A functional agarose-hydroxyapatite scaffold for osteochondral interface regeneration

Abstract

Regeneration of the osteochondral interface is critical for integrative and functional cartilage repair. This study focuses on the design and optimization of a hydrogel-ceramic composite scaffold of agarose and hydroxyapatite (HA) for calcified cartilage formation. The first study objective was to compare the effects of HA on non-hypertrophic and hypertrophic chondrocytes cultured in the composite scaffold. Specifically, cell growth, biosynthesis, hypertrophy, and scaffold mechanical properties were evaluated. Next, the ceramic phase of the scaffold was optimized in terms of particle size (200 nm vs. 25 µm) and dose (0–6 w/v%). It was observed that while deep zone chondrocyte (DZC) biosynthesis and hypertrophy remained unaffected, hypertrophic chondrocytes measured higher matrix deposition and mineralization potential with the addition of HA. Most importantly, higher matrix content translated into significant increases in both compressive and shear mechanical properties. While cell hypertrophy was independent of ceramic size, matrix deposition was higher only with the addition of micron-sized ceramic particles. In addition, the highest matrix content, mechanical properties and mineralization potential were found in scaffolds with 3% micro-HA, which approximates both the mineral aggregate size and content of the native interface. These results demonstrate that the biomimetic hydrogel-ceramic composite is optimal for calcified cartilage formation and is a promising design strategy for osteochondral interface regeneration.

A biomimetic multi-layered collagen-based scaffold for osteochondral repair

“…The layered scaffold produced using the iterative layering technique described here has a porosity of >97%. This is marginally lower than the porosity of each of the constituent layers when fabricated as separate scaffolds, demonstrating that the process of layering and freeze-drying has minimal detrimental effect on the porosity 21 of the material. Homogenous cellular distribution throughout the entire construct was demonstrated in vitro (Fig.…”

“…Natural materials, including collagen [16,17] fibrin [18], hyaluronan [19], alginate [20] and agarose [21][22][23], have been widely investigated for use in osteochondral tissue repair.…”

Naturally derived biomaterials for development of composite bone scaffold: A review

“…Moreover the physical structure of the gels can be altered by varying the agarose concentration which results in desired pore sizes. Therefore agarose based hydrogel scaffolds [58] and composite scaffolds made of agarose combined with HAp [59] finds its applications in bone tissue engineering.…”

Enhanced Anchorage of Tissue-Engineered Cartilage Using an Osteoinductive Approach

“…However, other laboratories have attempted to augment the interfacial mechanical properties of engineered cartilage and subchondral bone using biomaterials such as chitosan particles [48], porous calcium polyphosphate [49], chitosan-chondroitin sulfate [50]. One group even used HA in conjunction with non-photopolymerizable alginate hydrogels and reported on its shear mechanical properties [18,51]. As data was reported as shear moduli [18], we first computed the shear moduli of our PEGDA-HA constructs at 14 and 28 days in the linear region of the mean stress-strain curve (n = 6 samples; curve not shown), which persisted up to ~ 5% strain.…”

“…A few research groups have been working on providing enhanced engineered cartilage to bone anchorage through the use of this bio active material [35,52]. One of the research group Lu et al [51], evaluated the potential of HA in alginate gel for regeneration of osteochondral interface and they were able to demonstrate successfully the formation of calcified cartilage like with the use of HA in their system. A summary of the different integration methods for engineered cartilage tissue constructs to bone, which were presented in this chapter, is described in Table 2.1: …”