Subproject for 3-D printed hyperelastic bone composites for bone regeneration and spine fusion

  • Shah, Ramille Nirav, (Subproject PI)
  • Hsu, Erin L (PD/PI)

Project: Research project

Description

Project Summary/Abstract
The goal of this research is to transform clinical care for patients with degenerative and traumatic bone
pathologies.
Despite recent advances in bone graft technology, a major void remains for orthopaedic surgeons who perform procedures that require bone healing [1]
. Current biologics on the market, such as recombinant
human bone morphogenetic protein -2 (rhBMP-2; INFUSE™), are effective but are associated with safety concerns; while
ceramics and demineralized bone matrices (DBM) are insufficiently effective for spine fusion.
Our goal is to develop an exogenous growth factor -
free ceramic composite scaffold that is safe, easy to
manipulate, and more effective at inducing bone formation
and spine fusion relative to currently available
products.
To this end, our group has developed a unique 3D-
printable hydroxyapatite (HA) ink that can be used to create
a robust composite scaffold that not only promotes bone regeneration
, but also has hyperelastic mechanical properties that improves functionality and delivery in both open and minimally in
vasive spine fusion procedures.

This 3D -printed technology is easily scalable and facilitates incorporation of other bioactive factors or drugs, since ink synthesis ,
3D -printing , and processing are carried out at ambient emperatures.
In preliminary work, we developed a strategy to
3D-print a variation on this hyperelastic HA (hHA) that
incorporates demineralized bone matrix (DBM) particles into the 3D -ink, which imparts an added
osteoinductive stimulus from the native bioactive growth factors present
with in the DBM. The result is a flexible and elastic hHA -
DBM composite that we believe is the basis for a highly effective bone graft substitute for both open and minimally invasive spine fusion procedures.
With this proposal, we will 1)develop the optimal 3D -ink
formulation and printing parameters and evaluate the capacity of this hyperelastic bone composite (HBC) to elicit spine fu
sion in a rat arthrodesis model; 2)compare its
efficacy (bone regenerative and spine fusion
capacities) directly with an established positive control (rhBMP
-
2; INFUSE™); and 3) compare the mechanisms of pro-
osteogenic action and inflammatory host response of the hyperelastic bone composite with that of rhBMP-2. We hypothesize that the resulting HBC will elicit comparable fusion rates and regenerative capacity to rhBMP -2, but will provoke a significantly lower inflammatory host response in the rat. This translational study aims to develop a technology that could modernize clinical care approaches , while advancing our understanding of the behavior and functionality of complex 3D-printed particle - based composites. Not only would this investigation lay the groundwork for a safe, efficacious , and cost effective therapy for spinal arthrodesis, but the versatility of design and rapid rate of manufacturing would also allow for efficient customizability to individual patients. We expect that full development of this technology would transform clinical practice for
patients with degenerative and traumatic conditions of the spine,
and would ultimately translate to other orthopaedic and non-orthopaedic settings where bone regeneration is required.
StatusActive
Effective start/end date4/1/162/29/20

Funding

  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (1R01AR069580-01)

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Bone Regeneration
Spine
Bone and Bones
Ink
Bone Matrix
Technology
Arthrodesis
Ceramics
Intercellular Signaling Peptides and Proteins
Transplants
Bone Substitutes
Printing
Durapatite
Biological Products
Orthopedics
Patient Care
Pathology
Safety
Costs and Cost Analysis
Research