Materials evolution of bone plates for internal fixation of bone fractures: A review

doi:10.1016/j.jmst.2019.07.024

Abstract

Abstract:

Bone plates play a vital role in bone fracture healing by providing the necessary mechanical fixation for fracture fragments through modulating biomechanical microenvironment adjacent to the fracture site. Good treatment effect has been achieved for fixation of bone fracture with conventional bone plates, which are made of stainless steel or titanium alloy. However, several limitations still exist with traditional bone plates including loosening and stress shielding due to significant difference in modulus between metal material and bone tissue that impairs optimal fracture healing. Additionally, due to demographic changes and non-physiological loading, the population suffering from refractory fractures, such as osteoporosis fractures and comminuted fractures, is increasing, which imposes a big challenge to traditional bone plates developed for normal bone fracture repair. Therefore, optimal fracture treatment with adequate fixation implants in terms of materials and design relevant to special conditions is desirable. In this review, the complex physiological process of bone healing is introduced, followed by reviewing the development of implant design and biomaterials for bone plates. Finally, we discuss recent development of hybrid bone plates that contains bioactive elements or factors for fracture healing enhancement as a promising direction. This includes biodegradable Mg-based alloy used for designing bone screw-plates that has been proven to be beneficial for fracture healing, an innovative development that attracts more and more attention. This paper also indicates that the tantalum bone plates with porous structure are also emerging as a new fracture internal fixation implants. The reduction of the stress shielding is verified to be useful to accelerate bone fracture healing. Potential application of biodegradable metals may also avoid a second operation for implant removal. Further developments in biometals and their design for orthopedic bone plates are expected to improve the treatment of bone fracture, especially the refractory fractures.

Key words: Bone plate, Biomaterials, Biodegradable materials, Titanium, Magnesium, Porous tantalum

Junlei Li, Ling Qin, Ke Yang, Zhijie Ma, Yongxuan Wang, Liangliang Cheng, Dewei Zhao. Materials evolution of bone plates for internal fixation of bone fractures: A review[J]. J. Mater. Sci. Technol., 2020, 36: 190-208.

Figures/Tables 23

Fig. 1. Biological events of closed femur fracture healing for a mouse, and the cell types are involved at each stage of fracture healing. Abbreviations: PMN, polymorphonuclear leucocyte. Reprinted from Ref. [6] with permission.

Fig. 2. Mechanotransduction converts mechanical stimuli into chemical signals to regulate cell behavior and function. Reprinted from Ref. [11] with permission.

Fig. 3. Common medical devices used for fracture internal fixation. (a) Bone plate used for the fixation of ulnar fracture ; (b) Intramedullary nail used for the fixation of tibial fracture; (c) K-wire used for the fixation of phalangeal fracture; (d) Screws used for the fixation of femoral neck fracture.

Table 1 Different fracture sites using different internal fixation methods [22].

Fracture sites		Internal fixators
Head	Skull fracture Craniofacial fracture	Wires, pins and plates Wires, screws and plates
Trunk	Clavicle fracture Scapular fracture Pelvic fracture Spinal fracture	Intramedullary nail and plates Screws and plates Screws, plates and external fixators Fixation device consists of rods, pedicle screws and plates
Upper limb fracture	Humeral fracture Radius, ulnar fracture Metacarpal and phalangeal fracture	Open reduction with plate and screws/close reduction with intramedullary nail Open reduction with plate and screws/close reduction with intramedullary nail Close reduction with external fixators, open reduction with intramedullary nail, screws and plates
Lower limb fracture	Femoral fracture Tibial and fibular fracture Metatarsus fracture Calcaneal fracture	Open reduction with plate and screws/close reduction with intramedullary nail Open reduction with plate and screws and intramedullary nail Open reduction with plate and screws and intramedullary nail Close reduction and fixation with screws or wires

Fig. 4. Bone plates design of (a) Coapteur plate, (b) Tensioner plate, (c) Dynamic compression plate (DCP). Reprinted from Ref. [41] with permission.

Fig. 5. Mechanical properties of cortical bone and materials for orthopaedic implants.

Table 2 Compositions (wt%) of 316L stainless steel (ASTM F138) and variants [68].

ASTM code/UNS No of stainless steels	Cr	Ni	Mo	Mn	Si	Cu	N	C	P	S
F138/S31673	17.00-19.00	13.00-15.00	2.25-3.00	2.00	0.75	0.50	0.10	0.030	0.025	0.010
F1314/S20910	20.50-23.50	11.50-13.50	4.00-6.00	2.00-3.00	0.75	0.50	0.20-0.40	0.030	0.025	0.010
F1586/S31675 (Orthinox)	19.50-22.00	9.00-11.00	2.00-4.25	2.00-3.00	0.75	0.25	0.25-0.50	0.08	0.025	0.010
F2229/S29108	19.00-23.00	0.10	21.00-24.00	0.50-1.50	0.75	0.25	>0.90	0.08	0.03	0.010

Table 3 Mechanical properties of 316L stainless steel [79].

Young’s modulus (GPa)	Ultimate tensile strength (MPa)	Fatigue strength (MPa, 107 cycles)
193	540-1000	240-480

Fig. 6. 316L stainless steel bone plates used for (a) humeral fracture and (b) tibial fracture.

Table 4 Mechanical properties of titanium and titanium alloys used as bone plate materials [68,80,81].

Material	Standard	Modulus (GPa)	Tensile strength (MPa)	Alloy type	Smooth fatigue limit at 10⁷ cycles (MPa)	Notch fatigue limit at 10⁷ cycles (MPa)
First generation Ti-based medical metallic material (1950-1990)
Commercially pure Ti	ASTM 1341	110	240-550	α	88-413
Ti-6Al-4V ELI wrought	ASTM F136	110	860-965	α + β	500	290
Ti-6Al-4V ELI Standard grade	ASTM F1472	112	895-930	α + β
Ti-6Al-7Nb Wrought	ASTM F1295	110	900-1050	α + β	500-600
Ti-5Al-2.5Fe	-	110	1020	α + β	580	300
Second generation biomaterials (1990-till date)
Ti-13Nb-13Zr Wrought	ASTM F1713	79-84	973-1037	Metastabe β	500	335
Ti-12Mo-6Zr-2Fe (TMZF)	ASTM F1813	74-85	1060-1100	β	525	410
Ti-35Nb-7Zr-5Ta (TNZT)	-	55	596	β	265
Ti-29Nb-13Ta-4.6Zr	-	65	911	β
Ti-35Nb-5Ta-7Zr-0.40 (TNZTO)	-	66	1010	β	450
Ti-15Mo-5Zr-3Al	-	82		β
Ti-Mo	ASTM F2066			β

Fig. 7. Ti6Al4V bone plates. (a) The ulna bone plate; (b) The radial bone plate; (c) The clavicular bone plate; (d) The ulna olecranon bone plate; (e) The ankle bone plate; (f) The calcaneal bone plate.

Table 5 Mechanical properties of different synthetic polymers studied as bone plate biomaterials [79,102].

Materials	Elastic modulus (GPa)	Tensile strength (MPa)
HDPE	0.88	35
PTFE	0.50	28
PA	2.10	67
PMMA	2.55	59
PET	2.85	61
PEEK	8.30	139
PS	2.65	75
PLA	2.40	60

Fig. 8. Comparison between N,N-dodecyl,methyl-PEI-coated (a, b) and uncoated (c, d) stainless steel plate chips obtained in parallel during the surgical implantation to independently validate the bactericidal activity applied to hardware in the operating theater. Wells containing coated plate chips remained clear (a) and devoid of biofilm when analyzed under SEM (b). In contrast, uncoated plate chips presented with turbid wells consistent with bacterial growth (c) and massive biofilm formation (d; biofilm (*), coalescing S. aureus cocci (arrow)). Reprinted from Ref. [111] with permission.

Fig. 9. A spatiotemporal cascade of multiple endogenous factors controls normal bone regeneration during fracture repair in four stages. PDGF: platelet derived growth factor; VEGF: vascular endothelial growth factor; FGF: fibroblast growth factor; TNF: tumor necrosis factor; SDF: stormal cell-derived factor; IGF: insulin-like growth factor; BMP: bone morphogenetic protein; OPG: osteoprotegerin; IL: interleukin; TGF: transforming growth factor; Ang: angiopoietin; M-CSF: macrophage colony stimulating factor; RANK: receptor activator of nuclear factor κB; RANKL: RANK-ligand. Reprinted from Ref. [123] with permission.

Table 6 Effects of biological factors, drugs and metallic ions for fracture healing [6,79,[124], [125], [126], [127], [128], [129]].

Category	Designation	Efficacy	Outcomes
Inflammatory Growth Factors	TNF-α	Promote bone resorption by enhancing osteoclast differentiation and activity.
Inflammatory Growth Factors	ILs	IL-1: stimulate IL-6 secretion in osteoblasts and promote the formation of primary callus and angiogenesis at the injured site. IL-6: essential for the early phases of fracture healing and can promote monocytes differentiation to osteoclasts and also influence MSCs to the pre-osteoblast fate; recruit monocytes/macrophages. IL-11 and IL-17: promote bone resorption by enhancing osteoclast differentiation and activity. IL-10 and IL-13: inhibite bone resorption by enhancing osteoclast differentiation and activity.	IL-6: Significantly increased BMP-2/ACSb) -induced bone mass via IL-6 injection. IL-3: Enhanced bone formation.
Angiogenic Growth Factors	VEGF	Regulates the recruitment, survival and activity of endothelial cells, osteoblasts and osteoclasts; mediated capillary invasion	Increase percent calcified callus and increased vascu- larity in soft tissue surrounding fracture;
	PDGFs	Targets MSCs to promote proliferation and angiogenesis, connector between the cellular components and contributors of the osteoblast differentiation process,	Increased callus formation, increased rate of union.
	FGFs	Regulate cell migration, proliferation, and differentiation. stimulates capillary growth by modulating endothelial cell fate as well as MSCs.	Faster callus formation of fracture and higher percentages of fracture union.
Osteogenic Growth Factors	BMPs	Stem cell commitment of chondrogenic and osteogenic lineages, chondrocyte hypertophy and coupled remodelling, participate in the regulation of osteoblast lineage-specific differentiation and later bone formation, osteogenic activity in bone formation in ectopic and orthotopic sites	Increased callus size, increase stiffness
Systemic Factors	PTH	Chondrocyte and osteoblast proliferation, delayed chondrocyte hypertophy, increased coupled remodelling	Increased callus size, bone mass and mineral content, increase stiffness and strength.
Systemic Factors	Calcitonin	Reduce blood calcium and promotes bone formation via inhibiting bone removal by osteoclasts and enhance bone generation by osteoblasts.
Drugs	Alendronate	Inhibit osteoclast-mediated bone resorption and also expedite the bone-remodeling activity of osteoblasts	Increased callus formation, bone mass.
Trace elements	Mg	Stimulate the dorsal root ganglion (DRG), leading to the rise of calcitonin gene related peptide (CGRP) expression. Next, the rise of CREG expression enhanced the osteogenesis differentiation of the MSCs, which promote the formation of callus around the Mg implant.	Increased callus size, bone mass and mineral content, increase stiffness and strength.

Table 6 Effects of biological factors, drugs and metallic ions for fracture healing [6,79,[124], [125], [126], [127], [128], [129]].

Category	Designation	Efficacy	Outcomes
Inflammatory Growth Factors	TNF-α	Promote bone resorption by enhancing osteoclast differentiation and activity.
Inflammatory Growth Factors	ILs	IL-1: stimulate IL-6 secretion in osteoblasts and promote the formation of primary callus and angiogenesis at the injured site. IL-6: essential for the early phases of fracture healing and can promote monocytes differentiation to osteoclasts and also influence MSCs to the pre-osteoblast fate; recruit monocytes/macrophages. IL-11 and IL-17: promote bone resorption by enhancing osteoclast differentiation and activity. IL-10 and IL-13: inhibite bone resorption by enhancing osteoclast differentiation and activity.	IL-6: Significantly increased BMP-2/ACSb) -induced bone mass via IL-6 injection. IL-3: Enhanced bone formation.
Angiogenic Growth Factors	VEGF	Regulates the recruitment, survival and activity of endothelial cells, osteoblasts and osteoclasts; mediated capillary invasion	Increase percent calcified callus and increased vascu- larity in soft tissue surrounding fracture;
	PDGFs	Targets MSCs to promote proliferation and angiogenesis, connector between the cellular components and contributors of the osteoblast differentiation process,	Increased callus formation, increased rate of union.
	FGFs	Regulate cell migration, proliferation, and differentiation. stimulates capillary growth by modulating endothelial cell fate as well as MSCs.	Faster callus formation of fracture and higher percentages of fracture union.
Osteogenic Growth Factors	BMPs	Stem cell commitment of chondrogenic and osteogenic lineages, chondrocyte hypertophy and coupled remodelling, participate in the regulation of osteoblast lineage-specific differentiation and later bone formation, osteogenic activity in bone formation in ectopic and orthotopic sites	Increased callus size, increase stiffness
Systemic Factors	PTH	Chondrocyte and osteoblast proliferation, delayed chondrocyte hypertophy, increased coupled remodelling	Increased callus size, bone mass and mineral content, increase stiffness and strength.
Systemic Factors	Calcitonin	Reduce blood calcium and promotes bone formation via inhibiting bone removal by osteoclasts and enhance bone generation by osteoblasts.
Drugs	Alendronate	Inhibit osteoclast-mediated bone resorption and also expedite the bone-remodeling activity of osteoblasts	Increased callus formation, bone mass.
Trace elements	Mg	Stimulate the dorsal root ganglion (DRG), leading to the rise of calcitonin gene related peptide (CGRP) expression. Next, the rise of CREG expression enhanced the osteogenesis differentiation of the MSCs, which promote the formation of callus around the Mg implant.	Increased callus size, bone mass and mineral content, increase stiffness and strength.

Fig. 10. Optical images of the plate samples (a) without and (b) with the coating. The arrows indicate the locations of the coatings. The scale bars represent 3 mm. Scanning electron micrographs of the surfaces (A) without and (B, C) with the coating on the AL-Az-CH_P. The scale bars represent (A, B) 100 μm; (e) In vitro drug release profiles of the AL-Az-CH_P with and without lysozyme. Reprinted from Ref. [129] with permission.

Fig. 11. Pure Mg plates and screws used for the bone fracture fixation. (a-c) Osteosynthesis of a cranio-osteoplasty with a biodegradable pure magnesium plate system in miniature pigs; (d-e) Fixation of a rabbit ulna fracture with pure Mg fixation plates and screws. Reprinted from Ref. [56,132] with permission.

Fig. 12. Summary of (a) ultimate tensile strength, (b) elongation and for binary Mg-X alloys in the as-cast state as a function of alloying element content. Reprinted from Ref. [133] with permission.

Fig. 13. (a) Mechanical properties and (b) degradation rate of cast and wrought magnesium alloys in Hank’s solution at 37 °C. Reprinted from Ref. [136] with permission.

Fig. 14. Degradation rates determined from various magnesium alloy in MEM solution. Reprinted from Ref. [138] with permission.

Fig. 15. Bone fracture fixation by Mg-Nd-Zn-Zr bone plate with CaP coating (a-g) and AZ31 bone plate with MAO coating (h-k). (a) Uncoated, CaP coated Mg-Nd-Zn-Zr and Ti bone plates; (b) operation on the tibia of a rabbit; (c) SEM images of CaP coating; (d) SEM images of cross-section of Ca-P coating; Radiographs of implants in tibias of New Zealand rabbits for 4 weeks after surgery: (e) uncoated Mg-Nd-Zn-Zr, (f) CaP coated Mg-Nd-Zn-Zr and (g) Ti. (h) A bone fracture defect model of 3 mm width magnesium plate implantation in the radius of New Zealand white rabbits. (i) SEM morphologies of MAO coated magnesium plates; (j) SEM morphologies of cross-section of MAO coating; (k) X-Ray Observation of the rabbits after 8 weeks postoperatively. Reprinted from Ref. [139,141] with permission.

Fig. 16. Healing process of bone fracture fixed by porous bone plate. (a) The bone fracture; (b) A thin layer of cortical bone adjacent to the bone fracture site is removed; (c) The bone fracture is fixed by a porous bone plate; (d) Accelerate bone fracture is achieved and the bone plate and bone tissue grow together to form a whole.

Fig. 17. Porous bone plate. (a) A macroscopic image of a titanium fiber plate; (b) SEM image of a titanium fiber plate; (c) Trabecular porous Ta bone plate fabricated by chemical vapor deposition; (d) Porous Ta bone plate fabricated by combination of additive manufacturing and chemical vapor deposition. Reprinted from Ref. [146] with permission.

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