High-density culturing of the dermal fibroblast cells on hydrogel-based soft microcarriers for cell therapy application

•Smart microcarriers were used for the high-density culture of human dermal fibroblasts.•The optimized microcarriers supported cell growth while maintaining cell phenotype.•Cells grown on microcarriers showed significant upregulation in collagen gene expression.•Cells grown on microcarriers showed significant in-vitro collagen production. Dermal fibroblasts play a pivotal role in cell therapy, serving as versatile cells essential for tissue repair and regeneration. Their unique ability to produce extracellular matrix components contributes significantly to the efficacy and success of various cell-based therapies in treating skin-related conditions and wounds. Scaling up the production of dermal fibroblasts poses a challenge due to their limited lifespan in culture and the need to maintain their specialized functions over multiple generations. Bioreactors offer a promising solution by providing controlled environments that optimize cell growth, allowing for higher yields of dermal fibroblasts while preserving their functionality and minimizing the limitations associated with traditional culture methods. To overcome the critical challenges in large-scale cell manufacturing, we fine-tuned the composition of our existing smart microcarrier, Cytogel, and tailored its chemical and physical properties to cultivate dermal fibroblasts. The fibroblast cell attachment rate to the new optimized formulation is more than 90%, followed by 60% thermal detachment efficiency in 1 h. Additionally, cells harvested from Cytogel displayed superior CD90 expression and enhanced collagen production compared to fibroblasts cultured in tissue flasks in both static and dynamic bioreactor cultures. Overall, our developed hydrogel-based microcarriers exhibited significant promise for efficient cell expansion, offering a groundbreaking approach for industrial-scale cell culture for cell therapeutic applications.