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Instructive Bone Grafts

In 2 million orthopaedic procedures per year, bone grafting is required to ensure bone growth in defect sites. Autograft (patient-own bone) harvesting is the standard bone grafting technique and consists of bone taken from one area of the patient and placed at the defect site. Disadvantages of this technique are significant morbidity and pain at the removal site and lack of adequate autograft material. Patients often cannot be treated appropriately due to the lack of sufficient autograft.

 

Xpand Biotechnology is developing a new generation orthopaedic materials: Instructive Bone Grafts. Xpand’s Instructive Bone Grafts have the same performance as the gold standard patient-own bone (inducing bone growth at defect sites), but are available in abundant quantities without any adverse effects on the patient.

 

Instructive Bone Grafts developed by Xpand can be divided into Granules, Putties & Injectables and mechanically strong composites. They are targeted at the dental & craniomaxillofacial market and at various orthopedic market segments such as the € 1 billion spinal market and the fast growing hip and knee revision surgery market.

 

Unique about Xpand’s Instructive Bone Grafts is that they do not contain growth factors or cells but induce the formation of bone by attracting the patient’s own stem cells to the defect site and stimulate these cells to make autologous bone (in situ bone tissue regeneration). This action is due to the presence of defined surface micro- and nanostructural properties. Xpand’s Instructive Bone Grafts comprise a completely new class of inorganic bone inducing materials.

 

Pre-clinical studies have unambiguously shown the potent effect of calcium phosphate ceramic microstructural features on ectopic (intramuscular) bone induction (Figures 1&2). It was further shown that micro-structured non-macroporous microparticles are potent bone inducing materials (allowing the formulation of Injectables and Putties (Figure 3)). Finally, we have shown that this technology allows the formation of bone inducing composites by combining nano-shaped apatite with an appropriate polymeric matrix (Figure 4). This allows the preparation of mechanically strong bone inducing materials for e.g. revision surgery.

 

Figure 1. Formation of three distinct surface microstructural features on chemically similar calcium phosphate ceramics by means of altering processing and sintering conditions

 

Figure 2. Tissue response following implantation of the three ceramic microstructures (Figure 1) for 12 weeks in the dorsal muscle of canines. Note the abundant bone induction in the material with treatment 1, whereas the absence of bone in treatment 3. Since no growth factors or cells were implanted, bone formation is merely the result of the implant surface microstructure.

 

Figure 3. Bone induction as a result of intramuscular implantation of a large volume of surface microstructures tricalcium phosphate microparticles for 12 weeks in the dorsal muscle of canines. Note abundant bone formation (pink) around the ceramic microparticles (black). Field width is 2.5cm indicating that within 12 weeks, a solid piece of bone has been formed measuring approximately 1x2.5cm.

 

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Figure 4. Bone induction around a polylactic acid/nano-hydroxyapatite composite after 12 weeks of implantation in the dorsal muscle of canines.