Mineralized Enzyme-Based Biomaterials with Superior Bioactivities for Bone Regeneration

Abstract

The formation and metabolic balance of bone tissue is a controllable process of biomineralization, which is regulated by various cells, biomolecules, and ions. Enzyme molecules play an important role in this process, and alkaline phosphatase (ALP) is one of the most critical factors. In this study, inspired by the process of bone biomineralization, a biomimetic strategy is achieved for the preparation of mineralized ALP nanoparticles (MALPNs), by taking advantages of the unique reaction between ALP and calcium ions in Dulbecco's modified Eagle's medium. Benefiting from the mild biomineralization reaction, the MALPN system highly maintains the activity of ALP. Furthermore, the in vitro studies show that the MALPN system significantly enhances the proliferation of bone marrow mesenchymal stem cells and upregulates their osteogenic differentiation. When evaluated as synthetic graft materials for bone regeneration, the MALPN-incorporated gelatin methacryloyl graft shows excellent mechanical properties, a sustained release profile of ALP, and high biocompatibility and efficacy in guiding bone regeneration and vascularization for criticalsized rat calvarial defect. Moreover, we also demonstrate that the biomimetic mineralization strategy can be adopted for other proteins such as acid phosphatase, bovine serum albumin, fibrinogen, and gelatin, suggesting its universality for constructing mineralized protein-/enzyme-based bioactive materials for the application of tissue regeneration.

In Situ Enzymatic Reaction Generates Magnesium‐Based Mineralized Microspheres with Superior Bioactivity for Enhanced Bone Regeneration

“…[16] Alkaline phosphatase (ALP), a common enzyme involved in in vivo biomineralization, can cleave phosphate esters and increase the local concentration of inorganic phosphate ions (Pi) that are necessary for hard tissue biomineralization. [17,18] ALP has been used to develop hybrid scaffolds of calcium phosphate (CaP) and polymers for bone tissue regeneration. [19][20][21] Using this approach, the mineralization rate of polymer scaffolds can be effectively controlled, resulting in denser and more uniform CaP deposits on the matrix.…”

Micron/Submicron Scaled Hierarchical Ti Phosphate/Ti Oxide Hybrid Coating on 3D Printed Scaffolds for Improved Osteointegration

“…Some researchers suggested that osteointegration depends not only on the chemical composition of the implant surface but also on the microstructure of the surface . Various types of surface modifications such as material coating, surface protein grafting, and increasing surface roughness have been applied to improve the osteointegration of the implant surface and the surrounding bone. , The excellent performance of natural bone is due to its multicomponent and hierarchical hybrid structure . From a bionic point of view, a hierarchical surface topography of the implant would be more favorable for osteogenesis .…”

“…11,12 The excellent performance of natural bone is due to its multicomponent and hierarchical hybrid structure. 13 From a bionic point of view, a hierarchical surface topography of the implant would be more favorable for osteogenesis. 14 In our previous work, we have introduced a hydrothermal technique to fabricate Ti implants with phosphoric acid etching and a biomimetic hierarchical structure, which achieved upgraded performance in cell adhesion and early osteointegration.…”

Osteogenesis Enhancement with 3D Printed Gene-Activated Sodium Alginate Scaffolds

“…Biomimetic scaffolds, primarily based on biopolymers, such as collagen, hyaluronic acid, and alginates, not only provide a minimal adverse immune response and are available in virtually unlimited quantities, but may also possess desirable osteoinductive and osteoconductive properties for more efficient bone reconstruction [6,7]. The combination of osteoinductive growth factors and osteoconductive hydrogel scaffolds tends to meet the requirements for synthetic bone substitutes in full, providing protein bioactivity in the implantation zone, as well as a microenvironment for newly formed tissue [8,9]. Bone morphogenetic proteins (BMPs) are considered to be crucial biomolecules for stimulating and promoting osteogenic differentiation in cells [10,11].…”