One of the most common craniofacial congenital deficiencies is cleft palate with an incidence of 1.7:1000 live births. The clinical management of cleft palate involves multiple surgical interventions and gives rise to post-operative complications. Recently, tissue-engineering approaches have been developed to treat cleft palate using osteoprogenitor (bone forming) cells seeded on biodegradable electrospun mat scaffolds to repair the defects. Animal sera are frequently employed as a regular supplement in vitro for osteoprogenitor cell proliferation and differentiation in culture conditions. However, serious drawbacks have been recorded, such as contamination, poorly defined components, and disease transmission. To overcome these obstacles, xeno-free media have recently been developed. This project aims to test a set of commercially available xeno-free media or supplements in which human-derived cells (hBMSCs and HJPs) can be grown to create a bone-like matrix suitable for craniofacial tissue engineering. The investigation showed that a commercially available medium containing 2% (v/v) human serum is best able to support human Bone Marrow Stem Cells (hBMSC) growth and differentiation among the media tested. However, there was noticeable donor variability in cell growth rates and osteogenic potential in the different media studied. Although 10% (v/v) foetal bovine serum is frequently employed for the proliferation of cells supporting in vitro growth, it was shown to poorly to support osteogenic differentiation compared to human-derived culture media. Polycaprolactone scaffolds were fabricated by electrospinning and these were shown support osteogenesis and bone-like matrix formation in selected xeno-free media with differential effects on secretion of angiogenic growth factor (VEGF). A tri-layer PCL mat scaffold could support and separate three different cell types (Fibroblasts, Keratinocytes, and hBMSCs) to allow osteogenic differentiation on one side and create an oral mucosa on the other side indicating this would be a promising scaffold to incorporate the cell types needed for cleft palate repair.