Bioactivation of an anorganic bone matrix by P-15 peptide for the promotion of early bone formation

Thorwarth, Michael; Schultze‐Mosgau, Stefan; Wehrhan, Falk; Keßler, Peter; Srour, Safwan; Wiltfang, Jens; Schlegel, Karl Andreas

doi:10.1016/j.biomaterials.2005.02.023

Cited by 48 publications

(59 citation statements)

References 37 publications

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“…Furthermore, the 9.0 ± 7.3% of residual ABM/P-15 revealed by histomorphometry may have continued to form new bone in vivo and added to the percentage of new bone formation, thus making the difference between the mean scores of the treatments even smaller with additional time (Table 3). The successful bone formation results achieved in this study with ABM/P-15 are consistent with results obtained in other preclinical models [14][15][16], dental models [17][18][19][20][21][22][23][24][25][26], and the pilot orthopaedic model [9].…”

Section: Discussionsupporting

confidence: 89%

“…Thus, patient satisfaction in lumbar fusions would likely rise if bone graft harvesting could be avoided by using a synthetic agent, like ABM/P-15, that is as effective as autologous bone. P-15 has been shown to be effective in several preclinical models [14][15][16]. A study by Thorwarth et al [15] studied the effectiveness of P-15 in porcine skull defects by creating four different treatment groups: autogenous bone, a porous algae-derived hydroxyapatite (adHA), P-15 and adHA, and P-15 and adHA combined with 25% autogenous bone.…”

Section: Discussionmentioning

confidence: 99%

“…Overall, the properties of ABM/P-15 provide a novel approach to facilitating bone growth while avoiding the additional morbidities associated with the harvest of autograft bone or the potential side effects and high cost of osteoinductive agents. P-15 has been shown to be effective in several preclinical models [14][15][16]. A study by Thorwarth et al [15] studied the effectiveness of P-15 in porcine skull defects while Scarano et al [14] studied ABM/P-15 in 8-mm tibial defects in rabbits.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion model

et al. 2010

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A prospective, randomized study was performed in an ovine model to compare the efficacy of an anorganic bovine-derived hydroxyapatite matrix combined with a synthetic 15 amino acid residue (ABM/P-15) in facilitating lumbar interbody fusion when compared with autogenous bone harvested from the iliac crest. P-15 is a biomimetic to the cell-binding site of Type-I collagen for bone-forming cells. When combined with ABM, it creates the necessary scaffold to initiate cell invasion, binding, and subsequent osteogenesis. In this study, six adult ewes underwent anterior-lateral interbody fusion at L3/L4 and L4/L5 using PEEK interbody rings filled with autogenous bone at one level and ABM/P-15 at the other level and no additional instrumentation. Clinical CT scans were obtained at 3 and 6 months; micro-CT scans and histomorphometry analyses were performed after euthanization at 6 months. Clinical CT scan analysis showed that all autograft and ABM/P-15 treated levels had radiographically fused outside of the rings at the 3-month study time point. Although the clinical CT scans of the autograft treatment group showed significantly better fusion within the PEEK rings than ABM/P-15 at 3 months, micro-CT scans, clinical CT scans, and histomorphometric analyses showed there were no statistical differences between the two treatment groups at 6 months. Thus, ABM/P-15 was as successful as autogenous bone graft in producing lumbar spinal fusion in an ovine model, and it should be further evaluated in clinical studies.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion model

et al. 2010

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“…Natural collagen exhibits a unique CD spectrum characterized by a positive peak at around 220 nm, a crossover near 213 nm, and a large negative peak at approximately 197 nm. 48,49 Non-templated (Pro-Hyp-Gly) 10 was used as a stable prototype of a triple helix, while (Pro-ProGly) 3 and calf-skin collagen were used as a negative control and collagen model, respectively. The PT-assembled collagen peptides and CP3 exhibited CD spectra features characteristic of a collagen-like triple helix, including a positive peak around 220-225 nm and a large negative trough near 200 nm ( Figure 2), similar to natural collagen and (Pro-Hyp-Gly) 10 (Figure 2d).…”

Section: Resultsmentioning

confidence: 99%

The Specific Recognition of a Cell Binding Sequence Derived from Type I Collagen by Hep3B and L929 Cells

Khew

Tong

2007

Biomacromolecules

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In this study, the affinity of two different cell types toward a specific cell binding sequence (Gly-Phe-Hyp-Gly-Glu-Arg or GFOGER) derived from type I collagen using peptide template (PT)-assembled collagen peptides of different triple helicity as a model for natural collagen is examined. A series of biophysical studies, including melting curve analysis and circular dichroism spectroscopy, demonstrated the presence of stable triple-helical conformation in the PT-assembled (GPO)3-GFOGER-(GPO)3, (GPO)-GFOGER-(GPO), and (Pro-Hyp-Gly)5 solution. Conversely, non-templated peptides, except (GPO)3-GFOGER-(GPO)3, showed no evidence of assembly into triple-helical structure. Biological assays, including cell adhesion, competitive inhibition, and immunofluorescence staining, revealed a correlation of triple-helical conformation with the cellular recognition of GFOGER in an integrin-specific manner. The triple helix was shown to be important, but not crucial for cell adhesion to native collagen. Hep3B and L929 cells displayed significant differences in the recognition of GFOGER, mainly because of the differences in their expression of specific integrin receptors for collagen. For example, PT-assembled (GPO)3-GFOGER-(GPO)3 was shown to perform comparably to collagen for L929, but not Hep3B, cell adhesion. The result showed that a specific cell binding motif may not fully mimic the extracellular matrix (ECM) microenvironment, suggesting the need to use a combination of two or more cell binding sequences for targeting a wide range of integrin receptors expressed by a specific cell type to better mimic the ECM.

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“…Histological and histomorphometrical results of these studies showed an increase and an acceleration of bone formation when compared to the control sites. This point was also revealed in the study of Thorwarth on the filling of bone cavities created in pig skulls [46]. The filling materials studied separately were the autogenous bone and the two biomaterials used for the present study, PepGen P-15 ® and Osteograph ® N/700.…”

Section: Discussionmentioning

confidence: 96%

Ultrastructure and Analytical Features of the Sinus Floor Augmentation with Osteograph<sup>®</sup> and PepGen P-15<sup>®</sup>

Dahlet¹,

Boukari²,

Collavini³

et al. 2013

JBNB

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The aim of the present study was to investigate an inorganic bovine-derived hydroxyapatite bone substitute (Osteograph ® ) mixed with the same biomaterial coated with a synthetic peptide (P-15) analogue of collagen ). This blend of bone replacement materials was used for sinus floor augmentation. Assessments were carried out by using histology methods, transmission electron microscopy (TEM) and microanalysis (EDX). Ultrastructural and analytical features of the interfaces between the graft material and the peri-biomaterial tissues were evaluated six months after implantation. Our findings clearly show that newly-formed crystallites first develop at the surface of implanted crystals. Histological investigations revealed new bone tissue linking biomaterial particles together. TEM assessments pointed out that lamellar bone was generally separated from the graft material by a layer of woven bone measuring between 1 and 1.5 µm in thickness. Although calcified bone tissue was observed in direct contact with bone filling particles, the presence of mineralized granular material around implanted particles was also noticed. No characteristic periodic striation of mineralized collagen was evident within that mineralized structure. Chemical analyses (TEM-EDX) realized at different locations of newly formed mineralized granular substance along the interface revealed average Ca/P ratios ranging between 1.02 and 1.63. The different, concomitantly occurring, aforementioned structural features of the interfaces strongly suggested that the host responses to the used biomaterial blend resulted from dynamic osseointegration phenomena related to various interfacial mechanisms. Nevertheless, the biological response to the bone graft material appeared clinically and histologically satisfactory.

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Bioactivation of an anorganic bone matrix by P-15 peptide for the promotion of early bone formation

Cited by 48 publications

References 37 publications

Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion model

Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion model

The Specific Recognition of a Cell Binding Sequence Derived from Type I Collagen by Hep3B and L929 Cells

Ultrastructure and Analytical Features of the Sinus Floor Augmentation with Osteograph<sup>®</sup> and PepGen P-15<sup>®</sup>

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Bioactivation of an anorganic bone matrix by P-15 peptide for the promotion of early bone formation

Cited by 48 publications

References 37 publications

Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion model

Evaluation of ABM/P-15 versus autogenous bone in an ovine lumbar interbody fusion model

The Specific Recognition of a Cell Binding Sequence Derived from Type I Collagen by Hep3B and L929 Cells

Ultrastructure and Analytical Features of the Sinus Floor Augmentation with Osteograph&lt;sup&gt;&#174;&lt;/sup&gt; and PepGen P-15&lt;sup&gt;&#174;&lt;/sup&gt;

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Ultrastructure and Analytical Features of the Sinus Floor Augmentation with Osteograph<sup>®</sup> and PepGen P-15<sup>®</sup>