Bioinspired Hydrogel Anchoring 3DP GelMA/HAp Scaffolds Accelerates Bone Reconstruction

Abstract

Seeking high biological activity and osteoinductive ability has always been an urgent problem for three-dimensional-printed (3DP) bony implants. Here, a 3DP methacrylic anhydride-modified gelatin (GelMA)/ hydroxyapatite (HAp) scaffold with a high solid content of 82.5% was prepared and anchored by a functionalized polyphenol hydrogel. The scaffold and hydrogel were organically integrated into a bioinspired bony implant (HGH) by phenolic hydroxyl of hyaluronan derivatives conjugating amino groups of collagen I and GelMA and further chelating calcium ions of HAp. Compared with a simplex 3DP scaffold, this freeze-dried HGH presented better water retention, delayed degradation, and mechanical stability. It could promote migration, proliferation, and osteogenic differentiation of bone marrow stem cells in vitro. One week of implantation showed that it promoted directional migration of endogenous stem cells and early osteogenesis and angiogenesis. After 15 week surgery of rabbit skull defects, the BV/TV value of HGH returned to 73% of the normal group level. This strategy provided a new research idea for bone regeneration.

Progress in Gelatin as Biomaterial for Tissue Engineering

“…As mentioned above, 3D printing has paved the way towards clinical use by designing high-precision and sophisticated systems, alongside high cost-effectiveness. Since gelatin is able to crosslink in situ as well as to provide biologically suitable properties (ability to promote cell adhesion, proliferation and differentiation), gelatin-based inks or its derivatives (for instance, GelMA) have been extensively exploited in several tissues such as bone, skin and cornea [107][108][109][110].…”

“…The high content of an inorganic component demonstrated good printability and improved the mechanical properties of the natural polymer, obtaining high rates of osteoconductivity. The printable hydrogel, in comparison to empty scaffolds, also prolonged degradation time and demonstrated its ability to promote cell adhesion, proliferation and differentiation in vitro as well as to regenerate bone tissue in vivo by attracting endogenous stem cells and creating vascular constructs [108]. Gelatin-derived ink also permits the integration of patient-derived stimulating compounds such as platelet-rich plasma or platelet-rich growth factors [109,111].…”

Gelatin Methacryloyl Hydrogels for Musculoskeletal Tissue Regeneration

“…The chemical similarity between hydroxyapatite and the mineral component of bone has made hydroxyapatite and/or calcium phosphate nanostructures one of the most extensively investigated nanocomposites. Several reports have demonstrated a degree of mechanical reinforcement of the otherwise soft hydrogel along with improved osteogenic differentiation of bone-precursor cells indicating improved bioactivity both in vitro [ 55 , 56 ] and in vivo [ 55 , 57 , 58 ]. Another study investigated the effect of incorporating biomimetically coated hydroxyapatite nanofibers (HANFs) with ultrahigh aspect ratio within GelMA and reported that the incorporation of 1.5 wt% of these nanostructures (15m-HANFs/GelMA) produced the best bone regeneration in vivo.…”

Modularized bioceramic scaffold/hydrogel membrane hierarchical architecture beneficial for periodontal tissue regeneration in dogs

“…Si-HPMC is a self-setting hydrogel with a variety of biomedical applications, such as the barrier in periodontal regeneration to Scheme 1 Schematic illustration for design and fabrication of organic-inorganic biphasic hierarchical architecture for guided tissue regeneration therapy prevent cell invasion [26,27]. In order to accelerate the crosslinking process of Si-HPMC, a mixture composed of Si-HPMC and GelMA was prepared because the latter is a gelatin-derived biomaterial with good photo-crosslinking ability [28][29][30]. Also, GelMA may tune an appropriate curing time for the mixture of GelMA/Si-HPMC and optimize the mechanical and biodegradable properties of the hydrogel membranes simultaneously.…”