Abstract
Articular cartilage has a very limited regeneration capacity. Therefore, injury or degeneration of articular cartilage results in an inferior mechanical stability, load-bearing capacity, and lubrication capability. Here, we developed a biomimetic scaffold consisting of macroporous polyvinyl alcohol (PVA) sponges as a platform material for the incorporation of cell-embedded photocrosslinkable poly(ethylene glycol) diacrylate (PEGDA), PEGDA-methacrylated chondroitin sulfate (PEGDA-MeCS; PCS), or PEGDA-methacrylated hyaluronic acid (PEGDA-MeHA; PHA) within its pores to improve in vitro chondrocyte functions and subsequent in vivo ectopic cartilage tissue formation. Our findings demonstrated that chondrocytes encapsulated in PCS or PHA and loaded into macroporous PVA hybrid scaffolds maintained their physiological phenotypes during in vitro culture, as shown by the upregulation of various chondrogenic genes. Further, the cell-secreted extracellular matrix (ECM) improved the mechanical properties of the PVA-PCS and PVA-PHA hybrid scaffolds by 83.30% and 73.76%, respectively, compared to their acellular counterparts. After subcutaneous transplantation in vivo, chondrocytes on both PVA-PCS and PVA-PHA hybrid scaffolds significantly promoted ectopic cartilage tissue formation, which was confirmed by detecting cells positively stained with Safranin-O and for type II collagen. Consequently, the mechanical properties of the hybrid scaffolds were biomimetically reinforced by 80.53% and 210.74%, respectively, compared to their acellular counterparts. By enabling the recapitulation of biomimetically relevant structural and functional properties of articular cartilage and the regulation of in vivo mechanical reinforcement mediated by cell–matrix interactions, this biomimetic material offers an opportunity to control the desired mechanical properties of cell-laden scaffolds for cartilage tissue regeneration.
Highlights
Owing to the biomechanical, biochemical, and structural properties of the native extracellular matrix (ECM) of articular cartilage and its dynamic regulation by specialized cells, i.e., chondrocytes, articular cartilage exhibits mechanical stability against friction and wear and provides a load-bearingPolymers 2017, 9, 655; doi:10.3390/polym9120655 www.mdpi.com/journal/polymersPolymers 2017, 9, 655 capability during joint movement [1,2]
By utilizing photopolymerizable cartilage-specific bioactive components, such as Methacrylated chondroitin sulfate (MeCS) and MeHA, for the encapsulation of primary rabbit chondrocytes within the pores of the polyvinyl alcohol (PVA) sponges, the functional properties of native cartilage were successfully recapitulated using both proteoglycans and chondrocytes
This could be achieved by slowly filling the internal pores of the PVA sponges with photopolymerizable poly(ethylene glycol) diacrylate (PEGDA)-MeCS (PCS), PEGDA-MeHA (PHA), or PEGDA containing isolated chondrocytes, followed by UV photopolymerization
Summary
Biochemical, and structural properties of the native extracellular matrix (ECM) of articular cartilage and its dynamic regulation by specialized cells, i.e., chondrocytes, articular cartilage exhibits mechanical stability against friction and wear and provides a load-bearingPolymers 2017, 9, 655; doi:10.3390/polym9120655 www.mdpi.com/journal/polymersPolymers 2017, 9, 655 capability during joint movement [1,2]. Due to its intrinsic avascular nature, articular cartilage has a limited regenerative and self-healing capacity, and, there has been a tremendous interest in the development of efficient tissue engineering-based strategies to treat cartilage defects, which include the use of stem cells, soluble growth factors, and scaffolds [3,4,5,6,7]. The therapeutic potential of stem cells and various soluble growth factors has been investigated extensively, but emerging evidence suggests that recapitulating the physicochemical cues for articular cartilage with natural and synthetic polymer-based biomimetic materials could play an significant role in cartilage tissue homeostasis and regeneration [8,9,10]. PVA possesses desirable properties such as biocompatibility, nondegradability, low protein absorption, and tunable mechanical properties, it does not efficiently support cell adhesion on its surface owing to the hydrophilic moieties provided by the hydroxyl group (–OH) on its backbone [15,16]
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