Tough, Injectable Calcium Phosphate Cement Based Composite Hydrogels to Promote Osteogenesis

Abstract

Osteoporosis is one of the most disabling consequences of aging, and osteoporotic fractures and a higher risk of subsequent fractures lead to substantial disability and deaths, indicating that both local fracture healing and early anti-osteoporosis therapy are of great significance. However, combining simple clinically approved materials to achieve good injection and subsequent molding and provide good mechanical support remains a challenge. To meet this challenge, bioinspired by natural bone components, we develop appropriate interactions between inorganic biological scaffolds and organic osteogenic molecules, achieving a tough hydrogel that is both firmly loaded with calcium phosphate cement (CPC) and injectable. Here, the inorganic component CPC composed of biomimetic bone composition and the organic precursor, incorporating gelatin methacryloyl (GelMA) and N-Hydroxyethyl acrylamide (HEAA), endow the system with fast polymerization and crosslinking through ultraviolet (UV) photo-initiation. The GelMA-poly (N-Hydroxyethyl acrylamide) (GelMA-PHEAA) chemical and physical network formed in situ enhances the mechanical performances and maintains the bioactive characteristics of CPC. This tough biomimetic hydrogel combined with bioactive CPC is a new promising candidate for a commercial clinical material to help patients to survive osteoporotic fracture.

Unveiling the versatility of gelatin methacryloyl hydrogels: a comprehensive journey into biomedical applications

“…researchers have investigated GelMA-based hydrogel scaffolds for BTE. For example, Osteogenic growth peptide-incorporated GelMA/HAMA hydrogel [121], Strontiumsubstituted hydroxyapatite/Teriparatide-loaded GelMA/double bonded heparin hydrogel [122], Lithium chloride-loaded GelMA/Sodium alginate (SA) hydrogel [123], Silver-doped Hydroxyapatite microspheres loaded in GelMA hydrogel [124], GelMA/dopamine methacrylate-polydopamine hydrogel coating on phthalazinone-based poly (aryl ether nitrile ketone) [125], calcium phosphate cement/GelMA-poly (N-Hydroxyethyl acrylamide) [126]. GelMA/GO [127], GelMA/dendrimer (G3)functionalized nanoceria [128], rBMSCs-loaded GelMA/alginate hydrogel microspheres incorporated with naringin [129], platelet-derived growth factor-BB (PDGF-BB) loaded GelMA/Laponite ® [130], Zirconia-incorporated GelMA/alginate [131], miR-26a-integrated exos/GelMA-Chitosan-methyl methacrylate [132], anti-CXCL9-loaded and OP3-4 incorporated GelMA [133] have shown promising results in BTE.…”

Lubricating Polymer Gels/Coatings: Syntheses and Measurement Strategies

“…By using light as the trigger for polymerization, this method offers advantages such as precise control over the reaction, the ability to initiate polymerization in specific regions or patterns, low energy consumption, and wide adaptability over thermal polymerization [ 49 , 50 ]. Through this method, a vertical and horizontal dual gradient hydrogel-filled anisotropic tubular polymer skeleton (COF ≈ 0.0036) [ 51 ], hydrogel–elastomer hybrid surface [ 52 ], and GelMA-poly (N-Hydroxyethyl acrylamide) (GelMAPHEAA) chemical and physical network [ 53 ] were constructed.…”

Calcium Orthophosphate (CaPO4) Containing Composites for Biomedical Applications: Formulations, Properties, and Applications

“…Therefore, several attempts have been made to transform them into biocomposites to improve their properties, for example, by adding PEG [479,480], polylactide [481], PLGA [482], gelatin [414,[483][484][485][486], osteocalcin/collagen [487], alginic acid [488], chitin [489], chitosan [451,490], fibrin glue [491], silk fibroin [492,493], silanized HPMC [494], CMC [495], PVA fibers with CMC [496] and without CMC [497], CMC/gelatin/fullerenol [498], bioactive glass [499][500][501][502], bioactive glass functionalized with hypoxia conditioned medium [503], calcium silicate [504][505][506], cockle shell powders [507], metals [508], magnetic nanoparticles [509], and so on. Light-curing formulations have also been prepared [510,511]. Furthermore, a wide range of reinforcing additives with varying forms and characteristics are frequently employed to enhance the mechanical characteristics of CaPO 4 compositions that self-harden [512,513].…”

“…It is believed that biocomposites composed of CaPO 4 and different kinds of resins have mechanical and biological characteristics similar to those of ordinary PMMA cement and can be used for implant fixation [228,229,[531][532][533]. To enhance the mechanical characteristics of self-hardening CaPO 4 -based formulations and maintain stability at the implant site, numerous researchers have turned to in situ curing formulations, mostly via polymer matrix crosslinking processes [511,[534][535][536][537]. For instance, crosslinked CDHA/calcium polyacrylate biocomposites were created when TTCP and PAA interacted [534].…”