The fabrication of biomimetic biphasic CAN-PAC hydrogel with a seamless interfacial layer applied in osteochondral defect repair

Abstract

Cartilage tissue engineering based on biomimetic scaffolds has become a rapidly developing strategy for repairing cartilage defects. In this study, a biphasic CAN-PAC hydrogel for osteochondral defect (OCD) regeneration was fabricated based on the density difference between the two layers via a thermally reactive, rapid cross-linking method. The upper hydrogel was cross-linked by CSMA and NIPAm, and the lower hydrogel was composed of PECDA, AAm and PEGDA. The interface between the two layers was first grafted by the physical cross-linking of calcium gluconate and alginate, followed by the chemical cross-linking of the carbon-carbon double bonds in the other components. The pore sizes of the upper and lower hydrogels were ~187.4 and ~112.6 μm, respectively. The moduli of the upper and lower hydrogels were ~0.065 and ~0.261 MPa. This prepared bilayer hydrogel exhibited the characteristics of mimetic composition, mimetic structure and mimetic stiffness, which provided a microenvironment for sustaining cell attachment and viability. Meanwhile, the biodegradability and biocompatibility of the CAN-PAC hydrogel were examined in vivo. Furthermore, an osteochondral defect model was developed in rabbits, and the bilayer hydrogels were implanted into the defect. The regenerated tissues in the bilayer hydrogel group exhibited new translucent cartilage and repaired subchondral bone, indicating that the hydrogel can enhance the repair of osteochondral defects.

Substrate stiffness regulated migration and angiogenesis potential of A549 cells and HUVECs

“…Exogenously delivered recombinant MMP‐7 was demonstrated to induce tumor angiogenesis through directly stimulating the proliferation of ECs (Nishizuka et al, ). However, the mechanism by which A549 cells on different substrate stiffness regulated the expressions of MMP3 and MMP7 in HUVECs was not clear, and it may be influenced by other cytokines or growth factors, which were not analyzed in this study (Liao et al, ). A549 cells secreted more MMPs on stiffer substrates, which not only can help degradation of ECM and pave ways for them to migrate and metastasize, but also can promote angiogenesis by promote the expressions of angiogenic growth factors in HUVECs.…”

Stiffness regulates the proliferation and osteogenic/odontogenic differentiation of human dental pulp stem cells via the WNT signalling pathway

“…It is important to study the factors—which many researchers have explored—that affect the biological behaviour of DPSCs. Moreover, there has been an increased focus on the design of scaffolds for dental pulp tissue regeneration or bone tissue engineering . However, the design of an overwhelming majority of these scaffolds was focused on the matrix architecture or composition to enhance odontogenic differentiation .…”

“…Moreover, there has been an increased focus on the design of scaffolds for dental pulp tissue regeneration or bone tissue engineering. 25,26 However, the design of an overwhelming majority of these scaffolds was focused on the matrix architecture or composition to enhance odontogenic differentiation. 27,28 It remains an unclear subject whether and how the stiffness of the substrates influences the odontogenic differentiation of DPSCs.…”

Regulating osteogenesis and adipogenesis in adipose‐derived stem cells by controlling underlying substrate stiffness

“…Polydimethylsiloxane (PDMS) matrices, serve as two‐dimensional culture formats, and can be cured using an organometallic crosslinking reaction. When different proportions of base oligomer and curing agent are used, the fully cross‐linked matrices produced display a wide range of stiffness, reflective of those found within natural tissues, including osteoid, cartilage, and adipose tissue (Fu et al, ; Liao et al, ; Shi et al, ). Given this flexibility, PDMS‐based matrices were used in this study.…”