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These challenges are mostly attributed to the inadequacies of current methods, characterized by their high variability and the reliance on animal\u2010derived components, such as fetal bovine serum (FBS) in cell culture. To address these shortcomings, our approach diverges from conventional practices by prioritizing consistency and reproducibility, and the complete elimination of animal derivatives throughout the entire process. We have developed a novel method that utilizes a peptide\u2010functionalized photocrosslinkable methacrylated hyaluronic acid (MeHA\u2013RGD) hydrogel as a cell sealant for loading human adipose\u2010derived stem cells (hASCs) into a 3D porous polycaprolactone\u2013tricalcium phosphate (PCL\u2013TCP) scaffold. Additionally, we created a 3D\u2010printed vacuum\u2010assisted cell loading device to facilitate this process and ensure efficiency and consistency during cell loading. Our findings indicate that the MeHA\u2013RGD hydrogel supports both stem cell viability and osteogenic differentiation, demonstrating outcomes comparable to those achieved with fibrin glue, a conventional cell sealant widely used in BTE from autologous or xenogeneic sources, even under serum\u2010 and xeno\u2010free conditions. In the pursuit of clinical translation, it is vital that biomaterials exhibit low variability, are easily accessible, readily available, and completely free of animal derivatives. To our knowledge, this is the first study to employ a 3D\u2010printed vacuum\u2010assisted cell loading device system within a fully defined hybrid 3D system under complete serum\u2010 and xeno\u2010free conditions. These findings unravel and encourage alternative approaches in addressing the existing challenges in BTE, thereby facilitating and accelerating clinical translation in the future.<\/jats:p>","DOI":"10.1155\/term\/7287217","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T10:03:21Z","timestamp":1751537001000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fully Defined 3D Hybrid System for Bone Tissue Engineering: Integration of MeHA\u2013RGD\/PCL\u2013TCP Scaffolds With Human Stem Cells via 3D\u2010Printed Vacuum\u2010Assisted Cell Loading Device"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1741-2425","authenticated-orcid":false,"given":"Jolene","family":"Quek","sequence":"first","affiliation":[]},{"given":"Catarina","family":"Vizetto-Duarte","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7276-3563","authenticated-orcid":false,"given":"Kee Woei","family":"Ng","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5845-1731","authenticated-orcid":false,"given":"Swee Hin","family":"Teoh","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3348-9602","authenticated-orcid":false,"given":"Yen","family":"Choo","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10856-014-5240-2"},{"key":"e_1_2_10_2_2","unstructured":"DahiyaU. 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