Patients- and tissue-specific bio-inks with photoactivated PRP and methacrylated gelatin for the fabrication of osteochondral constructs.

In osteochondral tissue engineering, while the biochemical and mechanical properties of hydrogels guide stem cell proliferation and differentiation, physical and chemical stimulators also affect the differentiation of stem cells. Herein, we presented a patient and tissue-specific strategy for the development of biomimetic osteochondral constructs with gradient compositions. Osteochondral constructs were fabricated by gradually printing of bio-inks consisting of therapeutic platelet-rich plasma (PRP), adipose tissue-derived mesenchymal stem cells (AdMSCs), and extracellular matrix (ECM) mimetic hydrogel, microwave-assisted methacrylated gelatin (Gel-MA). Periodic application of light in the near infrared region (600-1200 nm wavelength) was used to induce platelet activation and also AdMSCs' differentiation. Gel-MA has the same structure as type I collagen and PRP has cartilage tissue-specific bioactive components, so they provide the appropriate environment for the differentiation of AdMSCs to osteochondral tissue. Histology, immunocytochemistry, and biochemical analyses indicated enhanced glycosaminoglycan (GAG) and calcium content, mineralization, and ECM production. Furthermore, RT-PCR results indicated the expressions of bone- and cartilage-specific genes. In conclusion, the periodically photoactivated hydrogels with relatively low degradation rate and high mechanical strength, and tissue-specific biomimetic structure promoted in-vitro osteochondral tissue formation including hyaline and hypertrophic cartilage and bone phases.