Overcoming the Limitations of Allograft in Impaction Bone Grafting for Revision Arthroplasty

Lead Research Organisation: University of Southampton
Department Name: Development Origin of Health and Disease

Abstract

The replacement of lost bone is a major clinical and socio-economic need, particularly in the fields of revision arthroplasty, spinal and trauma surgery. Often, a lack of sufficient host (own or autogenous) bone precludes the universal use of autogenous bone while the use of donor (allogeneic) bone carries risks of rejection and infection. Bone marrow contains stem cells (skeletal stem cells), which can be isolated and can be readily expanded, while retaining their ability to form a variety of tissues like bone and fat.

Given the demographic challenge of an ageing population, the development of strategies to exploit the potential of bone progenitors which can give rise to cells of the osteogenic lineage, offers a compelling approach to augment bone formation to replace or restore the function of traumatised or degenerated bone.

We propose a unique programme to create a living composite of bone progenitor cells and a synthetic scaffold together with a new innovative process for placing the synthetic polymer scaffold and cells in the hip cavity ( a process of vibration impaction bone grafting)that can be applied in orthopaedic applications requiring new bone stock. We will show in this work the ability of bone progenitor cells together with an optimised synthetic scaffold and an innovative vibration impaction process our ability to augment bone formation in impaction bone grafting. To prove our concept, we will use a standard clinical orthopaedic procedure called femoral impaction grafting wherein a new prosthesis is needed to replace a degenerated hip implant and needs bone stock.

Technical Summary

Each year in the UK there are over 50,000 primary hip replacement operations at a cost of #250million. With an increasing ageing population, this is set to rise to 65,000 by 2026 of which 30-50% will require subsequent revision surgery. In a large proportion, bone augmentation will be necessary. We have recently demonstrated the stimulation of new bone formation in a small animal in vivo model of impaction bone grafting. We proved that highly porous polymer scaffolds could mechanically shield skeletal or mesenchymal stem cells (MSCs) during impaction. After impaction the MSCs stimulated angiogenesis and augmented new bone formation. In parallel we have been developing protocols to improve the compaction process using vibration compaction strategies as the risk of femoral fracture in impaction bone grafting of the femur is substantial. Our approach can be used to extend or replace auto and allograft in revision hip arthroplasty. We require funding to transfer the concept of an allograft synthetic bone extender and vibration impaction processes to a larger clinically releavant ovine model of hip revision arthroplasty as a precursor for clinical trials.

Publications

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Aarvold A (2013) A tissue engineering strategy for the treatment of avascular necrosis of the femoral head. in The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and Ireland

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Aarvold A (2014) From bench to clinic and back: skeletal stem cells and impaction bone grafting for regeneration of bone defects. in Journal of tissue engineering and regenerative medicine

 
Title Computer tomopgraphy (uCT) 
Description ? New methodology (uCT) developed to analyse changes in bone structure after a short period of time such as the one experienced after the CAM assay 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact ? New methodology (uCT) developed to analyse changes in bone structure - improved data analysis across research spectrum 
 
Description In vivo collaborator 
Organisation Royal Veterinary College (RVC)
Department Veterinary Basic Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Training of Research Fellow by Professor Goodship and RVC Team
Collaborator Contribution Training and expertise in in vivo biology for tean and conduction of an in vivo ovine study
Impact Outputs too early from in vivo study - Multidisciplinary study involving in vivo, computer tomography, histology, mechanical analysis
Start Year 2011
 
Title Polymer Composite Material 
Description New material for use with skeletal cells in bone applications, in particualr impaction bone grafting 
IP Reference EP2385105 
Protection Patent application published
Year Protection Granted 2011
Licensed No
Impact None to date- only filed in Julyy 2011 -
 
Description Invited Speaker: Hungarian Academy of Sciences, Budapest 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave talk on "Harnessing Clay for Growth Factor, BMP-2, Delivery for Orthopaedics"
Year(s) Of Engagement Activity 2018
 
Description Invited speaker - 2018 Croucher Program, The Chinese University of Hong Kong, Shatin, Hong Kong. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited speaker - 2018 Croucher Program - Stem Cells Biology and Regenerative Medicine -Location (Site): Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.
Lecture 1: New approaches to skeletal cell based bone regeneration: repair, restore and recreate
Lecture 2: Harnessing ex vivo and in vivo models to interrogate and validate bone formation strategies
Lecture 3: Understanding anabolic and catabolic gene regulation in osteoarthritis
Year(s) Of Engagement Activity 2018
URL http://www.ort.cuhk.edu.hk/csc2018/index.html
 
Description LifeLab - School Interaction 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Poster Presentation
Geographic Reach Regional
Primary Audience Schools
Results and Impact Several schools involved in learninig about health, nutrition and disease risk - up to 100 Children involved

Schools interested in continuing the programme
Year(s) Of Engagement Activity 2011,2013
 
Description Open Conference "Stem cells for bone regeneration: state-of-the-art research and solutions" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Speaker - Bonebank Conference, Odense, Denmark. "Skeletal stem cells for bone tissue regeneration.".
The audience were peer scientists, clinicians and industrialist to inform, educate and debate developments in translational bone research.
Year(s) Of Engagement Activity 2016
 
Description Scientific Committee & Invited Speaker at European Orthopaedic Research Society (EORS) 2018 in Galway, Ireland 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Gave talk on "Skeletal Cell Based Strategies for Bone Repair - Opportunities and Challenges"
Year(s) Of Engagement Activity 2018
 
Description Speaker at UKRMP Conference UK 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Speaker - Inaugural UK Regenerative Medicine Conference, London. "Size matters - Harnessing biomimetic materials for skeletal tissue engineering."
The audience were peer scientists, clinicians and industrialist to inform, educate and debate developments in translational bone research.
Year(s) Of Engagement Activity 2016
 
Description Stem Cell Mountain at Bestival Music Festival Science Tent 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Stem Cell Mountain at the Bestival Music Festival Science Tent (4 days) - exhibit in shared Science Tent, mixed Festival audience (mainly general public and especially young people 17-25) Measure 1: visitors passing stand; 1400 per day = 5600 Measure 2: visitors interacting with researchers on stand; 500 per day = 2000 Particularly notable was the impact of this activity on the researchers themselves and how they viewed the importance of their own research. For example one researcher reported: "This festival was great to see how amazed people are about the potential of stem cells"
Year(s) Of Engagement Activity 2015
 
Description Winchester Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Stem Cell Mountain at a three day up and coming science festival. Engaged largely family audience and science festival talk attendees Measure 1: visitors passing stand; 300 per day = 900 Measure 2: visitors interacting with researchers on stand; 150 per day = 450
Year(s) Of Engagement Activity 2015