A porcine collagen-derived matrix as a carrier for recombinant human bone morphogenetic protein-2 enhances spinal fusion in rats

Miyazaki, Masashi; Morishita, Yuichiro; He, Wubing; Hu, Ming; Sintuu, Chananit; Hymanson, Henry J.; Falakassa, Jonathan; Tsumura, Hiroshi; Wang, Jeffrey C.

doi:10.1016/j.spinee.2008.08.009

Cited by 54 publications

(51 citation statements)

References 29 publications

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“…41 The nanofiber scaffold component of TrioMatrix 1 is created from individual strands of porcine skin collagen, also referred to as ''E-Matrix'' in a prior study. 42 By ''unraveling'' the collagen triple helix, the gelatin monomers are made available to allow cell and protein interactions. This nanofiber polymer has been shown to have beneficial effects on tissue growth.…”

Section: Discussionmentioning

confidence: 99%

“…This nanofiber polymer has been shown to have beneficial effects on tissue growth. 42 Furthermore, the hydroxyapatite in TrioMatrix 1 is also formulated through nanoscale components to better mimic human bone mineral than conventional carriers. Ceramic carriers have been shown to provide compression-resistant structure in bone healing, both as a bulking agent and a successful bone graft extender in lumbar posterolateral spine fusion.…”

Section: Discussionmentioning

confidence: 99%

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Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

Hsu¹,

Polavarapu²,

Riaz³

et al. 2011

Journal Orthopaedic Research

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The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spine fusion has led to concerns regarding a potential accompanying inflammatory response. This study evaluates a combination therapy (TrioMatrix 1 ; Pioneer Surgical, Inc., Marquette, MI) comprised of a demineralized bone matrix (DBM), hydroxyapatite, and a nanofiber-based collagen scaffold in a rodent spine fusion model. Thirty-six athymic rats that underwent a posterolateral intertransverse spinal fusion were randomly assigned to 1 of 5 treatment groups: absorbable collagen sponge alone (ACS, negative control), 10 mg rhBMP-2 on ACS (positive control), TrioMatrix 1 , Grafton 1 (Osteotech, Inc., Eatontown, NJ), and DBX 1 (Synthes, Inc., West Chester, PA). Both TrioMatrix 1 and rhBMP-2-treated animals demonstrated 100% fusion rates as graded by manual palpation scores 8 weeks after implantation. This rate was significantly greater than those of the ACS, Grafton 1 , and DBX 1 groups. Notably, the use of TrioMatrix 1 as evaluated by microCT quantification led to a greater fusion mass volume when compared to all other groups, including the rhBMP-2 group. T2-weighted axial MRI images of the fusion bed demonstrated a significant host response associated with a large fluid collection with the use of rhBMP-2; this response was significantly reduced with the use of TrioMatrix 1 . Our results therefore demonstrate that a nanocomposite therapy represents a promising, cost-effective bone graft substitute that could be useful in spine fusions where BMP-2 is contraindicated.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

Hsu¹,

Polavarapu²,

Riaz³

et al. 2011

Journal Orthopaedic Research

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“…Bone formation in these groups was compared to our previously established positive control of absorbable collagen sponges impregnated with 10 mg recombinant human BMP-2. [32][33][34][35] After anesthesia induction by isoflurane inhalation, the surgical site was shaved and prepped. A posterior midline incision was made over the skin of the lumbar spine.…”

Section: Surgical Procedures and Study Groupsmentioning

confidence: 99%

Delivery of Lyophilized Nell-1 in a Rat Spinal Fusion Model

Lee

Whang

et al. 2010

Tissue Engineering Part A

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Nell-1 (Nel-like molecule-1; Nel: protein strongly expressed in neural tissue containing epidermal growth factorlike domain) is a promising osteoblast-specific growth factor for osteoinductive therapies that may circumvent adverse effects, such as nonspecific function and ectopic bone formation, associated with more established osteogenic growth factors such as bone morphogenetic proteins. Beta-tricalcium phosphate (b-TCP), an osteoconductive, biodegradable ceramic biomaterial, has been used successfully to deliver osteoinducers for bone regeneration. The aim of this study was to develop a carrier system for efficiently delivering biologically active Nell-1 protein. After a 40% initial burst release, b-TCP particles retained the majority of adsorbed Nell-1 protein in vitro. To test this system in vivo, L4/L5 spinal fusion was performed in three groups of rats (n ¼ 8 each): (1) 5 mg Nell-1 in b-TCP/demineralized bone matrix putty (DBX); (2) 2.5 mg Nell-1 in b-TCP/DBX; (3) b-TCP/DBX only. Fusion was assessed by radiography, palpation, microcomputed tomography, and histological analysis. After 4 weeks, 75% of Nell-1-treated animals exhibited fusion, with a significant increase in new bone volume, whereas only 25% of Nell-free control animals exhibited fusion. Our findings suggest that b-TCP/DBX can increase both the biochemical stability and biological efficiency of Nell-1 protein.

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“…20,21 The purpose of the present study was to investigate the enhancement of the effects of ExCNFs by BMP and examine the feasibility and safety of ExCNFs in clinical applications using a rat femoral fracture model.…”

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confidence: 99%

Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

Miyazaki

Toyoda

Yoshiiwa

et al. 2014

Journal Orthopaedic Research

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Exfoliated carbon nanofibers (ExCNFs) are expected to serve as excellent scaffolds for promoting and guiding bone-tissue regeneration. We aimed to enhance the effects of ExCNFs with bone morphogenetic proteins (BMPs) and examine their feasibility and safety in clinical applications using a rat femoral fracture model. Group I (n ¼ 16) animals were implanted with control MedGEL. Group II (n ¼ 17) animals were implanted with MedGEL containing ExCNFs. Group III (n ¼ 15) animals were implanted with MedGEL containing 1 mg rhBMP-2. Group IV (n ¼ 15) animals were implanted with MedGEL containing 1 mg rhBMP-2 and ExCNFs. The rats were euthanized after 6 weeks, and their fractured femurs were explanted and assessed by manual palpation, radiographs, and highresolution microcomputerized tomography (micro-CT); the femurs were also subjected to biomechanical and histological analysis. The fusion rates in Group IV (73.3%) were considerably higher than those in Groups I (25. Keywords: exfoliated carbon nanofiber; bone morphogenetic protein; fracture healing; rat femoral fracture model; scaffold Bone morphogenetic proteins (BMPs) are members of the transforming growth factor b superfamily and are powerful osteoinductive molecules. The osteoinductive effects of recombinant human BMPs (rhBMPs) in surgical procedures such as fracture repair, healing of critical-size bone defects, and spinal fusion have been demonstrated in animal models and clinical trials; furthermore, rhBMP-2 and rhBMP-7 have been approved for clinical use. [1][2][3][4][5] Unfortunately, the results of clinical trials show that high doses of BMPs are required to induce adequate bone fusion, as the molecules are soluble and easily diffuse away from the fusion site, becoming inactivated in vivo. 6 In addition, the usefulness of BMPs is limited by their high costs. To address these problems, a number of strategies are being developed to generate safer, less expensive, and more efficacious spinal fusion using rhBMP. However, the efficient immobilization of BMPs onto carriers at low dosage while maintaining desirable in vivo regenerative action remains as a major challenge in bone regeneration research and practice. 7,8 The required rhBMP-2 level in humans, even for the FDA-approved collagen sponge-incorporated treatment, is much higher (over six orders of magnitude greater) than that used for in vitro cell level evaluation and in vivo animal studies. 7,9 Several ongoing investigations aim to develop a scaffold that functions as a delivery vehicle, providing cells with a more controlled and sustained release of bioactive molecules to maintain the local growth factor concentration within the therapeutic range.Carbon nanotubes (CNTs) have received much attention because of their interesting properties, including their exceptional mechanical 10 and high electrical and thermal conductivity, 11 which facilitate their use as reinforcements or additives in materials such as plastics, metals, and ceramics to improve the properties of the materials and introduce nove...

show abstract

A porcine collagen-derived matrix as a carrier for recombinant human bone morphogenetic protein-2 enhances spinal fusion in rats

Cited by 54 publications

References 29 publications

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

Nanocomposite therapy as a more efficacious and less inflammatory alternative to bone morphogenetic protein‐2 in a rodent arthrodesis model

Delivery of Lyophilized Nell-1 in a Rat Spinal Fusion Model

Enhancement of the Effects of Exfoliated Carbon Nanofibers by Bone Morphogenetic Protein in a Rat Femoral Fracture Model

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