Heo,Cheol Ho Yeo, Ki Baek Chae, Minjung Bak, Seon Young Choi, Hyeon Jin Jeong, Sohyeon Choi, Nakwon Kang, Seung-Kyun Jun, Sang Ho Ok, Myoung Ryul Kim, So Yeon 2025-04-08T09:00:41Z 2025-04-08T09:00:41Z 2025-04-04 2025-04 1742-7061 https://pubs.kist.re.kr/handle/201004/152185 Optimizing cell-matrix interactions for effective bone regeneration remains a significant hurdle in tissue engineering. This study presents a novel approach by developing a human mesenchymal stem cells (hMSCs)-embedded 3D aligned collagen for enhanced bone regeneration. A one-step mechanical strain was applied to a mixture of hMSCs and collagen, producing an hMSC-embedded, aligned 3D collagen hydrogel patch that mimics the natural bone matrix. Notably, the hMSCs embedded in the aligned collagen spontaneously differentiated into osteoblasts without external inducing reagents. Immunofluorescence analysis revealed that the BMP2-smad1/5 signaling pathway, critical for osteogenic differentiation, were activated by aligned collagen. In vivo experiments using a calvarial defect model confirmed that this approach effectively promotes new bone formation, starting centrally within the defect rather than from the edges adjacent to the existing bone. Our findings suggest that this simple method of pre-straining to create aligned 3D collagen embedded with hMSCs holds promise as a novel cell therapy platform for bone regeneration. English Elsevier BV Spontaneous bone regeneration achieved through one-step alignment of human mesenchymal stem cell-embedded collagen Article 10.1016/j.actbio.2025.03.007 1 Acta Biomaterialia, v.196, pp.136 - 151 Acta Biomaterialia 196 136 151 N scie scopus 001460932500001 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article IN-VITRO OSTEOGENIC DIFFERENTIATION PRE-OSTEOBLASTS BIOMATERIALS INTEGRIN FIBERS NANOFIBERS COMPOSITE SCAFFOLDS HYDROGELS Aligned 3D collagen Integrin Calvarial defect model Bone regeneration cell therapy Mesenchymal stem cells (MSC)