Elastomeric high‐mineral content hydrogel‐hydroxyapatite composites for orthopedic applications

Song, Jie; Xu, Jianwen; Filion, Tera M.; Saiz, Eduardo; Tomsia, Antoni P.; Lian, Jane B.; Stein, Gary S.; Ayers, David C.; Bertozzi, Carolyn R.

doi:10.1002/jbm.a.32110

Cited by 57 publications

(56 citation statements)

References 39 publications

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“…24,25 Although hydrogel-ceramic scaffolds have not been explored for calcified cartilage regeneration, this type of composite scaffold has been tested for bone applications and shown to promote calcification in vitro. 26,27 For example, in a study by Patel et al, nanosized HA particles were incorporated in a cyclic acetal hydrogel with predifferentiated rat bone marrow stromal cells. 28 It was found that HA presence increased cell alkaline phosphatase (ALP) activity and promoted osteogenesis.…”

Section: Introductionmentioning

confidence: 99%

A Hydrogel-Mineral Composite Scaffold for Osteochondral Interface Tissue Engineering

Khanarian

Jiang

Wan

et al. 2012

Tissue Engineering Part A

109

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Osteoarthritis is the leading cause of physical disability among Americans, and tissue engineered cartilage grafts have emerged as a promising treatment option for this debilitating condition. Currently, the formation of a stable interface between the cartilage graft and subchondral bone remains a significant challenge. This study evaluates the potential of a hybrid scaffold of hydroxyapatite (HA) and alginate hydrogel for the regeneration of the osteochondral interface. Specifically, the effects of HA on the response of chondrocytes were determined, focusing on changes in matrix production and mineralization, as well as scaffold mechanical properties over time. Additionally, the optimal chondrocyte population for interface tissue engineering was evaluated. It was observed that the HA phase of the composite scaffold promoted the formation of a proteoglycan-and type II collagen-rich matrix when seeded with deep zone chondrocytes. More importantly, the elevated biosynthesis translated into significant increases in both compressive and shear moduli relative to the mineral-free control. Presence of HA also promoted chondrocyte hypertrophy and type X collagen deposition. These results demonstrate that the hydrogel-calcium phosphate composite supported the formation of a calcified cartilage-like matrix and is a promising scaffold design for osteochondral interface tissue engineering.

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Section: Introductionmentioning

confidence: 99%

A Hydrogel-Mineral Composite Scaffold for Osteochondral Interface Tissue Engineering

Khanarian

Jiang

Wan

et al. 2012

Tissue Engineering Part A

109

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“…Toward this end, we developed FlexBone, a structural composite with up to 50 wt% nHA structurally integrated within a hydroxylated crosslinked carbon network. 2 Despite its high mineral content, this structural composite can withstand repetitive functional-compressive loads with excellent shape recovery under physiological conditions. 2 As a result of the high surface area of the nHA component and its intrinsic affinity for proteins and small molecule therapeutics, 3,4 FlexBone is also a suitable vehicle for delivering growth factors and antibiotics in a sustained and localized manner in vitro (Supplementary Fig.…”

mentioning

confidence: 99%

Elastomeric Osteoconductive Synthetic Scaffolds with Acquired Osteoinductivity Expedite the Repair of Critical Femoral Defects in Rats

Filion

Mason‐Savas

et al. 2011

Tissue Engineering Part A

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Regenerative medicine aspires to reduce reliance on or overcome limitations associated with donor tissuemediated repair. Structural bone allografts are commonly used in orthopedic surgery, with a high percentage of graft failure due to poor tissue integration. This problem is aggravated among elderly, those suffering from metabolic conditions, or those undergoing cancer therapies that compromise graft healing. Toward this end, we developed a synthetic graft named FlexBone, in which nanocrystalline hydroxyapatite (50 wt%) was structurally integrated with crosslinked poly(hydroxyethyl methacrylate) hydrogel, which provides dimensional stability and elasticity. It recapitulates the essential role of nanocrystalline hydroxyapatite in defining the osteoconductivity and biochemical microenvironment of bone because of its affinity for biomolecules. Here, we demonstrate that FlexBone effectively absorbed endogenously secreted signaling molecules associated with the inflammation/graft healing cascade upon being press-fit into a 5-mm rat femoral segmental defect. Further, when preabsorbed with a single dose of 400 ng recombinant human (rh) bone morphogenetic protein-2/7 heterodimer, it enabled the functional repair of the critical-sized defect by 8-12 weeks. FlexBone was stably encapsulated by the bridging bony callus and the FlexBone-callus interface was continuously remodeled. In summary, FlexBone combines the dimensional stability and osteoconductivity of structural bone allografts with desirable surgical compressibility and acquired osteoinductivity in an easy-to-fabricate and scalable synthetic biomaterial.

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“…ECM mimetic modifications and the provision of a nanocrystalline hydroxyapatite (nHAp)-rich micro-environment within synthetic hydrogels materials may be used to modulate specific cellular responses. 15 However, the development of an IPN biomaterial with both biological and synthetic components and ECM-mimetic modifications remains a significant challenge. A range of bioactive, inorganic nanoparticles such as nHAp, calcium phosphate, bioactive glasses and silica consist of minerals that are already present in the body, are necessary for the normal functioning of human bone tissue and have shown favourable biological responses.…”

Section: -10mentioning

confidence: 99%

Biomineralised interpenetrating network hydrogels for bone tissue engineering

Ingavle

Avadhanam

Zheng

et al. 2016

Bioinspired, Biomimetic and Nanobiomaterials

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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.

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Elastomeric high‐mineral content hydrogel‐hydroxyapatite composites for orthopedic applications

Cited by 57 publications

References 39 publications

A Hydrogel-Mineral Composite Scaffold for Osteochondral Interface Tissue Engineering

A Hydrogel-Mineral Composite Scaffold for Osteochondral Interface Tissue Engineering

Elastomeric Osteoconductive Synthetic Scaffolds with Acquired Osteoinductivity Expedite the Repair of Critical Femoral Defects in Rats

Biomineralised interpenetrating network hydrogels for bone tissue engineering

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