The current study has investigated the use of decellularised, demineralised bone extracellular
matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation.
Stro-1-enriched human bone marrow stromal cells were incorporated together with select
growth factors including VEGF, TGF-β3, BMP-2, PTHrP and VitD3, to augment bone formation,
and mixed with alginate for structural support. Growth factors were delivered through
fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles.
Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue
assessed by micro-CT correlated with histologically assessed mineralised bone formation
in all constructs. Exogenous growth factor addition did not enhance bone formation further
compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone
formation through degradation of intrinsic growth factors within the bone ECM component
and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/
ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic
growth factors led to altered bone formation. All constructs demonstrated extensive host tissue
invasion and vascularisation aiding integration and implant longevity. The proposed
hydrogel system functioned without the need for growth factor incorporation or an exogenous
inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch
variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile
biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately,
to form the tissue of choice through incorporation of select growth factors.