Bioengineering an Osteoinductive Treatment for Bone Healing Disorders: A Small Animal Case Series

Abstract

The aim of this article was to study clinical and radiographic outcomes following treatment of bone healing disorders with a novel osteoinductive system that utilizes poly (ethyl acrylate), fibronectin and an ultra-low concentration of recombinant human bone morphogenetic protein-2. A case series of nine dogs and two cats were treated, and clinical records and radiographs were reviewed. Radiographs were scored by two blinded observers using the modified Radiographic Union Score for Tibial Fractures. Long-term follow-up was obtained using the Canine Orthopaedic Index and Feline Musculoskeletal Pain Index. Follow-up data were available for 11 treatments (10 cases). Complications: three minor, three major, one catastrophic (non-union requiring amputation). Lameness median 320 (range: 42–1,082) days postoperatively: ‘sound’ (three cases), ‘subtle’ (two), ‘mild’ (three), ‘moderate’ (one), and ‘non-weightbearing’ (one). The attending clinician judged 9 of 11 treatments achieved radiographic union; modified Radiographic Union Score for Tibial Fractures observers 1 and 2 agreed with the clinician in 8/9 and 5/9 treatments respectively. Long-term Canine Orthopaedic Index scores for five dogs median 650 (range: 544–1,724) days postoperatively: 15/64 (median) for four dogs with acceptable outcomes, 30/64 in one dog with a poor outcome. Feline Musculoskeletal Pain Index scores for two cats 433 and 751 days postoperatively: 48/60 and 60/60. Eight of 10 cases were sound or showed subtle or mild lameness in the short- or long-term, and radiographic union occurred in the majority of treatments.

Bioactive coatings on 3D printed polycaprolactone scaffolds for bone regeneration: a novel murine femur defect model for examination of the biomaterial capacity for repair

“…ELP coating on a solid scaffold material has been shown to enhance integration between the scaffold and bone but had not been found to significantly contribute to bone formation when compared to uncoated controls [12]. The PEA/FN/BMP-2 coating has previously been applied with successful bone formation in murine radial defects and veterinary clinical cases, when combined with autograft [13, 34]. However, it was not found to produce reliable, consistent bone volumes in this study, potentially as a consequence of the PEA/FN/BMP-2 coating relying on a greater surface area such as on porous granular materials to deliver a critical mass of BMP-2 to take advantage of the PEA/FN/BMP-2 reciprocal binding.…”

Bioactive coatings on 3D printed scaffolds for bone regeneration: Use of Laponite™ to deliver BMP-2 for bone tissue engineering – progression throughin vitro, chorioallantoic membrane assay and murine subcutaneous model validation

“…Covalent approaches such as the application of a chemical deposition technique to coat titanium with glycidyl methacrylate (GMA) to bind rhBMP-2 provided high results of rhBMP-2 bound to the titanium substrates (243.9 ± 25.7 ng), compared to physical adsorption (40.2 ± 32.7 ng), however the BMP-2 adsorbed to the surface of the titanium was not compared to the mass of BMP-2 bound via GMA with regard to osteogenic differentiation of cells upon the scaffold [15]. To mitigate and avoid adverse effects and maintain the BMP-2 in situ to induce bone formation, the use of a low concentration/mass of BMP-2 adhered to poly(ethyl acrylate) and fibronectin coated materials has been applied by the Salmeron-Sanchez group, with bone healing demonstrated in a murine radial defect study as well as in veterinary clinical cases [7, 16]. Despite these methods of immobilised delivery of growth factors to tissues, further optimisation is required to ensure the growth factor is active and at the correct concentration and mass to produce a biological effect.…”

Bioactive coatings on 3D printed scaffolds for bone regeneration: Translation fromin vitrotoin vivomodels and the impact of material properties and growth factor concentration

“…Subsequently, a mouse radial defect study illustrated enhanced bone repair with a polyimide ‘sleeve’ coated in PEA/FN/BMP-2 compared to control ‘sleeves’ [15]. The clinical use of this FN and BMP-2 growth factor interaction on PEA has been validated in veterinary cases of complicated, non-healing fractures [13, 16]. Furthermore, in comparison to other clinical reports using 0.5 mg/mL of BMP-2 solution for non-union cases, this method of binding BMP-2 to PEA/FN utilises lower concentrations of BMP-2 [17].…”