Event

Craniofacial bone defects, resulting from congenital abnormalities, disease, tumor resection, and traumatic injury, can result in severe implications for patient health and substantial healthcare costs. Traditional clinical techniques for bone defect repair include the implantation of autografts. While these approaches provide functional bone regeneration outcomes, donor site morbidity, lack of availability, long treatment courses, and considerable medical costs have necessitated the generation of novel therapeutic approaches. Tissue engineering (TE) strategies aim to produce functional bone tissue replacements through the combination of scaffolds, cells, and bioactive signals. While researchers have developed a wealth of bone tissue engineering (BTE) strategies over the last several decades, few have acknowledged the role of the periosteum in bone healing. The periosteum is a 100 µm thick sheath surrounding almost all bone tissue, consisting of an inner cambium layer, containing osteoprogenitor cell sources, and an outer fibrous layer, containing a dense collagen matrix, neural, and vascular networks. Periosteum plays a critical role in bone healing by providing both osteoprogenitor cells and local vasculature that infiltrate the defect site and orchestrate osteogenesis and neovascularization. Previous research in periosteum TE has utilized cell sheet engineering, electrospinning, or casting methods to produce either one or both layers of the periosteum, and these sheets are typically wrapped around allografts or osteogenic scaffolds and applied to long bone applications. While these studies have presented favorable outcomes in terms of bone regeneration and neovascularization, the lack of biomimetic design can limit their regenerative potential. Therefore, we hope to address these issues of biomimetic design through this work. First, we have developed a 4D bioprinting strategy to reduce extrusion bioprinting resolution below 100 µm to produce multi-layered thin membranous tissues (TMT), like the periosteum, in conjunction with their macroscale tissue counterparts, like bone. This allows for cell-cell population distances within the construct to be accurately controlled, which has been shown to impact paracrine signaling and cellular crosstalk. Additionally, we have investigated the impact of cell population heterogeneity and patterning within the cambium layer and determined its effects on paracrine signaling and subsequent osteogenic differentiation. The completion of these studies aids in achieving our long-term goal, which is the development of a bone-periosteal construct capable of inducing osteogenesis in vivo.