasia, and related gene therapy strategies are introduced. Osteogenesis imperfecta is primarily treated with bone marrow-derived mesenchymal stem cell transplantation and gene editing techniques, with experimental data validating their efficacy and safety; X-linked hypophosphatemic rickets has focused on FGF23 monoclonal antibodies, with clinical trials showing significant improvement in patient symptoms. Achondroplasia is primarily treated with small molecule tyrosine kinase inhibitors and C-type natriuretic peptide analogs, with research indicating these methods significantly improve bone growth. Although gene therapy research is still in its early stages, it provides hope for treating these rare diseases and may become a viable future treatment option for pediatric skeletal-related rare conditions.

BACKGROUND:Tissue engineering is considered an ideal treatment for growth plate regeneration.However,most of the current research on regenerative tissue engineering is the traditional scaffold-based strategy.As the limitations of traditional scaffolds are gradually revealed,the research direction is gradually diversifying. OBJECTIVE:To summarize the application of scaffold-based and scaffold-free strategies in the treatment of growth plate cartilage regeneration and their respective advantages and disadvantages. METHODS:The relevant articles were searched from PubMed,Wiley,and Elsevier.The search terms were"growth plate injury,regeneration,tissue engineering,scaffold,scaffold-free,biomimetic,cartilage"in English.The time was limited from 1990 to 2023.Finally,104 articles were included for review. RESULTS AND CONCLUSION:The biomimetic strategy is to reduce the cell composition,biological signals and unique mechanical properties of each region to the greatest extent by simulating the unique organizational structure of the growth plate,so as to build a biomimetic microenvironment that can promote tissue regeneration.Therefore,the design of a biomimetic scaffold is to simulate the original growth plate as far as possible in terms of composition,structure and mechanical properties.Although some results have been achieved,there is still the problem of the unstable regeneration effect.The scaffold-free strategy believes that the limitations of scaffolds will have adverse effects on regenerative therapy.Therefore,the design of scaffold-free constructs relies as much as possible on the ability of cells to generate and maintain extracellular matrix without interfering with cell-cell signals or introducing exogenous substances.However,there are some problems,such as poor stability,low mechanical strength and greater difficulty in operation.Biomimetic strategy and scaffold-free strategy have different emphases,advantages and disadvantages,but they both have positive effects on growth plate cartilage regeneration.Therefore,subsequent studies,whether adopting a biomimetic strategy or a scaffold-free strategy,will focus on the continuous optimization of existing technologies in order to achieve effective growth plate cartilage regeneration therapy.