sorenjoh

• Saiz, Augustine Mark; Jamous, Reem; Stötzel, Sabine; Rahmati, Maryam; Holmboe, Leonard Volrath & Johnson, Soren [Show all 16 contributors for this article] (2026). Limited Added Effect of Proline‐Rich P6 Peptide to Cross‐Linked Hyaluronic Acid After Partial Lateral Meniscectomy in Sheep. Smart Medicine. ISSN 2751-1863. 5(4). doi: 10.1002/smmd.70048. Full text in Research Archive Show summary

  This study evaluates whether a proline‐rich P6 peptide provides added benefit to a cross‐linked hyaluronic acid (HA) hydrogel after partial lateral meniscectomy‐associated osteoarthritis‐like change in sheep. The corrected four‐group framework includes Intact no‐surgery/no‐injection reference knees ( n  = 7) and 16 surgically injured knees from eight sheep assigned to Mnx (meniscectomy only, n  = 4), Mnx + HA ( n  = 6), or Mnx + HA + P6 ( n  = 6). Mnx + HA and Mnx + HA + P6 knees received intra‐articular injections at Weeks 0, 1, 2, and 4. Osteochondral tissues were evaluated at Week 12 by microCT, H&E scoring, and histochemical/immunohistochemical image analysis. Endpoint‐specific animal‐ or knee‐level models were used, with sheep identity included as a random effect when estimable. HA‐based treatment was associated with favorable trabecular microCT patterns after meniscectomy. However, the primary Mnx + HA + P6 versus Mnx + HA contrast was not significant for percent trabecular bone volume/BV/TV (+1.52 percentage points; 95% CI −2.22 to 5.26; p  = 0.427). Histology and IHC/histochemical findings showed selected exploratory tissue‐pattern signals, including collagen‐associated matrix staining, but did not establish consistent peptide‐specific superiority. These findings support cross‐linked HA as an intra‐articular biomaterial platform while defining requirements for confirmatory HA‐peptide hydrogel studies.

• Saiz, Augustine Mark; Rahmati, Maryam; Baldini, Tony Daniel; Bhat, Aneesh Satish; Johnson, Soren & Liu, Mengyao [Show all 15 contributors for this article] (2025). Mesenchymal stem cells delivered via a bioactive disordered peptide-hydrogel platform modulate early inflammation and enhance skeletal repair in a polytrauma model. Journal of Tissue Engineering. 16. doi: 10.1177/20417314251397106. Full text in Research Archive Show summary

  Over 30% of polytrauma patients with bone fractures suffer from impaired healing and nonunion due to persistent systemic inflammation. Existing biologic strategies for bone repair primarily focus on osteogenesis but are not designed to modulate systemic immune dysregulation, limiting their utility in the polytrauma setting. To overcome this, we developed a hyaluronic acid-based hydrogel (HA) incorporating osteogenic intrinsically disordered peptides (P2) and mesenchymal stem cells (MSCs) to promote bone regeneration and modulate inflammation simultaneously. MSCs entrapped in hydrogels containing P2 (HA + P2) exhibited increased cell viability, alkaline phosphatase activity, and calcium deposition under in vitro polytrauma conditions compared to MSCs in hydrogels alone (HA). We utilized a murine polytrauma model (4 mm femoral osteotomy + blunt chest trauma) in mice. We studied the inflammatory response and bone formation over 21 days in mice treated with (1) HA, (2) HA + P2, or (3) HA + P2 + MSCs. We observed that adding P2 enhanced bone mineralization at the fracture site, yet transplantation of MSCs with P2 further increased mineralization. Both HA + P2 and HA + P2 + MSCs groups attenuated the systemic inflammatory response to near healthy baseline values. The HA + P2 group significantly accelerated the first stages of fracture healing by upregulating genes encoding for collagen biosynthesis, modifying enzymes, and extracellular matrix (ECM)-receptor interaction. Mice treated with HA + P2 + MSCs exhibited transcriptional regulation resulting in the upregulation of key repair genes related to cell cycle control, E2F transcriptional regulation, and TP53-mediated DNA repair, alongside downregulation of inflammatory pathways (IL-2, IL-3, and IL-5 signaling) and improved fracture healing. This study demonstrated that the combination of intrinsically disordered peptides and mesenchymal stem cells in HA-based hydrogels enhances bone formation, modulates both local and systemic inflammation, and improves structural organization at the fracture site in polytrauma conditions.

• Saiz, Augustine Mark; Rahmati, Maryam; Johnson, Soren; Bhat, Aneesh Satish; Baldini, Tony Daniel & Øvrebø, Øystein [Show all 13 contributors for this article] (2025). Systemic versus local delivery of mesenchymal stem cells to improve the early stages of fracture healing in a polytrauma model. Journal of Biological Engineering. 19(1). doi: 10.1186/s13036-025-00554-4. Full text in Research Archive Show summary

  Fracture healing complications, including nonunion, are common in polytrauma patients partly due to systemic inflammatory dysregulation. Although mesenchymal stem cells (MSCs) have been widely explored for their regenerative properties, their therapeutic potential in polytrauma patients remains uncertain. Given the clinical interest in both systemic and localized stem cell therapies, understanding how delivery route influences MSCs biodistribution, inflammatory modulation, and therapeutic efficacy is critical for optimizing treatment strategies in polytrauma. Hence, we compared systemic versus local MSCs delivery in a polytrauma model. We evaluated inflammatory responses and bone formation in a C57BL/6J murine model across four groups: (1) isolated fracture, (2) polytrauma (femur fracture + chest trauma), (3) polytrauma + systemic MSC delivery, and (4) polytrauma + local MSC delivery in hyaluronic acid-based hydrogels at the fracture site. Polytrauma induced a prolonged inflammatory response characterized by elevated interleukin 1 alpha and beta (IL-1α & β), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and monocyte chemoattractant protein-1 and − 5 (MCP-1 & MCP-5). Both delivery methods significantly reduced inflammation and proinflammatory cytokines, though local delivery yielded more consistent effects. IVIS imaging confirmed MSC retention at the fracture site in the local delivery group, while systemic administration of MSCs resulted in pulmonary entrapment. Although systemic MSCs failed to enhance fracture healing significantly, local MSC delivery promoted bone formation evidenced by CT and histological characterizations. These findings demonstrate that local MSC delivery in a hydrogel scaffold represents a superior strategy for improving fracture healing in polytrauma patients compared to systemic delivery.

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