Biomineralised interpenetrating network hydrogels for bone tissue engineering

Abstract

Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but their use is limited by inadequate mechanical strength and poor biocompatibility. In this study, to better mimic the mineral component and the mechanical strength of natural bone, two biocompatible materials, 2-hydroxyethyl agarose and poly (ethylene glycol) diacrylate, were combined with nanocrystalline hydroxyapatite (nHAp)-coated poly(lactic-co-glycolic acid) (PLGA) microspheres. A novel composite interpenetrating network (IPN) hydrogel scaffold was created to investigate its mechanical and osteoconductive performance for bone tissue engineering-related applications.The inclusion of nHAp-coated PLGA microspheres in an IPN hydrogel led to an increase in compressive modulus.In the absence of nHAp-coated microspheres, cell viability dropped to 59·1% at 3 weeks post-encapsulation.However, by incorporating nHAp-coated microspheres, cell viability improved to 80·6%. The capacity of composite IPN hydrogels to promote bone formation in cell culture was assessed. In the presence of mineralised microspheres, a composite IPN gel showed a significant increase in alkaline phosphatase activity and calcium (Ca) deposition following 3 weeks of incubation when compared with plain IPNs. This technology may be also applied to other cellbased applications where the improved mechanical integrity and osteoconductivity of cell-containing IPN hydrogels may be used to mimic bone tissue replacement.

Biomimetic bone-like composites as osteo-odonto-keratoprosthesis skirt substitutes

“…Previously, the authors explored agarose-PEGDA IPN hydrogels containing nHAp that exhibited cytocompatibility with the production of an ECM similar to bone matrix, which also has enhanced the mechanical properties of the IPN compared to the base networks. 62 Biological tissues with natural calcification such as bones and teeth contain mineral composition similar to HAp. Resorption studies on commercial bone substitutes and corals indicate that HAp alone is unstable and not appropriate as a KPro skirt material.…”

“…The double network IPN hydrogels developed in this study are particularly suited to replace the OOKP lamina since they are biocompatible, non-inflammatory, have tuneable porosity and mechanical strength, can support long-term cell survival, can be fabricated with the required morphology, have high stability and durability in the swollen state and for storage. The properties of this novel IPN skirt were assessed in our current and previous work in vitro , 62 in order to optimise these materials for dentine tooth substitution within the OOKP surgical procedure. Previously, the authors explored agarose-PEGDA IPN hydrogels containing nHAp that exhibited cytocompatibility with the production of an ECM similar to bone matrix, which also has enhanced the mechanical properties of the IPN compared to the base networks.…”

“…A hydrogel like PEGDA offers the advantage of bio-integration and tuneable implant strength and could address these issues. It has previously been shown that when used as a second network in IPN hydrogels, PEGDA helped significantly in boosting the mechanical performance relative to individual constituent networks while maintaining viability of encapsulated cells for bone 62 and cartilage [63][64][65][66] tissue engineering applications.…”

“… 67 – 70 nHAp was initially used as an osteo-conductivity enhancer for different materials by releasing ions required for bone formation due to its chemical interaction with bone forming cells and the native microenvironment 71 , 72 and thus providing nucleation sites for cell integration. 62 In previous study we explored the role of nHAp coated polymeric microspheres encapsulated in Interpenetrating network (IPN) hydrogel towards improving the mechanical integrity and osteo-conductive performance in bone tissue engineering-related applications. 62 We observed that, the inclusion of nHAp in an IPN hydrogel resulted in a substantial increase in mechanical strength, alkaline phosphatase activity and calcium deposition.…”

“… 62 In previous study we explored the role of nHAp coated polymeric microspheres encapsulated in Interpenetrating network (IPN) hydrogel towards improving the mechanical integrity and osteo-conductive performance in bone tissue engineering-related applications. 62 We observed that, the inclusion of nHAp in an IPN hydrogel resulted in a substantial increase in mechanical strength, alkaline phosphatase activity and calcium deposition. The current work adopts the strategy followed in our previous study and applies it to replacement of bone-dentine laminate during an OOKP procedure in the anterior eye that has not been tested yet.…”