Gelatin Nanoparticle‐Injectable Platelet‐Rich Fibrin Double Network Hydrogels with Local Adaptability and Bioactivity for Enhanced Osteogenesis

Abstract

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.

Histological and Histomorphometric Evaluation of Applying a Bioactive Advanced Platelet-Rich Fibrin to a Perforated Schneiderian Membrane in a Maxillary Sinus Elevation Model

“…Based on previous studies, there are two sources of osteogenesis in the elevated sinus floor area. One is osteogenesis from the basal bone, and the other is from the SM (Srouji et al, 2009;Mu et al, 2020). Figures 6B,C show that the osteogenic pattern of the CM originated solely from the basal bone.…”

“…All operations were performed under sterile conditions by one surgeon (Liangjing Xin). The 24 rabbits were subjected to the maxillary sinus floor elevation process as previously described (Mu et al, 2020). In detail, the rabbits were anesthetized using 30 mg/kg xylazine hydrochloride (Rompun; Bayer, Seoul, Korea).…”

“…Nevertheless, the dense structure of the CM might block the osteogenesis of the SM. The SM is a possible source of osteogenesis in the maxillary sinus (Srouji et al, 2009;Jung et al, 2015;Mu et al, 2020), and the implantation of an absorbable CM might slow new bone formation in the sinus cavity (Gruber et al, 2004;Palma et al, 2006). Although CMs have been widely used to repair SM perforation, it is not clear if the degradation and mechanical properties of the CM are compatible with the repair process.…”

<p>Nano-Silicate-Reinforced and SDF-1α-Loaded Gelatin-Methacryloyl Hydrogel for Bone Tissue Engineering</p>

“…[29][30][31] In particular, injectable osteogenic hydrogels have been attracting attention owing to their unique ability to fill irregular bone defects using minimally invasive procedures. [15][16][17] However, considering the complication of most synthetic processes, most fabrication strategies to date are time-consuming and expensive. [51][52][53] Although some stem cell-loaded hydrogels have demonstrated the capability to promote bone regeneration in animal models, 25,54,55 these strategies are affected by limited cell sources, low cell viability, or controversial therapeutic effects.…”

“…15 Injectable osteogenic hydrogels have been attracting considerable attention because of their ability to fill irregular bone defects using a minimally invasive procedure. 16,17 However, from a clinical perspective, the fabrication of an injectable hydrogel platform involving simple and rapid production possessing long-term osteogenic ability remains highly desirable.…”