Self assembling peptide (SAP) biomimetic scaffolds and hydroxyapatite
nanoparticles for skeletal and dental tissue repair:
Supervisory team: Prof J Kirkham (Principle Supervisor), Prof DJ Wood., Dept
of Oral Biology; Leeds Dental Institute University of Leeds and Dr A Aggeli, Dept
Chemistry, University of Leeds.
Background: The generation / replacement of mineralised tissue is a major clinical
need. The extracellular matrices of the skeletal tissues comprise of hydroxyapatite
mineral crystals embedded within and around an organic scaffold. We are using selfassembling peptides (SAPs) in a biomimetic strategy for skeletal tissue replacement
and repair. We have previously shown that rationally designed SAPs which
spontaneously form 3D fibrillar scaffolds in response to specific environmental
triggers may potentially be used as injectable biomaterials in skeletal tissue
engineering, including the treatment / prevention of dental caries (decay) and repair
of critical bone defects (Kirkham et al (2007) Journal of Dental Research, 86, pp.426430; Firth et al (2006) Nanomedicine, 1, pp.189-199). We have also developed
manufacturing processes to generate hydroxyapatite nanoparticles capable of
blocking the micropores that result in tooth sensitivity and providing crystal nuclei for
mineralised tissue regeneration.
Aim: The aim of this project is to combine SAP technology with delivery of
hydroxyapatite nanoparticles (“nano-HA”) to provide seeded scaffolds for use in rapid
repair of dental tissues and craniofacial defects, including alveolar ridge
augmentation and implant osseointegration.
Methods: The ability of different SAPs ± nano-HA to promote nucleation and support
the growth of hydroxyapatite mineral will be quantitatively determined in vitro using a
steady state nucleation assay. The resulting mineral deposits will be further
characterized using scanning electron microscopy (SEM) and transmission electron
microscopy (TEM) coupled with elemental analysis and electron diffraction. Best
candidate SAPs / nano-HA will be further screened in vitro to determine their
biocompatibility and osteoinductive capacity with adult stem cells derived from
human bone marrow or dental pulp. Cells will be analysed via conventional end-point
phenotype analysis for osteogenic markers, using immunohistochemistry,
histochemical staining, light, confocal and scanning electron microscopy and QRTPCR. In situ screening of SAP/nano-HA ability to occlude the pores in dentine and
tooth enamel will be assessed using SEM and scanning confocal laser microscopy.
Outcome: The long term research outcomes from the project will include 1)
development of novel functional injectable
scaffolds for bone
repair and
regeneration; and 2) identification of candidate SAP/nano-HA combinations for oral
healthcare applications including tooth sensitivity and “Filling without Drilling”.