1 research outputs found
Polysaccharide-Based Composite Hydrogel with Hierarchical Microstructure for Enhanced Vascularization and Skull Regeneration
Critical-size skull defects caused by trauma, infection,
and tumor
resection raise great demands for efficient bone substitutes. Herein,
a hybrid cross-linked hierarchical microporous hydrogel scaffold (PHCLS)
was successfully assembled by a multistep procedure, which involved
(i) the preparation of poly(lactic-co-glycolic)/nanohydroxyapatite
(PLGA-HAP) porous microspheres, (ii) embedding the spheres in a solution
of dopamine-modified hyaluronic acid and collagen I (Col I) and cross-linking
via dopamine polyphenols binding to (i) Col I amino groups (via Michael
addition) and (ii) PLGA-HAP (via calcium ion chelation). The introduction
of PLGA-HAP not only improved the diversity of pore size and pore
communication inside the matrix but also greatly enhanced the compressive
strength (5.24-fold, 77.5 kPa) and degradation properties to construct
a more stable mechanical structure. In particular, the PHCLS (200
mg, nHAP) promoted the proliferation, infiltration, and angiogenic
differentiation of bone marrow mesenchymal stem cells in vitro, as
well as significant ectopic angiogenesis and mineralization with a
storage modulus enhancement of 2.5-fold after 30 days. Meanwhile,
the appropriate matrix microenvironment initiated angiogenesis and
early osteogenesis by accelerating endogenous stem cell recruitment
in situ. Together, the PHCLS allowed substantial skull reconstruction
in the rabbit cranial defect model, achieving 85.2% breaking load
strength and 84.5% bone volume fractions in comparison to the natural
cranium, 12 weeks after implantation. Overall, this study reveals
that the hierarchical microporous hydrogel scaffold provides a promising
strategy for skull defect treatment