P-15 small peptide bone graft substitute in the treatment of non-unions and delayed union. A pilot clinical trial

Abstract

Treatment of non-unions and delayed unions often requires osteogenic material. Recently, a biomimetic bone matrix that simulates the cellular environment of hard tissue, identified as P-15, was introduced to the orthopaedic community. A total of 22 patients with mal-union or delayed union fractures was treated from June 2000 to October 2003 with P15- bone graft substitute (P15-BGS) in the site of fracture and mostly with internal fixation. Patients were examined by independent radiographic analysis. Assessment criteria included time elapsed until bone bridging and time to full consolidation. In addition, histological assessment of the callus was done at the time of recovery of metal implants in five patients. Full consolidation was achieved in 90% (20 out of 22) of the patients treated with P15-BGS. The average time for full consolidation was 4.2 months. Histological assessment of the fracture callus in five of the patients confirmed the positive clinical and radiographic results. P15-BGS appears to offer a safe, economical and clinically useful alternative to autograft in the repair of ununited fractures. These results compare favourably with those in the published literature as an alternative to autograft.

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

“…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].…”

“…A pilot study by Gomar et al [9] used ABM/P-15 as a bone graft substitute to treat delayed or non-unions in various long bones in adult trauma. The study reported full consolidation in 90% of patients (20 of 22) at an average of 4.2 months.…”

“…Ideally, with unlimited funding, the addition of 6 weeks and 3 month histologic evaluations would have been ideal. However, we chose 3 and 6 months as our time points for this pilot study based on previous studies reporting variable rates of fusion ranging from 3 to 12 months [9,15,18,26,29,35]. As for the high fusion rates, a control with empty PEEK rings would likely have resulted in a low fusion rate.…”

“…The mineral component (ABM) provides the necessary calcium phosphate and three-dimensional matrix needed for cellular invasion, while P-15 modulates cell binding by acting as an attachment factor for the a2-b1 integrin on the surface of boneforming cells. Attachment of these cells initiates a cascade of intra-cellular signaling that leads to extracellular matrix and factor production, cell differentiation, and subsequent osteogenesis [5,[8][9][10][11][12][13]. In an in vitro study by Yang et al [13] they showed that ABM/P-15 significantly stimulated human osteoblast synthesis of bioactive BMP-2 and alkaline phosphatase-specific activity of human bone marrow cells under both basal and osteogenic conditions.…”

Covalent attachment of P15 peptide to titanium surfaces enhances cell attachment, spreading, and osteogenic gene expression

“…12 P15/ABM TM (Cerapedics, Westminster, CO) has also been used clinically and shown to improve osteointegration in spinal fusion studies. [13][14][15] Numerous attempts to improve osteointegration of Ti implants have been attempted with varying degrees of success. 16,17 Recent attention has been focused on the immobilization of small bioactive molecules on the implant surface.…”