Bone healing is a dynamic process regulated by biochemical signals such as chemokines and growth factors, and biophysical signals such as topographical and mechanical features of extracellular matrix or mechanical stimuli. Hereby, a mechanically tough and bioactive hydrogel based on autologous injectable platelet‐rich fibrin (iPRF) modified with gelatin nanoparticles (GNPs) is developed. This composite hydrogel demonstrates a double network (DN) mechanism, wherein covalent network of fibrin serves to maintain material integrity, and self‐assembled colloidal network of GNPs dissipates force upon loading. A rabbit sinus augmentation model is used to investigate the bioactivity and osteogenesis capacity of the DN hydrogels. The DN hydrogels adapt to the local environmental complexity of bone defects, i.e., accommodate the irregular shape of the defects and withstand the pressure formed in the maxillary sinus during animal's respiration process. The DN hydrogel is also demonstrated to absorb and prolong the release of the bioactive growth factors stemming from iPRF, which could have contributed to the early angiogenesis and osteogenesis observed inside the sinus. This adaptable and bioactive DN hydrogel can achieve enhanced bone regeneration in treating complex bone defects by maintaining long‐term bone mass and withstanding the functional mechanical stimuli.
Risk of implant failure increases profoundly in patients with pre‐existing conditions (e.g., diabetes). Current therapies adopt a one‐sided focus on the direct antibacterial properties of biomaterials and osteogenesis stimulation. However, in this study it is demonstrated that a “chain armor” structure (Ce‐TA) that mainly targets the regulation of the local pathological microenvironment, provides a novel solution to scavenge reactive oxygen species (ROS) by simulating superoxide dismutase and catalase and significantly improving osteointegration under diabetic conditions. Ce‐TA based on a metal phenolic network biological functional interface is successfully constructed. Ce‐TA, an ultrathin armor structure, is biocompatible and facile. Through in vitro assays it is demonstrated that Ce‐TA reshapes the diabetic microenvironment into a regenerative one in a microenvironment‐responsive manner, where Ce‐TA regulates hypoxia‐inducible factor 1α (HIF‐1α) activity by reducing the level of mitochondrial ROS, and effectively alleviates mitochondrial dysfunction and reprogrammes macrophages to a pro‐healing state. Furthermore, it is confirmed that Ce‐TA shows excellent therapeutic effects on the reducing postoperative infection and enhances osteointegration of intra‐osseous implants in diabetic rat models. The proposed strategy opens up a promising opportunity for repurposing metals with intrinsic enzyme‐like activity for the goal of enhancing the osteointegration of devices with orthopedic and dental applications among diabetic patients.
Osteoporosis
is a wide-range disease with a negative impact on
bone defect healing. Strontium ranelate (SR) has promising osteogenic
potential for its dual function on stimulating osteoblasts and inhibiting
osteoclast activity. However, it has limitations for its dose-dependent
effect and side effects on systemic applications. Here, a sequentially
cross-linking strategy including enzyme-cross-linking through tyrosinase
from mushroom and physical folding is acquired to create SR loaded
gelatin nanoparticle/silk fibroin aerogel (abbreviated as S/G-Sr-MT)
with drug release controlling capacity. The results showed successful
enzyme-cross-linking, excellent spatial structure, and enhanced mechanical
properties of S/G-Sr-MT. Even Sr2+ loading and stable release
with markedly inhibited initial burst release were detected. The biomineralization
investigation showed rapid deposition of hydroxyapatite on the surface
of S/G-Sr-MT. In vitro, spreading morphology and higher osteogenic
gene expression of MC3T3-E1 seeded on S/G-Sr-MT were observed compared
to other groups after 7 day culturing. In vivo, S/G-Sr-MT showed an
obvious osteogenic capacity in calvaria defects of ovariectomized
rats in which high Runx2 expression and inhibited
TRAP activity were observed. Such results suggested the S/G-Sr-MT
scaffold could stimulate osteogenic differentiation of osteoblasts
while inhibiting osteoclast behaviors in vivo. These findings highlight
the potential osteogenic ability and clinical application of SR incorporated
enzyme-cross-linked scaffold in ovariectomized (OVX) bone healing.
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