Abstract
Cartilage injury is the main cause of disability in the United States, and it has been projected that cartilage injury caused by osteoarthritis will affect 30% of the entire United States population by the year 2030. In this study, we modified hyaluronic acid (HA) with γ-poly(glutamic) acid (γ-PGA), both of which are common biomaterials used in cartilage engineering, in an attempt to evaluate them for their potential in promoting cartilage regeneration. As seen from the results, γ-PGA-GMA and HA, with glycidyl methacrylate (GMA) as the photo-crosslinker, could be successfully fabricated while retaining the structural characteristics of γ-PGA and HA. In addition, the storage moduli and loss moduli of the hydrogels were consistent throughout the curing durations. However, it was noted that the modification enhanced the mechanical properties, the swelling equilibrium rate, and cellular proliferation, and significantly improved secretion of cartilage regeneration-related proteins such as glycosaminoglycan (GAG) and type II collagen (Col II). The cartilage tissue proof with Alcian blue further demonstrated that the modification of γ-PGA with HA exhibited suitability for cartilage tissue regeneration and displayed potential for future cartilage tissue engineering applications. This study built on the previous works involving HA and further showed that there are unlimited ways to modify various biomaterials in order to further bring cartilage tissue engineering to the next level.
Highlights
Prior to the Michael addition reaction, the γ-poly(glutamic) acid (γ-PGA) was first thiolated with different concentrations of hyaluronic acid (HA) so to as allow the subsequent reaction. γ-PGA is a bacterially produced, water-soluble polyamide currently widely used in tissue engineering due to its natural origin and biodegradability [22]
Increasing concentrations of HA were found to cause a decline in mechanical properties such as the tensile modulus, but this led to improvements in attaining swelling equilibrium in the hydrogels
Further studies showed that the HA2 groups exhibited significantly enhanced cellular proliferation and secretion of cartilage-regeneration-related proteins such as glycosaminoglycan (GAG) and collagen II (Col II) at all time points when compared to HA1 and HA0
Summary
The development of tissue engineering and 3D printing have made it possible to combine cell-based therapies with biomaterials, which have repeatedly been shown to enhance the formation of hyaline cartilage tissues with improved mechanical, physical, and biological characteristics as compared to previous fibrocartilaginous tissue [8,9,10,11]. In vivo and in vitro results have shown that modification with γ-PGA enhances the mechanical strength of hydrogels and increases the secretion of GAGs from chondrocytes. The initial results showed that the modified hydrogels had higher porosity and improved mechanical strength and degradation rates, as well as enhanced secretion of Col II and GAGs. To the best of our knowledge, there have been no reports in which γ-PGA and HA were combined and assessed for feasibility of use in cartilage tissue engineering. These results suggest that HA modification is suitable for future cartilage regeneration studies and applications
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