Biohybrid for Osteochondral repair.

Lead Research Organisation: Imperial College London
Department Name: Materials

Abstract

The aim of the project is to design an osteochondral implant for localised repairs in the femoral condyle of the knee, delaying or preventing entirely the need for a total joint replacement. This implant will be 3D printed using silica/poly(tetrahydrofuran)/poly(epsilon-caprolactone) sol-gel hybrids, first synthesized and patented by Dr Francesca Tallia. Chondral implants are currently being developed
using this material. Extending the implants to be complete osteochondral devices would enable the
treatment of more injuries, affecting both cartilage and bone of the knee joint, as well as establishing
a good fixation of the implant to the subchondral bone. Some of the initial objectives of this PhD
include:
1- Optimising the synthesis of calcium sol-gel hybrids to 3D print bone scaffolds for the osteochondral implant.
2- Designing the overall osteochondral implant, taking into account the four main layers: a smooth disc, a cartilage scaffold, a dense boundary and a bone scaffold, all matching the mechanical and tribological properties of the host tissues.
3- Preparing for large animal studies for the chondral implant to investigate fixation and tribology of the device.
The design of the osteochondral scaffold implant requires knowledge on the gradients in mechanical
properties of the host tissues: the cartilage (chondral) and subchondral bone (osteo). Bone requires
larger pores and an interconnected network, due to the need for vascularisation, and is stiffer than
cartilage. Cartilage, however, has multiple layers (superficial, transitional and radial zones) and strain
gradients to consider when designing the implant. The current implant consists of a SiO2/PTHF PCL_diCOOH hybrid moulded disc, a few hundred microns thick with surface roughness similar to cartilage, bonded to a 3D printed porous scaffold of the same material. The disc and scaffold
need to be put in contact at the correct gelation time (4h) to bond together efficiently, creating a
strong interface. The aim is to extend this implant by adding a bone scaffold, which requires a different geometry of scaffold than for cartilage regeneration, with larger pores and interconnected channel size. This varying geometry will alter mechanical properties by increasing porosity volume percent of the scaffold. However, bone supports need a higher stiffness, therefore it may be necessary to test larger strut size to account for these design changes. Whilst the scaffold geometry itself will help to promote bone regeneration by guiding cells, a change in the hybrid composition might be necessary for the correct differentiation of cells. The addition of calcium and phosphate to the sol-gel hybrid could help with hydroxycarbonate apatite deposition and osteoblast proliferation. However, calcium incorporation to the network at low temperatures poses a challenge. With conventional calcium sources, such as calcium nitrate, toxic by-products need to be heated above 400C to be removed.
Hybrids' polymer component would degrade if heated to such temperatures. Calcium methoxyethoxide (CME) seems like the most promising route to incorporate calcium to the inorganic network at room temperature, previously investigated by Dr Hung Kai Tin. For this part of the project, the composition of the ink will be optimised to ensure the calcium doesn't prevent efficient 3D printing of the scaffolds, as well as keeping a similar inorganic/organic ratio to the original SiO2/PTHF/PCL_diCOOH hybrid. Once the calcium sol-gel synthesis has been optimised, the stiffness of the bone scaffolds will be studied using 3D printing techniques to increase the scaffold strut diameter and testing the scaffolds in compression. Once bone scaffolds are 3D printable with properties matching the subchondral bone plate, the bonding of the CME sol-gel and original sol-gel composition will be considered.
This leads into the second part of the project; working on designing the osteochondral implant.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R512540/1 01/10/2017 31/03/2022
2132090 Studentship EP/R512540/1 29/09/2018 31/03/2022 Agathe Heyraud