Growth factor delivery
using acellular matrices presents a promising
alternative to current treatment options for bone repair in critical-size
injuries. However, supra-physiological doses of the factors can introduce
safety concerns that must be alleviated, mainly by sustaining delivery
of smaller doses using the matrix as a depot. We developed an acellular,
biodegradable hydrogel implant composed of poly(ethylene glycol) (PEG)
and denatured albumin to be used for sustained delivery of bone morphogenic
protein-2 (BMP2). In this study, poly(ethylene glycol)–albumin
(PEG-Alb) hydrogels were produced and loaded with 7.7 μg/mL
of recombinant human BMP2 (rhBMP2) to be tested for safety and performance
in a critical-size long-bone defect, using a rodent model. The hydrogels
were formed ex situ in a 5 mm long cylindrical mold of 3 mm diameter,
implanted into defects made in the tibia of Sprague–Dawley
rats and compared to non-rhBMP2 control hydrogels at 13 weeks following
surgery. The hydrogels were also compared to the more established
PEG–fibrinogen (PEG-Fib) hydrogels we have tested previously.
Comprehensive in vitro characterization as well as in vivo assessments
that include: histological analyses, including safety parameters (i.e.,
local tolerance and toxicity), assessment of implant degradation,
bone formation, as well as repair tissue density using quantitative
microCT analysis were performed. The in vitro assessments demonstrated
similarities between the mechanical and release properties of the
PEG-Alb hydrogels to those of the PEG-Fib hydrogels. Safety analysis
presented good local tolerance in the bone defects and no signs of
toxicity. A significantly larger amount of bone was detected at 13
weeks in the rhBMP2-treated defects as compared to non-rhBMP2 defects.
However, no significant differences were noted in bone formation at
13 weeks when comparing the PEG-Alb-treated defects to PEG-Fib-treated
defects (with or without BMP2). The study concludes that hydrogel
scaffolds made from PEG-Alb containing 7.7 μg/mL of rhBMP2 are
effective in accelerating the bridging of boney defects in the tibia.
Treatment of peripheral nerve injuries has evolved over the past several decades to include the use of sophisticated new materials endowed with trophic and topographical cues that are essential for in vivo nerve fibre regeneration. In this research, we explored the use of an advanced design strategy for peripheral nerve repair, using biological and semi-synthetic hydrogels that enable controlled environmental stimuli to regenerate neurons and glial cells in a rat sciatic nerve resection model. The provisional nerve growth conduits were composed of either natural fibrin or adducts of synthetic polyethylene glycol and fibrinogen or gelatin. A photo-patterning technique was further applied to these 3D hydrogel biomaterials, in the form of laser-ablated microchannels, to provide contact guidance for unidirectional growth following sciatic nerve injury. We tested the regeneration capacity of subcritical nerve gap injuries in rats treated with photo-patterned materials and compared these with injuries treated with unpatterned hydrogels, either stiff or compliant. Among the factors tested were shear modulus, biological composition, and micropatterning of the materials. The microchannel guidance patterns, combined with appropriately matched degradation and stiffness properties of the material, proved most essential for the uniform tissue propagation during the nerve regeneration process.
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