Recent Trends in the Development of Bone Regenerative Biomaterials

Abstract

The goal of a biomaterial is to support the bone tissue regeneration process at the defect site and eventually degrade in situ and get replaced with the newly generated bone tissue. Biomaterials that enhance bone regeneration have a wealth of potential clinical applications from the treatment of non-union fractures to spinal fusion. The use of bone regenerative biomaterials from bioceramics and polymeric components to support bone cell and tissue growth is a longstanding area of interest. Recently, various forms of bone repair materials such as hydrogel, nanofiber scaffolds, and 3D printing composite scaffolds are emerging. Current challenges include the engineering of biomaterials that can match both the mechanical and biological context of bone tissue matrix and support the vascularization of large tissue constructs. Biomaterials with new levels of biofunctionality that attempt to recreate nanoscale topographical, biofactor, and gene delivery cues from the extracellular environment are emerging as interesting candidate bone regenerative biomaterials. This review has been sculptured around a case-by-case basis of current research that is being undertaken in the field of bone regeneration engineering. We will highlight the current progress in the development of physicochemical properties and applications of bone defect repair materials and their perspectives in bone regeneration.

Keywords: 3D printing; bone defect; regenerative biomaterials; tissue engineering; tissue scaffold.

FIGURE 1

Histologic slides of iliac (A) and tibial (B) bone graft. The iliac crest bone graft shows abundant osteoblasts and hematopoietic marrow. The tibial bone graft shows fatty marrow without hematopoiesis. Reproduced from Chiodo et al. (2010) with permission from SAGE (Copyright 2010).

FIGURE 2

Modified demineralized bone matrix with nanoscaled and multi-layered recombinant fibronectin/cadherin chimera for bone repair. Reproduced from Xing et al. (2017) with permission from Elsevier (Copyright 2017).

FIGURE 3

New bone formation within bone tunnel. (A) Representative radiographs at 4, 8, and 12 weeks after surgery. (B) Representative 3D micro-CT images within a region of interest of central 2.5 mm in diameter of the bone tunnel at 4, 8, and 12 weeks after surgery. (C) Quantitative analysis of micro-CT of the new bone in the bone tunnel at 4, 8, and 12 weeks after surgery: (C1) BV; (C2) BV/TV; (C3) Tb.N; (C4) BMD; (C5) Tb. Sp. n = 8. *p < 0.05 vs. control group, **p < 0.01 vs. control group, ***p < 0.001 vs. control group, ^#p < 0.05 vs. PT group, ^##p < 0.01 vs. PT group. Reproduced from Lai et al. (2019) with permission from Elsevier (Copyright 2019).

FIGURE 4

Diagram of the formation mechanism of porous HA/rGO composite scaffold. Reproduced from Zhou et al. (2019) with permission from the American Chemical Society (Copyright 2019).

FIGURE 5

Hard tissue section stained by van Gieson staining (A) and histomorphometric analysis (B) of Ti6Al4V and Ta scaffolds at 4, 8, and 12 weeks after surgery. The red-stained tissue represents bone tissue; at 4 weeks, the amount of new bone tissue in the scaffolds is thin and irregular. Osteoblasts seam with bone-lining cells, indicating active bone formation. *P < 0.05, vs. Ti6Al4V group. (C) SEM images of bone apposition and bone microstructure on porous scaffolds at di?erent positions at 4, 6, and 12 weeks. White: implant; gray: new bone. Reproduced from Guo et al. (2019) with permission from the American Chemical Society (Copyright 2019).

FIGURE 6

(A,B) Molecular structures and self-assembling properties of peptide gelator and SF for the formation of nanofiber and nanofibril bundle structures. (C) Schematic of preparation process of SF-RGD for bone regeneration in calvarial defect areas of mouse. Reproduced from Yan et al. (2018) with permission from Wiley (Copyright 2018).

FIGURE 7

Schematic diagram of calcium phosphate-based composite cement with an embedded 3D plotted PLGA network and bioactive wollastonite for osteogenesis and angiogenesis. Reproduced from Qian et al. (2019) with permission from Wiley (Copyright 2019).

FIGURE 8

(A) Formation of the polymer network from HEMA and DMAEDA via Michael addition reaction (purple arrows: positive charges of DMAEMA). (B) In situ self-assembly of CaP NPs around -COOH group of PGA via -COO^– -Ca²⁺ coordination. (C) The interaction between the PGA and the polymer network via electrostatic attraction. Reproduced from ref. Kuang et al. (2019) with permission from the American Chemical Society (Copyright 2019).

FIGURE 9

Strategy for fabrication of MANF hydrogels from gelatin nanofibrous microparticles. Reproduced from Hou et al. (2019) with permission from Elsevier (Copyright 2019).

FIGURE 10

siRNA-decorated nanoparticles were assembled to engineer a hierarchical nanostructured coating on clinically used titanium implants for the synergistic regeneration of skeletal and vascular tissues. Reproduced from Xing et al. (2020) with permission from Elsevier (Copyright 2020).