Development and commercialisation of a polymer/ceramic bone graft

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• Development and commercialisation of a
  polymer/ceramic bone graft

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Team

• Dr. Gouher Rabani - Project lead
• Prof. Mark Bradley - Professor at The University
  of
• Edinburgh
• Dr Ian Muirhead - Commercial Champion

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Presentation Outline

• Vision
• Background
• Market
• Technology
• In Vitro and In Vivo testing
• Ageing studies
• Next Steps

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Vision
To commercialise a unique bone graft substitute,
which will be marketed under the name
Osteoconnex, through the spin-out of a Scottish
based high-growth company
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Background

• PoC project focused on a bone forming scaffold
  (Osteoconnex)
• Marketing activities conducted to define optimal
  market requirements and commercialisation drivers
• Refined product specifications to fit market
  requirements and end-user needs

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The Market
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Bone Graft Substitute (BGS) Market

• Global market worth over 1.9B set to increase to
  3.3B by 2017
• US Market worth over 1.3B set to increase to
  2.2B by 2017
• European market is estimated to be worth 500M

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BGS Market Segmentation
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6
16
8
9
13
10
12
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• Failings of Current Products

• Allograft Demineralised Bone Matrix
• Reliant on donated tissue
• Quality variation
• Risk of disease transmission
• Synthetic
• Fracture or extrusion
• Difficult to cut Shape
• Delayed union or non-union of defect site
• Slow rate of Resorption
• Autograft
• Patient morbidity/Severe side effects
• Double operation required

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Competitor Analysis and Current Needs
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End-user Requirements

• Product must resorb in 9 - 12 months
• Must be wettable
• Good handling and shapability is a must
• Structurally sound and robust material
• Require no time limits in which the BGS is
  usable

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Technology
A polymer/glass-based fully resorpable scaffold
that promotes fast bone growth and is easy to cut
shape
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Overview

• Incorporation of glass improves or maintains
• Handlability (easy to cut shape)
• Porosity (70 80)
• Compression resistance
• Bone forming properties
• Ease of manufacture

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Mechanical Properties
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Corglaes 151 (Powder)
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Corglaes 101 (Powder)
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Corglaes 107 (Fibre, F2)
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In Vitro Testing
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Background- Osteoblast differentiation

• In vitro stem cells can be induced to
  differentiate into bone forming cells
  (osteoblasts), using a combination of chemicals
• Osteogenic media commonly contains
• Dexamethasone
• Beta glycerophosphate
• L ascorbic acid
• In vitro, these substances are capable of
  promoting gene expression, in a manner that
  results in osteogenesis.

Runx2 Collagen type I osteocalcin
Growth
Differentiation
MSC Osteoprogenitor
mature osteoblasts
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Experimental set up

• All experiments were carried out over 21 days and
  analysed at days 1,7,14 and 21.
• All experiments were carried out in 24 well
  plates and appropriate media replaced every 2
  days.
• Cells used were adipose derived mesenchymal stem
  cells, which have previously been shown to form
  osteoblasts within 21 days.

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Nomenclature

• NOR
• Cells cultured on tissue culture plastic without
  osteogenic media
• OS
• Cells cultured on tissue culture plastic with
  osteogenic media
• HA
• Cells cultured on commerical hydroxyapatite with
  osteogenic media
• BL
• Cells cultured on BLANK scaffolds with osteogenic
  media
• 5
• Cells cultured on scaffolds containing 5
  phosphate fibres with osteogenic media

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Viability live dead staining
BL
5
Green live cells (Calcein AM) Red dead cells
(propidium iodide )
CONTROL
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RUNX2 early osteogenic marker
Day 7
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COLLAGEN TYPE I -mid/early osteogenic protein
Day 14
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OSTEOCALCIN- late stage osteogenic protein
Day 14
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Gene expression
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Alkaline Phosphatase
Day 14
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Alizarin Red (Calcium)
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Von Kossa (Phosphate)
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Von Kossa (x10)
BL
5
HA
PL
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In Vivo Studies
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Stability Storage testing

• Accelerated ageing
• 40 C /75 RH for 130 days
• Further studies (GMP)
• Accelerated ageing at 25/60,30/75, 40/75
• Photostability
• Real time study (24 months)
• Materials will be tested at various time points

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Further work

• Accelerated ageing
• Full in vivo study (7 -9 months)
• Further In Vitro studies
• GMP Manufacturing
• Clinical trial
• Fund raising