Abstract
A meta-analysis revealed no advantage of surgical over non-surgical treatments, emphasizing the need for non-invasive methods, particularly for prevalent osteoarticular diseases like knee osteoarthritis. To enhance therapeutic efficacy, we developed a plasma-infused gelatin methacryloyl (GelMA) biocarrier loaded with bone marrow-derived mesenchymal stromal cells (BMSCs). These constructs were evaluated in vitro for their properties and paracrine interactions in non-inflamed and inflamed environments. GelMA infused with platelet-rich plasma (PRP) and platelet-poor plasma (FFP) were compared. Pristine GelMA was used as a control. Both PRP and FFP enhanced the proliferation and viability of BMSCs in biocarriers, promoting cell survival pathways while inhibiting necrotic and apoptotic events. Proteomic analysis showed no differences in BMSC behavior between PRP and FFP in the absence of inflammation (p = 0.550). However, both plasmas significantly modified cell behavior under inflammatory conditions (p = 0.001). PRP- and FFP-infused biocarriers activated ten key signaling pathways, including HIF-1a, neuroinflammation, and extracellular matrix turnover. PRP-specific pathways included IL-17, IL-6, and several growth factor signaling pathways. No significant differences in angiogenesis were linked to platelet dose (p = 0.079), but both PRP and FFP significantly enhanced angiogenesis compared to GelMA alone (p < 0.001 for PRP, p = 0.002 for FFP). FFP showed stronger angiogenesis than PRP under IL-1&beta; treatment (p = 0.042). Plasma-infused biocarriers altered BMSC behavior in response to inflammatory cytokines compared to GelMA (p = 0.001). PRP specifically activated TGF-b signaling under IL-1b (Z=2.308, p-value 1.02E-35), which was not seen under TNF-a exposure. These findings suggest that PRP and FFP-infused biocarriers may offer promising improvements in regenerative therapies for inflammatory osteoarticular conditions like knee osteoarthritis.
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