The impact of discrete compartments of a multi-compartment collagen–GAG scaffold on overall construct biophysical properties

Weisgerber, Daniel W.; Kelkhoff, D. O.; Caliari, Steven R.; Harley, Brendan A.C.

doi:10.1016/j.jmbbm.2013.07.016

Cited by 45 publications

(55 citation statements)

References 46 publications

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“…The suspensions were maintained at this temperature for 2 h to completely freeze the suspension followed by sublimation of the ice crystals at 0°C and 200 mTorr to produce dry scaffolds with pores > 150 mm. 18,23 Scaffold crosslinking and hydration CG scaffolds were dehydrothermally crosslinked at 105°C for 24 h under vacuum (<25 torr) in a vacuum oven (Welch, Niles, IL) following lyophilization. Scaffolds were sterilized in ethanol and rinsed several times in phosphatebuffered saline (PBS) before use.…”

Section: Precursor Suspension Preparationmentioning

confidence: 99%

Collagen-GAG Scaffold Biophysical Properties Bias MSC Lineage Choice in the Presence of Mixed Soluble Signals

Caliari

Harley

2014

Tissue Engineering Part A

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Biomaterial strategies for regenerating multitissue structures require unique approaches. One strategy is to design scaffolds so that their local biophysical properties can enhance site-specific effects of an otherwise heterogeneous biomolecular environment. This investigation examined the role of biomaterial physical properties (relative density, mineral content) on the human mesenchymal stem cell phenotype in the presence of mixed soluble signals to drive osteogenesis or chondrogenesis. We tested a series of three-dimensional collagen-glycosaminoglycan scaffolds with properties inspired by extracellular matrix characteristics across the osteotendinous interface (tendon, cartilage, and bone). We found that selective scaffold mineralization induced a depressed chondrogenic response compared with nonmineralized groups as demonstrated by gene expression and histological analyses. Interestingly, the greatest chondrogenic response was found in a higher density, nonmineralized scaffold variant despite increased contraction and cellular condensation in lower density nonmineralized scaffolds. In fact, the lower density scaffolds demonstrated a significantly higher expression of osteogenic transcripts as well as ample mineralization after 21 days of culture. This effect may be due to local stiffening of the scaffold microenvironment as the scaffold contracts, leading to increased cell density, accelerated differentiation, and possible endochondral ossification as evidenced by a transition from a glycosaminoglycan (GAG)-rich milieu to higher mineralization at later culture times. These findings will help shape the design rules for graded biomaterials to regenerate distinct fibrillar, fibrocartilagenous, and mineralized regions of orthopedic interfaces.

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Section: Precursor Suspension Preparationmentioning

confidence: 99%

Collagen-GAG Scaffold Biophysical Properties Bias MSC Lineage Choice in the Presence of Mixed Soluble Signals

Caliari

Harley

2014

Tissue Engineering Part A

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“…These efforts have included optimization of scaffold pore structure (porosity and pore anisotropy), 32, 33 soluble factor cocktails to balance proliferation and phenotypic stability, 34, 35 glycosaminoglycan (GAG) content to mediate transient sequestration of growth factors, and structural reinforcement via the incorporation of CG membranes structures. 36 Recently we described a calcium phosphate mineralized CG (CGCaP) scaffold with potential application for bone tissue engineering and as a component of an osteotendinous repair biomaterial.…”

Section: Introductionmentioning

confidence: 99%

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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“…Also mineralization of hMSCs in the Col-GAG scaffolds occurred at the periphery whereas MC-GAG scaffolds showed good consistent mineralization throughout the scaffold. The scaffolds were relatively similar in porosity, but previous studies showed that these scaffolds differ in terms of presence of nanoparticulate calcium phosphate particles and elastic moduli which may help explain differences in mineralization [47][48] .…”

Section: Growth-factor Independent Osteogenic Induction Of Hmscsmentioning

confidence: 96%

Biomimetic Scaffolds for Osteogenesis

Yuan

Rezzadeh

Lee

2015

Receptor Clin Invest

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Skeletal regenerative medicine emerged as a field of investigation to address large osseous deficiencies secondary to congenital, traumatic, and post-oncologic conditions. Although autologous bone grafts have been the gold standard for reconstruction of skeletal defects, donor site morbidity remains a significant limitation. To address these limitations, contemporary bone tissue engineering research aims to target delivery of osteogenic cells and growth factors in a defined three dimensional space using scaffolding material. Using bone as a template, biomimetic strategies in scaffold engineering unite organic and inorganic components in an optimal configuration to both support osteoinduction as well as osteoconduction. This article reviews the various structural and functional considerations behind the development of effective biomimetic scaffolds for osteogenesis and highlights strategies for enhancing osteogenesis.

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The impact of discrete compartments of a multi-compartment collagen–GAG scaffold on overall construct biophysical properties

Cited by 45 publications

References 46 publications

Collagen-GAG Scaffold Biophysical Properties Bias MSC Lineage Choice in the Presence of Mixed Soluble Signals

Collagen-GAG Scaffold Biophysical Properties Bias MSC Lineage Choice in the Presence of Mixed Soluble Signals

Mineralized collagen scaffolds induce hMSC osteogenesis and matrix remodeling

Biomimetic Scaffolds for Osteogenesis

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