{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:27:43Z","timestamp":1786116463386,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Veterans Affairs, United States","award":["I01RX001991-01A2"],"award-info":[{"award-number":["I01RX001991-01A2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Funct. Biomater.","JFB"],"abstract":"<jats:p>In the contemporary era of minimally invasive surgery, injectable biomaterial scaffolds have demonstrated significant potential in bone tissue engineering (BTE). Completely injectable hydrogel substratum with microscale bone graft particulates delivered through a needle-shaped orifice shifts a new paradigm for surgical interventions in clinical settings. Despite growing interest in biopolymer-based BTE systems, clinically applicable delivery platforms and a mechanistic understanding of cell\u2013material interactions remain limited. This study developed a dual-syringe auto-mix system capable of generating an in situ cross-linking hydrogel\u2013mineral construct composed of gelatin\u2013hydroxyphenyl propionic acid, hyaluronic acid\u2013tyramine, horseradish peroxidase, hydrogen peroxide, and calcium phosphate particles of varying sizes. Material distribution, rheological and mechanical properties, and swelling were characterized. Goat bone marrow-derived mesenchymal stem cells served as the basis for examining how the composite affected cell viability, morphology, proliferation, contractility, osteogenic differentiation, mineralization, and chemotactic behavior. To determine whether these biological findings were supported mechanically, an ex vivo cone-beam computed tomography model was used to evaluate volumetric stability and resistance to deformation at the graft\u2013host interface. Cross-linking established a stable internal microarchitecture while remaining compatible with cell viability and nutrient-dependent survival. Formation of the gelatin\u2013hyaluronan (GH) network significantly increased the storage modulus relative to gelatin (G) alone, whereas subsequent calcium phosphate incorporation (GH-CP) preserved this mechanical competence while attenuating the volumetric expansion of GH. These physical characteristics were accompanied by more organized cell morphology, enhanced osteogenic differentiation, and mineral deposition throughout a larger portion of the matrix. Heterogeneous interpenetrating gap striation (HIGS) appeared in regions of cellular aggregation and matrix deposition, and a new conceptualization of the osteogenic phenomenon, termed cling osteogenesis, has been proposed. These outcomes support an intricate relationship between early mechanical stabilization, mechanotransduction, and osteogenesis in injectable hydrogel\u2013mineral systems.<\/jats:p>","DOI":"10.3390\/jfb17080389","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:46:38Z","timestamp":1786009598000},"page":"389","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanotransductive Osteogenesis Through Microarchitectural Stabilization in an Injectable Hydrogel\u2013Mineral System"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1984-206X","authenticated-orcid":false,"given":"Young K.","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Prosthodontics, Harvard School of Dental Medicine, Boston, MA 02115, USA"},{"name":"Tissue Engineering\/Regenerative Medicine, VA Boston Healthcare System, Boston, MA 02130, USA"},{"name":"Department of Prosthodontics, NYU College of Dentistry, New York, NY 10010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-583X","authenticated-orcid":false,"given":"Wanting","family":"Niu","sequence":"additional","affiliation":[{"name":"Tissue Engineering\/Regenerative Medicine, VA Boston Healthcare System, Boston, MA 02130, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Love","sequence":"additional","affiliation":[{"name":"Tissue Engineering\/Regenerative Medicine, VA Boston Healthcare System, Boston, MA 02130, USA"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3328-4858","authenticated-orcid":false,"given":"Myron","family":"Spector","sequence":"additional","affiliation":[{"name":"Tissue Engineering\/Regenerative Medicine, VA Boston Healthcare System, Boston, MA 02130, USA"},{"name":"Orthopedic Surgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1126\/science.1116995","article-title":"Tissue cells feel and respond to the stiffness of their substrate","volume":"310","author":"Discher","year":"2005","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.cell.2006.06.044","article-title":"Matrix elasticity directs stem cell lineage specification","volume":"126","author":"Engler","year":"2006","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nrm2594","article-title":"Mechanotransduction at a distance: Mechanically coupling the extracellular matrix with the nucleus","volume":"10","author":"Wang","year":"2009","journal-title":"Nat. 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