Novel Microhydroxyapatite Particles in a Collagen Scaffold: A Bioactive Bone Void Filler?

Lyons, Frank; Gleeson, John P.; Partap, Sonia; Coghlan, Karen; O’Brien, Fergal J.

doi:10.1007/s11999-013-3438-0

Cited by 82 publications

(71 citation statements)

References 3 publications

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“…5–7 However, concerns remain about the resultant secondary wound site, supply and disease transmission, as well as the need for shaping of donor bone to fit often complex defects. With world demand topping two million bone replacement procedures per year, 8, 9 tissue engineering approaches offer the tantalizing possibility of generating a mechanically robust, patient-customized implant to enhance bone regeneration. However, the development of appropriate biomaterial substrates requires balancing structural, mechanical, and biomolecular design concerns as well as considering the appropriate selection of clinically-relevant cell populations.…”

Section: Introductionmentioning

confidence: 99%

“…9, 18–20 Such biomaterial substrates offer the advantages of tunability , namely allowing the manipulation of biomaterial morphology, such as fiber alignment; 21 topology, like surface roughness; 22 and substrate stiffness. 23, 24 However, the inclusion of growth factors such as BMP-2 or BMP-7 (known commercially as OP-1) 25, 26 or full-biochemical supplementation strategies such as osteogenic media 14, 27–29 remain a common, if not ubiquitous, practice of soluble supplementation.…”

Section: Introductionmentioning

confidence: 99%

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Mineralized collagen scaffolds induce hMSC osteogenesis and matrix remodeling

2015

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Biomaterials for bone tissue engineering must be able to instruct cell behavior in the presence of the complex biophysical and biomolecular environments encountered in vivo. While soluble supplementation strategies have been identified to enhance osteogenesis, they are subject to significant diffusive loss in vivo or the need for frequent re-addition in vitro. This investigation therefore explored whether biophysical and biochemical properties of a mineralized collagen-GAG scaffold were sufficient to enhance human mesenchymal stem cell (hMSC) osteogenic differentiation and matrix remodeling in the absence of supplementation. We examined hMSC metabolic health, osteogenic and matrix gene expression profiles, as well as matrix remodeling and mineral formation as a function of scaffold mineral content. We found that scaffold mineral content enhanced long term hMSC metabolic activity relative to non-mineralized scaffolds. While osteogenic supplementation or exogenous BMP-2 could enhance some markers of hMSC osteogenesis in the mineralized scaffold, we found the mineralized scaffold was itself sufficient to induce osteogenic gene expression, matrix remodeling, and mineral formation. Given significant potential for unintended consequences with the use of mixed media formulations and potential for diffusive loss in vivo, these findings will inform the design of instructive biomaterials for regenerative repair of critical-sized bone defects, as well as for applications where non-uniform responses are required, such as in biomaterials to address spatially-graded interfaces between orthopedic tissues.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mineralized collagen scaffolds induce hMSC osteogenesis and matrix remodeling

2015

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“…1, 35, 54 Carbodiimide crosslinking represent a common approach to tether biomolecules to a biomaterial surface, as well as to crosslinking collagen-based biomaterials. 22, 39, 55 In the context of crosslinking collagen-based scaffolds, previous efforts have examined the use of bulk versus step crosslinking, the impact of changing the EDC:NHS ratio, and the reaction pH.…”

Section: Discussionmentioning

confidence: 99%

Strategies to balance covalent and non-covalent biomolecule attachment within collagen-GAG biomaterials

et al. 2014

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Strategies to integrate instructive biomolecular signals into a biomaterial are becoming increasingly complex and bioinspired. While a large majority of reports still use repeated treatments with soluble factors, this approach can be prohibitively costly and difficult to translate in vivo for applications where spatial control over signal presentation is necessary. Recent efforts have explored the use of covalent immobilization of biomolecules to the biomaterial, via both bulk (ubiquitous) as well as spatially-selective light-based crosslinking, as a means to both enhance stability and bioactivity. However, little is known about how processing conditions during immobilization impact the degree of unintended non-covalent interactions, or fouling, that takes place between the biomaterial and the biomolecule of interest. Here we demonstrate the impact of processing conditions for bulk carbodiimide (EDC) and photolithography-based benzophenone (BP) crosslinking on specific attachment vs. fouling of a model protein (Concanavalin A, ConA) within collagen-glycosaminoglycan (CG) scaffolds. Collagen source significantly impacts the selectivity of biomolecule immobilization. EDC crosslinking intensity and ligand concentration significantly impacted selective immobilization. For benzophenone photoimmobilization we observed that increased UV exposure time leads to increased ConA immobilization. Immobilization efficiency for both EDC and BP strategies was maximal at physiological pH. Increasing ligand concentration during immobilization process led to enhanced immobilization for EDC chemistry, no impact on BP immobilization, but significant increases in non-specific fouling. Given recent efforts to covalently immobilize biomolecules to a biomaterial surface to enhance bioactivity, improved understanding of the impact of crosslinking conditions on selective attachment versus non-specific fouling will inform the design of instructive biomaterials for applications across tissue engineering.

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“…Good applied science draws a straight line from the laboratory to the practice of orthopaedic surgery, and so has some immediate clinical relevance. Recent examples in CORR 1 might include the studies by Elkins's group [2] and that of Lyons et al [4], although the latter emphasizes that drawing a sharp distinction between basic and applied research sometimes is difficult. By contrast, we are much less interested in studies whose answers can be predicted in advance based on wellestablished fundamental principles.…”

Section: F Rom the First Days Of Clinicalmentioning

confidence: 99%