Effects of P-15 Peptide Coated Hydroxyapatite on Tibial Defect Repair In Vivo in Normal and Osteoporotic Rats

Pedersen, Rasmus Hestehave; Rasmussen, M.S.; Overgaard, Søren; Ding, Ming

doi:10.1155/2015/253858

Cited by 14 publications

(11 citation statements)

References 43 publications

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“…In a pilot study by Gomar and co‐workers, ABM/P‐15 was used as a bone graft substitute to treat delayed or nonunion fractures in various long bones in adult trauma, and they reported full consolidation in 90% of patients at an average of 4.2 months . In a recent study, ABM/P‐15 accelerated bone regeneration in 4‐month‐old osteoporotic rats with 2.8 mm cylindrical proximal tibial defect, but did not induce bone repair in normal rats with the same defect . Combining P‐15 with hydroxyapatite enhanced bone regeneration in a porcine calvarial defect model .…”

Section: Collagen‐derived Peptidesmentioning

confidence: 97%

Short Anabolic Peptides for Bone Growth

Amso

Cornish²,

Brimble

2016

Medicinal Research Reviews

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Loss of bone occurs in the age-related skeletal disorder, osteoporosis, leading to bone fragility and increased incidence of fractures, which are associated with enormous costs and substantial morbidity and mortality. Recent data indicate that osteoporotic fractures are more common than other diseases, which usually attract public attention (e.g., heart attack and breast cancer). The prevention and treatment of this skeletal disorder are therefore of paramount importance. Majority of osteoporosis medications restore skeletal balance by reducing osteoclastic activity, thereby reducing bone resorption. These agents, however, do not regenerate damaged bone tissue, leaving limited options for patients once bone loss has occurred. Recently, attention has turned to bone-anabolic agents. Such agents have the ability to increase bone mass and strength, potentially reversing structural damage. To date, only one bone-anabolic drug is available in the market. The discovery of more novel, cost-effective bone anabolic agents is therefore a priority to treat those suffering from this disabling condition. Short peptides offer an important alternative for the development of novel bone-anabolic agents given their high target binding specificity, which translates into potent activity with limited side effects. This review summarizes attempts in the identification of bone-anabolic peptides, and their development for promoting bone growth.

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Section: Collagen‐derived Peptidesmentioning

confidence: 97%

Short Anabolic Peptides for Bone Growth

Amso

Cornish²,

Brimble

2016

Medicinal Research Reviews

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“…When P15 is present at the surface of a material it functions as a substitute for collagen type I. The binding of cell surface integrins (α 2 β 1 ) to P15 leads to the production of growth factors and cytokines, which in turn stimulate matrix production and mineralisation [110]. As the integrin α 2 β 1 is known to be collagen specific, it is believed that this interaction would not compete with other cell surface integrins for FN (α IIb β 3 or α 5 β 1 ) or VN (α v β 3 ), proteins found in blood [37].…”

Section: P15 Peptidementioning

confidence: 99%

“…P15 has also received significant attention as it interacts with cells through a specific integrin, and therefore does not compete with other protein interactions [37]. This sequence is supported by a large body of in vitro studies and clinical trials, and carries specific commercial value [11,12,18,[110][111][112][113][114][115][116]. As P15 is currently available on the market, for dental (PepGen ® (Dentsply©) and orthopaedic (i-Factor ® (Cerapedics©)) applications, there is a large body of published literature surrounding its successful use, with some shown in Table 5.…”

Section: P15 Peptidementioning

confidence: 99%

“…There have been several studies demonstrating the efficacy of P15 in vivo. In animals, ANKYLOS ® (Dentsply©) and i-Factor ® (Cerapedics©) significantly enhanced bone regeneration in alveolar bone in dogs and the tibia of osteoporotic dogs, respectively, in studies from Pedersen et al [110] and Schmitt et al [118]. However, Pedersen et al also indicated that, in normal rats, bone regeneration was not accelerated when treated using i-Factor ® .…”

Section: P15 Peptidementioning

confidence: 99%

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Osteogenic Peptides and Attachment Methods Determine Tissue Regeneration in Modified Bone Graft Substitutes

Bullock

Atkinson

Gentile

et al. 2021

JFB

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The inclusion of biofunctional molecules with synthetic bone graft substitutes has the potential to enhance tissue regeneration during treatment of traumatic bone injuries. The clinical use of growth factors has though been associated with complications, some serious. The use of smaller, active peptides has the potential to overcome these problems and provide a cost-effective, safe route for the manufacture of enhanced bone graft substitutes. This review considers the design of peptide-enhanced bone graft substitutes, and how peptide selection and attachment method determine clinical efficacy. It was determined that covalent attachment may reduce the known risks associated with growth factor-loaded bone graft substitutes, providing a predictable tissue response and greater clinical efficacy. Peptide choice was found to be critical, but even within recognised families of biologically active peptides, the configurations that appeared to most closely mimic the biological molecules involved in natural bone healing processes were most potent. It was concluded that rational, evidence-based design of peptide-enhanced bone graft substitutes offers a pathway to clinical maturity in this highly promising field.

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“…The potential of ABM/P-15 on bone formation has been previously shown in preclinical and clinical studies. ABM/P-15 induces bone formation comparable to allograft in critical sized defects and implant fixation sheep models [21] and also improves bone formation in rat osteoporotic models [22]. ABM/P-15 has had comparable fusion rates as allograft in an interbody ovine fusion model [23] and in humans [24].…”

Section: Introductionmentioning

confidence: 99%

Comparison of synthetic bone graft ABM/P-15 and allograft on uninstrumented posterior lumbar spine fusion in sheep

et al. 2019

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BackgroundSpinal fusion is a commonly used procedure in spinal surgery. To ensure stable fusion, bone graft materials are used. ABM/P-15 (commercial name i-Factor™ Flex) is an available synthetic bone graft material that has CE approval in Europe. This peptide has been shown to improve bone formation when used in devices with fixation or on bone defects. However, the lack of external stability and large graft size make posterolateral lumbar fusion (PLF) a most challenging grafting procedure. This prospective randomized study was designed to evaluate early spinal fusion rates using an anorganic bovine-derived hydroxyapatite matrix (ABM) combined with a synthetic 15 amino acid sequence (P-15)–ABM/P-15 bone graft, and compared with allograft in an uninstrumented PLF model in sheep. The objective of this study was to assess fusion rates when using ABM/P-15 in uninstrumented posterolateral fusion in sheep.MethodsTwelve Texas/Gotland mixed breed sheep underwent open PLF at 2 levels L2/L3 and L4/L5 without fixation instruments. The levels were randomized so that sheep received an ABM graft either with or without P15 coating. Sheep were euthanized after 4.5 months and levels were harvested and evaluated with a micro-CT scanner and qualitative histology. Fusion rates were assessed by 2D sections and 3D reconstruction images and fusion was defined as intertransverse bridging.ResultsThere was 68% fusion rate in the allograft group and an extensive migration of graft material was noticed with a fusion rate of just 37% in the ABM/P-15 group. Qualitative histology showed positive osteointegration of the material and good correlation to scanning results.ConclusionsIn this PLF fusion model, ABM/P15 demonstrated the ability to migrate when lacking external stability. Due to this migration, reported fusion rates were significantly lower than in the allograft group. The use of ABM/P15 as i-Factor™ Flex may be limited to devices with fixation and bone defects.

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Effects of P-15 Peptide Coated Hydroxyapatite on Tibial Defect Repair In Vivo in Normal and Osteoporotic Rats

Cited by 14 publications

References 43 publications

Short Anabolic Peptides for Bone Growth

Short Anabolic Peptides for Bone Growth

Osteogenic Peptides and Attachment Methods Determine Tissue Regeneration in Modified Bone Graft Substitutes

Comparison of synthetic bone graft ABM/P-15 and allograft on uninstrumented posterior lumbar spine fusion in sheep

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