{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:47:33Z","timestamp":1785415653932,"version":"3.56.0"},"reference-count":45,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Colorado Office of Economic Development & International Trade Global Business Development"},{"id":[{"id":"https:\/\/ror.org\/00fpx3104","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Mary Sue and Mike Shannon Network","award":["3036"],"award-info":[{"award-number":["3036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Bone marrow aspirate concentrate (BMAC) is widely used as a source of mesenchymal stromal\/stem cells (MSCs) for musculoskeletal regeneration; however, BMAC lacks essential bone marrow extracellular matrix (ECM) components, a critical component of the stem cell niche that regulates MSC survival, paracrine signaling, and regenerative capacity. We previously demonstrated that an ECM-retaining micronized bone marrow product (BMAX\u2122) preserves pro-regenerative MSC phenotypes in vitro. Human bone marrow from a single donor was processed into conventional BMAC or BMAX\u2122. Post-traumatic osteoarthritis was induced in immunodeficient rats using destabilization of the medial meniscus (DMM). Four weeks after surgery, animals were randomly assigned to receive intra-articular injections of BMAX\u2122, BMAC, or phosphate-buffered saline (n = 10\u201312 in each group). Pain-related behavior (n = 5\u20136\/group), histological assessment (n = 3\u20136\/group), and micro-computed tomography (n = 4\u20136\/group) were evaluated for up to 8 weeks after treatment. At 4 weeks after treatment, BMAC significantly increased the paw withdrawal threshold compared with PBS (p = 0.0068), whereas BMAX\u2122 significantly reduced knee joint swelling compared with both PBS (p = 0.0235) and BMAC (p = 0.0039), and BMAX\u2122 significantly improved knee bend scores compared with PBS (p = 0.0011). Neither treatment significantly improved OARSI histological scores at this time point. At 8 weeks after treatment, BMAX\u2122 significantly increased the paw withdrawal threshold compared with PBS (p = 0.0305), whereas BMAC showed a non-significant trend (p = 0.0517); both treatments significantly reduced knee bend scores compared with PBS (p = 0.0027 and p = 0.0255), and BMAX\u2122 demonstrated significantly lower knee bend scores than BMAC (p = 0.0090). BMAX\u2122 significantly reduced knee swelling compared with PBS (p = 0.0196). Histologically, BMAX\u2122 significantly improved OARSI scores in both the femoral condyle and tibial plateau compared with PBS (p = 0.0020 and p = 0.0003, respectively), whereas BMAC significantly improved only tibial plateau OARSI scores (p = 0.0014). Furthermore, BMAX\u2122 demonstrated significantly lower femoral condyle OARSI scores than BMAC (p = 0.0243). Micro-computed tomography revealed that both BMAX\u2122 and BMAC significantly reduced medial subchondral trabecular separation compared with PBS (p = 0.0340 and p = 0.0426, respectively), whereas no significant differences were observed between the two treatment groups for other bone structural parameters. In conclusion, preservation of the native bone marrow ECM was associated with improved functional outcomes and greater cartilage regeneration compared with conventional BMAC in this preclinical rat model of post-traumatic osteoarthritis. These findings support the concept that maintaining the native stem cell niche may enhance the therapeutic potential of bone marrow-derived cell therapies for osteoarthritis.<\/jats:p>","DOI":"10.3390\/cells15141249","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T11:43:34Z","timestamp":1783683814000},"page":"1249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical Evaluation of Human Donor-Derived Micronized Bone Marrow Stroma\/Parenchyma Versus Bone Marrow Aspirate Concentrate in a Rat Model of Post-Traumatic Knee Osteoarthritis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5070-1185","authenticated-orcid":false,"given":"Haruki","family":"Nishimura","sequence":"first","affiliation":[{"name":"The Steadman Philippon Research Institute, Vail, CO 81657, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuokui","family":"Xiao","sequence":"additional","affiliation":[{"name":"The Steadman Philippon Research Institute, Vail, CO 81657, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Singer","sequence":"additional","affiliation":[{"name":"The Steadman Philippon Research Institute, Vail, CO 81657, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5833-1548","authenticated-orcid":false,"given":"Xueqin","family":"Gao","sequence":"additional","affiliation":[{"name":"The Steadman Philippon Research Institute, Vail, CO 81657, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8496-1746","authenticated-orcid":false,"given":"William Sealy","family":"Hambright","sequence":"additional","affiliation":[{"name":"BMAX Medical LLC, Johnstown, CO 80534, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7516-4849","authenticated-orcid":false,"given":"Ryan","family":"Dregalla","sequence":"additional","affiliation":[{"name":"BMAX Medical LLC, Johnstown, CO 80534, USA"},{"name":"Colorado Spine Institute, Johnstown, CO 80534, USA"},{"name":"Elite Regenerative Stem Cell Specialists, Johnstown, CO 80534, USA"},{"name":"Dregalla Medical Technologies LLC, Fort Collins, CO 80525, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5611-8791","authenticated-orcid":false,"given":"Christopher T.","family":"Donner","sequence":"additional","affiliation":[{"name":"BMAX Medical LLC, Johnstown, CO 80534, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucanus S.","family":"Koldewyn","sequence":"additional","affiliation":[{"name":"BMAX Medical LLC, Johnstown, CO 80534, USA"},{"name":"Colorado Spine Institute, Johnstown, CO 80534, USA"},{"name":"Elite Regenerative Stem Cell Specialists, Johnstown, CO 80534, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9872-8758","authenticated-orcid":false,"given":"Edward Jeffrey","family":"Donner","sequence":"additional","affiliation":[{"name":"BMAX Medical LLC, Johnstown, CO 80534, USA"},{"name":"Colorado Spine Institute, Johnstown, CO 80534, USA"},{"name":"Elite Regenerative Stem Cell Specialists, Johnstown, CO 80534, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Huard","sequence":"additional","affiliation":[{"name":"The Steadman Philippon Research Institute, Vail, CO 81657, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.knee.2021.08.008","article-title":"The efficacy of intra-articular injections in the treatment of knee osteoarthritis: A network meta-analysis of randomized controlled trials","volume":"32","author":"Anil","year":"2021","journal-title":"Knee"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1007\/s00264-020-04703-w","article-title":"Bone marrow concentrate injections for the treatment of osteoarthritis: Evidence from preclinical findings to the clinical application","volume":"45","author":"Cavallo","year":"2021","journal-title":"Int. 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