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However, the realization of clinical potential of GPNMB in bone regeneration will require suitable delivery systems to overcome\u00a0challenges pertaining to poor dosing and poor retention at target sites. Distribution of osteogenic therapeutics away from the desired bone regeneration sites has been linked to serious adverse effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We developed thermoresponsive GPNMB-hydrogels using\u00a0PLA-b-PEG-b-PLA copolymer (10\u201330% w\/v) and demonstrated the ability to undergo solution-to-gel transition at physiologically relevant temperatures. The hydrogel formulations were characterized by vial inversion techniques, dynamic light scattering, rheological\u00a0assessments and bioretention studies. GPNMB loading (1\u201310\u00a0\u00b5g\/mL) did not interfere with hydrogel\u2019s thermo-reversibility and viscoelastic behaviors as obtained from rheological strain and frequency sweep tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>in-vitro<\/jats:italic>\n                      release of GPNMB reflected a\u00a0diffusion-controlled kinetic and is supported by hydrogel degradation pattern involving a rapid loss of the PEG units throughout the 8-week period and a delayed degradation of the PLA units.\n                      <jats:italic>In-vivo<\/jats:italic>\n                      long- and short-term safety studies, following GPNMB treatments,\u00a0showed acceptable serum levels of tissue function and inflammatory markers. There were no detectable signals of ectopic bone formation. Efficacy assessment of GPNMB-hydrogel was based on\n                      <jats:italic>in-vitro<\/jats:italic>\n                      osteoblast differentiation and\n                      <jats:italic>in-vivo<\/jats:italic>\n                      bone regeneration studies in\u00a0a murine calvaria defect model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The biofunctional properties of GPNMB-hydrogels were supported by enhancement of bone regeneration. Additional studies are warranted to fully examine the potential of GPNMB-hydrogel in bone regeneration using a\u00a0disease model of fracture healing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11095-025-03978-1","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T18:43:25Z","timestamp":1763491405000},"page":"2309-2327","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fabrication and Evaluation of Thermoresponsive GPNMB-Hydrogels as an Innovative Osteogenic Therapeutic Strategy"],"prefix":"10.1007","volume":"42","author":[{"given":"Tori","family":"Czech","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evin","family":"Hessel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenna","family":"Knowles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kalkedan T.","family":"Ameha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew A.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fayez F.","family":"Safadi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moses O.","family":"Oyewumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"issue":"10","key":"3978_CR1","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1038\/nm.2009","volume":"15","author":"JS Desgrosellier","year":"2009","unstructured":"Desgrosellier JS, Barnes LA, Shields DJ, Huang M, Lau SK, Prevost N, et al. 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