{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:43:50Z","timestamp":1790639030057,"version":"4.1.0"},"reference-count":258,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon Europe programme through a Marie Sk\u0142odowska-Curie Actions (MSCA) Postdoctoral Fellowship","award":["101207455"],"award-info":[{"award-number":["101207455"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Restoration of the osteochondral unit remains a major challenge in regenerative orthopaedics, largely due to the limited intrinsic healing capacity of articular cartilage and the complex, multilayered nature of the cartilage\u2013bone interface. Osteochondral regeneration must accommodate differences in cellular composition, vascularization, metabolic demand, and mechanical properties between cartilage and bone, while simultaneously recreating a stable, functional interface. While exogenous mesenchymal stem cell (MSC) therapies have dominated the field, their clinical translation has been hindered by donor variability, phenotypic instability, logistical complexity, and inconsistent long-term outcomes. Resident stem cells from sources such as articular cartilage, bone marrow, periosteum, synovium, synovial fluid, and adipose tissue (infrapatellar fat pad) can act as potential targets for in situ osteochondral regenerative therapies. Joint-resident MSCs are adapted to the biomechanical and biochemical environment of the joint and may therefore represent a promising cell source for osteochondral regeneration; however, much of the supporting evidence remains preclinical. Effective osteochondral repair depends on the precise orchestration of stem cell recruitment, maintenance of chondrogenic phenotypes, induction of osteogenic differentiation in the subchondral compartment, and modulation of local immune responses. Patient-specific factors, including age, inflammatory status, and the severity of osteoarthritis, can significantly influence the regenerative potential of resident MSC populations and should therefore guide biomaterial design strategies. The proposed niche-by-design framework integrates stem cell biology with advanced biomaterial engineering, offering a rational roadmap for developing next-generation therapies that promote endogenous osteochondral regeneration through targeted activation of joint-resident progenitor cells.<\/jats:p>","DOI":"10.3390\/cells15141290","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:47:32Z","timestamp":1784508452000},"page":"1290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Design Strategies to Target Joint Resident Mesenchymal Stem Cells for Osteochondral Regeneration"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1040-3746","authenticated-orcid":false,"given":"Khan","family":"Sharun","sequence":"first","affiliation":[{"name":"Regenerative Medicine Group, Department of Health Science and Technology, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7182-8169","authenticated-orcid":false,"given":"Shajahan Amitha","family":"Banu","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Group, Department of Health Science and Technology, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7143-4354","authenticated-orcid":false,"given":"Sathish","family":"Muthu","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Group, Department of Spine Surgery, Coimbatore 641045, India"},{"name":"Central Research Laboratory, Aarupadai Veedu Medical College and Hospital, Vinayaka Mission\u2019s Research Foundation, Puducherry 607403, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7716-1182","authenticated-orcid":false,"given":"Cristian Pablo","family":"Pennisi","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Group, Department of Health Science and Technology, Aalborg University, 9260 Gistrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41584-025-01222-z","article-title":"Stem and Progenitor Cells in the Synovial Joint as Targets for Regenerative Therapy","volume":"21","author":"Roelofs","year":"2025","journal-title":"Nat. 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