Localized Growth Factor Delivery from Microparticles Modulates Osteogenic and Chondrogenic Gene Expression in a Growth Factor-dependent Manner in an ex vivo Chick Embryonic Bone Model

Growth factors play a crucial role in regulating various cellular functions, including proliferation and differentiation. Consequently, the biomaterial-based delivery of exogenous growth factors presents a promising strategy in regenerative medicine to manage the healing process and restore tissue function. For effective therapeutic applications, it is essential that these active compounds are precisely targeted to the site of regeneration, with release kinetics that align with the gradual pace of tissue growth. We have developed an ex vivo model utilizing a developing embryonic chick bone, and using PLGA-based microparticles as controlled-release systems, allowing for the investigation of the spatiotemporal effects of growth factor delivery on cell differentiation and tissue formation. Our findings demonstrate that BMP2 and FGF2 can significantly alter cell morphology and zonally pattern collagen deposition within the model, but only when the growth factor presentation rate is carefully regulated. Furthermore, the growth factor-dependent responses observed underscore the potential of this model to explore interactions between cells and the growth factors released from biomaterials in an approach which can be applied to bone tissue engineering. Statement of significance Current biomaterial-based strategies for bone tissue engineering face critical limitations in mimicking the spatial and temporal dynamics of native tissue development. This study introduces an innovative ex vivo embryonic chick bone model to evaluate localized, sustained growth factor delivery using PLGA microparticles. By precisely controlling the release of BMP2 and FGF2, the research demonstrates growth factor-specific modulation of osteogenic and chondrogenic gene expression and matrix deposition, outcomes that traditional in vitro models fail to capture. This physiologically relevant platform bridges a critical gap between basic in vitro assays and complex in vivo models, offering a powerful, low-cost tool for preclinical screening of regenerative therapies, and advancing the rational design of next-generation bone healing strategies.