Intervertebral Disc Tissue Engineering Using a Novel Hyaluronic Acid–Nanofibrous Scaffold (HANFS) Amalgam

Nesti, Leon J.; Li, Wan‐Ju; Shanti, Rabie M.; Jiang, Yi; Jackson, Wesley M.; Freedman, Brett A.; Kuklo, Timothy R.; Giuliani, Jeffrey R.; Tuan, Rocky S.

doi:10.1089/ten.tea.2008.0215

Cited by 180 publications

(133 citation statements)

References 62 publications

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“…124 Others have investigated multicomponent scaffolds, where a gelatinous core is established (by injection) in the mid-substance of a nanofibrous sheet for intervertebral disc applications. 125 Still others have begun to investigate how layers of nanofibers can be seeded with cells, and then stacked to achieve anatomic forms such as periodontal ligament 126 as well as more complicated structures recreating the anatomic form of the IVD and the knee meniscus 127,128 (Fig. 15).…”

Section: Reconstituting Anatomic Formmentioning

confidence: 99%

Engineering on the Straight and Narrow: The Mechanics of Nanofibrous Assemblies for Fiber-Reinforced Tissue Regeneration

Mauck

Baker

Nerurkar

et al. 2009

Tissue Engineering Part B: Reviews

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191

177

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Tissue engineering of fibrous tissues of the musculoskeletal system represents a considerable challenge because of the complex architecture and mechanical properties of the component structures. Natural healing processes in these dense tissues are limited as a result of the mechanically challenging environment of the damaged tissue and the hypocellularity and avascular nature of the extracellular matrix. When healing does occur, the ordered structure of the native tissue is replaced with a disorganized fibrous scar with inferior mechanical properties, engendering sites that are prone to re-injury. To address the engineering of such tissues, we and others have adopted a structurally motivated approach based on organized nanofibrous assemblies. These scaffolds are composed of ultrafine polymeric fibers that can be fabricated in such a way to recreate the structural anisotropy typical of fiber-reinforced tissues. This straight-and-narrow topography not only provides tailored mechanical properties, but also serves as a 3D biomimetic micropattern for directed tissue formation. This review describes the underlying technology of nanofiber production and focuses specifically on the mechanical evaluation and theoretical modeling of these structures as it relates to native tissue structure and function. Applying the same mechanical framework for understanding native and engineered fiber-reinforced tissues provides a functional method for evaluating the utility and maturation of these unique engineered constructs. We further describe several case examples where these principles have been put to test, and discuss the remaining challenges and opportunities in forwarding this technology toward clinical implementation.

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Section: Reconstituting Anatomic Formmentioning

confidence: 99%

Engineering on the Straight and Narrow: The Mechanics of Nanofibrous Assemblies for Fiber-Reinforced Tissue Regeneration

Mauck

Baker

Nerurkar

et al. 2009

Tissue Engineering Part B: Reviews

Self Cite

191

177

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“…In addition, the presence of the CP peptide sequence which is normally present in chondrocytes and plays an integral role in cartilage formation and Col-II binding may also have resulted in higher affinity of the cells toward Construct II. Col-I and Col-II are both present in fibrocartilage and therefore Construct I may be more suitable for TE of intervertebral disc space, while Construct II may be more apt for hyaline or elastic cartilage TE [114]. Thus, our results indicate that both constructs provided stable matrices for cell proliferation, adhesion and growth and that the adhesion of the cells depended largely on the peptide composition.…”

Section: Cell Morphology and Adhesionmentioning

confidence: 67%

Comparison of Engineered Peptide-Glycosaminoglycan Microfibrous Hybrid Scaffolds for Potential Applications in Cartilage Tissue Regeneration

Romanelli

Knoll

Santora

et al. 2015

Fibers

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Advances in tissue engineering have enabled the ability to design and fabricate biomaterials at the nanoscale that can actively mimic the natural cellular environment of host tissue. Of all tissues, cartilage remains difficult to regenerate due to its avascular nature. Herein we have developed two new hybrid polypeptide-glycosaminoglycan microfibrous scaffold constructs and compared their abilities to stimulate cell adhesion, proliferation, sulfated proteoglycan synthesis and soluble collagen synthesis when seeded with chondrocytes. Both constructs were designed utilizing self-assembled Fmoc-protected valyl cetylamide nanofibrous templates. The peptide components of the constructs were varied. For Construct I a short segment of dentin sialophosphoprotein followed by Type I collagen were attached to the templates using the layer-by-layer approach. For Construct II, a short peptide segment derived from the integrin subunit of Type II collagen binding protein expressed by chondrocytes was attached to the templates followed by Type II collagen. To both constructs, we then attached the natural polymer N-acetyl glucosamine, chitosan. Subsequently, the glycosaminoglycan chondroitin sulfate was then attached as the final layer. The scaffolds were characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), atomic force microscopy and scanning electron microscopy. In vitro culture studies were carried out in the presence of chondrocyte cells for OPEN ACCESSFibers 2015, 3 266 both scaffolds and growth morphology was determined through optical microscopy and scanning electron microscopy taken at different magnifications at various days of culture. Cell proliferation studies indicated that while both constructs were biocompatible and supported the growth and adhesion of chondrocytes, Construct II stimulated cell adhesion at higher rates and resulted in the formation of three dimensional cell-scaffold matrices within 24 h. Proteoglycan synthesis, a hallmark of chondrocyte cell differentiation, was also higher for Construct II compared to Construct I. Soluble collagen synthesis was also found to be higher for Construct II. The results of the above studies suggest that scaffolds designed from Construct II be superior for potential applications in cartilage tissue regeneration. The peptide components of the constructs play an important role not only in the mechanical properties in developing the scaffolds but also control cell adhesion, collagen synthesis and proteoglycan synthesis capabilities.

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“…Promising results have been reported 24 weeks after nucleotomy with additional intradiscal application of different HA formulations in monkeys [9]. Latest studies focused on cell-free disc implants and found promising results for HA-based biomaterials [10,11]. Cell-free implants made of polyglycolic acid (PGA) and HA induced the regeneration of articular cartilage in a sheep model [12].…”

Section: Introductionmentioning

confidence: 99%

Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model

et al. 2012

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Introduction Disc degeneration and re-herniation after nucleotomy procedures are common problems. Simultaneous application of hyaluronic acid (HA)-based matrix has been proposed to limit disc degeneration. This, however, is hampered by loss of the substituted matrix out of the disc. Hence, in situ polymerization of the injected matrix with ultraviolet light (UVL) directly used after injection may be useful. Therefore, this study evaluates a new HA/collagen hydrogel matrix with in situ polymerization after implantation in an established porcine nucleotomy model. Materials and methods 12 mature minipigs were used. A total of 60 lumbar discs were analyzed. 36 discs underwent partial nucleotomy with a 16G biopsy needle. Of those, 24 discs received matrix (porcine nucleus pulposus collagenous scaffold component and chemically modified HA) which was in situ polymerized using UVL immediately after transplantation. 12 nucleotomized discs and 24 non-nucleotomized discs served as controls. After 24 weeks, animals were killed. X-rays, MRIs, histology, and gene expression analysis were done. Results Disc height was reduced equally after sole nucleotomy and nucleotomy with HA treatment and in MRIs signal intensity decreased. For both nucleotomy groups, the nucleus histo-degeneration score showed a significant increase compared to controls. In histology, HA treatment resulted in more scarring and inflammation in the annulus. Gene expression of catabolic MMPs was up-regulated, whereas IFN-gamma, IL-6, and IL-1b were unchanged. Conclusion Although nucleotomy and administration of the implant material did not cause generalized inflammation of the disc, localized annular damage with annulus inflammation and scarring resulted in detrimental degenerative disc changes. As a result, therapeutic strategies should strongly focus on the prevention of annular damage or techniques for annular repair to remain disc integrity.

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Intervertebral Disc Tissue Engineering Using a Novel Hyaluronic Acid–Nanofibrous Scaffold (HANFS) Amalgam

Cited by 180 publications

References 62 publications

Engineering on the Straight and Narrow: The Mechanics of Nanofibrous Assemblies for Fiber-Reinforced Tissue Regeneration

Engineering on the Straight and Narrow: The Mechanics of Nanofibrous Assemblies for Fiber-Reinforced Tissue Regeneration

Comparison of Engineered Peptide-Glycosaminoglycan Microfibrous Hybrid Scaffolds for Potential Applications in Cartilage Tissue Regeneration

Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model

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