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International Journal of Bioprinting                            Bioprinted plasma biocarriers for MSC delivery






































            Figure 8. Predicted TGF-β1 network in platelet-rich plasma (PRP)-infused biocarriers. Lines depict molecular relationships, with details provided in the
            legend on the right. These lines indicate interactions where molecules bind or act upon one another. All molecular relationships are derived from scientific
            data in the IPA® knowledgebase.




            430 proteins in the conditioned media obtained from the   It is reported that GelMA serves as a scaffold for MSC
            biocarrier cultured in vitro for 96 h, and we also applied   adhesion and functions, while also acting as a biodegradable
            bioinformatics to predict the activation of canonical   and immune-compatible vehicle for delivering cytokines
            pathways. Similarly, approaches using proteomic studies   and GFs. 35,39  These biocarriers enhance the bioactivity
            have helped characterize complex molecular matrices,  and   and therapeutic potential of encapsulated cells, promoting
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            the integration of bioinformatics has helped in predicting   tissue regeneration and repair across various biomedical
            adipose derived mesenchymal stem cell (Ad-MSC)     applications. 25,27  Other researchers have demonstrated the
            performance in the presence of PRP molecules, resulting in   proof-of-concept by implanting GelMA/adipose stromal
            enhanced exosome secretion and upregulation of multiple   cell (ASC)/PRP into osteochondral defects in the patellar
            proteins involved in tissue repair and immune regulation. 10  groove of rabbits’ joints, resulting in higher histological,
                                                               macroscopic, and mechanical scores, highlighting the
               As previously reported, plasma-infused GelMA is                               39
            suitable for cell viability, survival, and supporting cell   synergistic effects of this combination.
            functions. 34–36  We demonstrated that PRP-infused GelMA   However, untangling the intricacies of tissue repair,
            provides optimal 3D conditions for BMSC proliferation,   which involves a myriad of molecules and multicellular
            thus less cell density is required for optimal delivery, e.g.,   cross-talks,  demands  advanced  technologies  to  identify
            cell density is commonly 1 × 10  cells/mL  versus 3 ×   driver molecules, and establish plausible hypotheses. Our
                                       7
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            10  cells/mL, thereby reducing the time of 2D expansion   proteomic analysis of plasma biomaterials revealed two
              6
            prior to bioprinting. Other studies have reported the   interconnected groups of proteins with significant roles in
            advantages of 3D-GelMA for induced pluripotent stem   regenerative medicine. Given the higher expression levels
            cell (iPSC)-derived MSC proliferation when bioreactors   of these molecules in PRP compared to FFP, we chose to
                              37
            are used concurrently.  Compared to monolayer cultures,   dope the hydrogel with both blood derivatives to explore
            3D conditions and biomechanical stimulation can enhance   the primary functions of PRP. The first group comprised
            MSC functionality. 38                              GFs  and neurotrophins, while  the second, less-studied

            Volume 10 Issue 6 (2024)                       312                                doi: 10.36922/ijb.4426
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