The delivery of bone morphogenetic proteins (BMPs) to the fractured sites using carrier materials such as natural or synthetic polymers, inorganic materials, or composite materials favors tissue regeneration and remodeling resulting in improved healing response
[68][36]. The availability of BMP in the scaffold allows migration, proliferation, and differentiation of regenerative cells in the vicinity of the injury. One study evaluated the efficacy of bone healing in a nonhuman primate fibular osteotomy model using human BMP-2 in various carrier matrixes
[64][32]. The investigation found that BMP injected in calcium phosphate paste accelerated bone healing by approximately 40% compared to the healing of untreated osteotomy sites. With this combination, the mean torsion stiffness and maximum torque were equal to that of the intact fibula at 10 weeks versus torsion stiffness and maximum torque values of approximately 55% and 58%, respectively, for untreated osteotomy sites. Histological examination at this time point displayed bridging of the osteotomy sites with the bone for all carrier matrices. These results affirm that the incorporation and delivery of various biological factors to the compromised site significantly alters the healing and regeneration response and improves the outcome of percutaneous interventional strategies.
4. Mechanical Characterization of Bone/Bone Implant Devices
4.1. Flexural Test
The bone in vivo is subjected to multiple forces from daily muscular activity, impact, and gravity that causes bending, torsion, extension, and compression. Because of the natural curvature of the long bone, bone bending is the most common phenomenon induced in vivo when the bone is subjected to these internal loads. To evaluate the bending properties of the bone, one can either choose a 3-point or a 4-point test. With a 3-point test configuration, a shorter gauge specimen can be conveniently examined, whereas, a 4-point test requires a relatively longer gauge specimen. In contrast, the 4-point test has the advantage of simulating a pure bending phenomenon with minimal shear effects (shear: force acting parallel to the material’s cross-section to produce a sliding failure). In the 3-point bend test, there is an inherent influence of shear, which affects the assumptions and outcomes of these tests, e.g., increased deflection/strain or early arrival to failure from low intensity applied force/stress. However, these effects can be reduced if the experiment is designed judiciously.
During mechanical testing, a preconditioning stage precedes the main loading stage where low loads are cyclically applied to ensure loading fixtures are in direct contact with the bone surface. This helps to overcome geometrical irregularities common at the bone-fixture interface, which may otherwise lead to specimen instability on the fixture when loads are applied. Whole bone testing using a bend test can provide accurate measurements of its extrinsic properties but the measurement of intrinsic material properties may not be accurate due to geometric irregularities of the specimen and the assumptions involved. A compression or tensional test using a small-sized (cut-out) specimen is recommended in such situations.
4.2. Potting Bone Ends to Comply with Four-Point Test and Multidirectional Testing
It can be difficult to evaluate the bone specimen of a small animal in a 4-point bend test configuration because of the short gauge length. When such specimens are subjected to a 4-point bend test, the distance between the internal loading pins tends to be very small, leading to a setup similar to that of a 3-point bend test. Hence, to overcome the limitation, the ends of the bone can be potted in cylindrical or square cups filled with a low melting point bismuth alloy (Wood’s metal/Cerrobend) or bone/dental cement. Subsequently, the loads can be applied directly over the potted surface
[80,81][37][38]. This method also helps to securely anchor irregular specimens over the 4-point fixture during testing. As a potential downside, improperly aligned potted ends can introduce inadvertent shear effects but can be managed with custom-designed alignment fixtures, as discussed in
[82,83,84][39][40][41].
The bone’s unique geometry and material anisotropy make its bending properties dependent on the testing plane. It may, therefore, be necessary to perform flexural testing in several directions to accurately quantify its mechanical properties. Bramer et al. developed an optimized mechanical testing model to characterize bone properties for use with 4-point testing
[80][37]. This test configuration was modified from the test setup described by Foux et al., where the authors used a 3-point testing scheme in 24 directions, perpendicular to the long axis of the bone, to characterize its mechanical properties
[81][38]. In the study by Bramer et al., the test specimens were fitted in cylindrical metal cups filled with low melting bismuth alloy
[80][37]. The metal cups had 24 grooves corresponding to 24 testing orientations. The specimen was kept in a custom fixture and subjected to nondestructive testing under axial loading in a 4-point bend configuration. During the test, the specimen was retrieved from the fixture, rotated 15°, and replaced in the fixture for testing in the succeeding orientation. This procedure was carried out until testing was completed in 24 directions (360°), i.e., throughout the specimen’s circumference. The mechanical properties were then characterized in terms of stiffness index, area ratio, flatness ratio, and inclination for these orientations.
4.3. Torsional Test
Since long bones in the body are continuously subjected to twisting forces, it is important to evaluate the mechanical performance of the bone or bone-implant devices under torsion
[85][42]. Torsional testing applies loading to the entire specimen’s length to simulate fractures commonly encountered in clinics. In contrast, compression or flexural test applies concentrated load that may lead to local deformation and the appearance of late fracture or specimen crushing. A torsional test is conducted to obtain useful information such as torsional shear stress or strain, maximum torque, shear modulus, etc.
4.4. Hardness/Indentation Test
The bone is a composite structure that obtains unique biomechanical properties from the spatial organization of inorganic (hydroxyapatite crystallites, ~60%) and organic (mostly, type I fibrillar collagen, ~30%) material in a heterogeneous matrix
[87][43]. The hierarchical molecular organization of constituent elements at a particular site determines the biological/mechanical properties of the bone (bone quality, fragility, load bearing capacity, etc.), and varies throughout the bone geometry. It is, therefore, important to ascertain the properties of the constituents elements at the micro/nano level in various regions to understand the structural performance of the bone. Bone hardness testing examines the ability to resist deformation when penetrated with an indenter
[88][44]. Hardness testing is classified based on the size of the indenter (Brinell, Rockwell, Vickers, Knoop) employed for testing and the hardness value typically varies according to the sectional region that is indented
[89][45]. Hardness testing provides a better understating of the strength of the bone (bone quality) in an in vivo environment and is particularly useful for bone-related research.
5. Summary
Percutaneous osteoplasty with reinforcement is emerging as a new therapeutic model for patients with induced or impending fractures from bone metastases or osteoporosis. These patients often present with compromised bone strength or weak health (strictly “non-surgical” patients) that prevents them from undergoing invasive surgical fixation procedures under general anesthesia. The supplementation is required as cement augmentation alone lacks sufficient strength for bone union and stabilization, esp. weight-bearing bones. Due to an obvious lack of qualified materials for reinforcement-osteoplasty, researchers have improvised radio-surgical use materials for proof-of-concept verification with limited success
[12,13,48][20][46][47]. Reinforcement osteoplasty involves strengthening bone toughness with durability-awarding materials that mimic “rebar” in the background of cementing material. Because of the percutaneous nature of the application, materials need to be sized accordingly so that they can fit and be delivered via a small opening or “access” made through the skin into the cortical region. The requirements of reinforcement implants can be a major design/ technical challenge as it requires them to be biocompatible, flexible (to allow insertion at an angle), and miniature as well as sturdy (after deployment at the target site) to render resilient support. Failure to fulfill these criteria may produce no appreciable results. For instance, authors reported no added benefit with osteoplasty (PMMA cement) alone or in combination with Kirschner wires (K-wires) to resist bending stress in a cadaveric human diaphyseal model possibly from the use of suboptimal composite materials
[48][47]. The volume of cement injected also plays a key role in determining the strength of fixation. Because of the enormous built-in back pressure and the quick onset of polymerization, it may not be usually feasible to manually inject cement volumes greater than 6–8 mL in the form of a single cohesive ball. In such scenarios, the use of an automated hydraulic-force cement injector
[96,97][48][49] or a robotic injection device as described by Garnon et al.
[98][50] may be preferred.
In vitro mechanical assessment provides insights into the feasibility of these novel procedures and devices that are designed to undertake loads and provide stability for a wide array of orthopedic applications. Various test methods have been developed to characterize the mechanical properties of these devices, and the intended use and location in vivo determine the types of tests that need to be executed and the parameters to look for. PMMA bone cement has superior axial compressive strength and capacity to withstand compression in flat bones like the spine and hip
[40][51]. However, it has low torsional, shear, and bending stress handling capacity
[36][18] and carries a risk of secondary fracture when applied to overcome long bone neoplastic defects. Studies report 8–9% of secondary long bone fractures in metastatic patients following osteoplasty
[30][52]. In the event of secondary fracture, further fixation is almost impractical because of the permanent closure of the internal void from cement filling. Calcium phosphate cement may be preferable over PMMA bone cement for fracture repair in the given context because of its superior biological and osteogenic properties
[99][53]. However, the inferior mechanical strength of calcium phosphate cement over PMMA cement requires further research to address this limitation.
Percutaneous osteoplasty with a range of adjunctive reinforcement is implemented on a case-by-case basis in clinics for the consolidation of long bone fractures (impending/pathological) and has produced encouraging results
[13,37][19][20]. However, these studies lack adequate preclinical biomechanical characterization and the outcomes may be limited to short-term gains. Further studies are needed to evaluate the long-term benefits of these procedures. Lack of osteointegration with the native tissues and non-osteoconductive properties of the implant are the most common causes of infections and imminent failures; therefore, research efforts need to be directed to find optimal solutions with a focus on physical, mechanical, and biochemical factors present in vivo. The challenges can be partly addressed with the development of next-generation bone cement composed of various osteogenic growth factors and possibly antitumor/anti-inflammatory drugs that can positively impact molecular and cellular processes and allow bonding and integration with the skeletal tissues in the targeted region without inflammation. The transformation of bone cement into an osteosynthetic material instead of being limited to a space filler heralds new bone growth and may alleviate concerns related to poor stress handling capability. Extraosseous cement leakage during percutaneous osteoplasty procedures is also a common concern that can potentially cause inflammation, pain, and tissue injury, and can be overcome with the use of an optimally viscous cement and following a cautious surgical approach
[100][54]. While there is a clear lack of sufficient clinical studies to support percutaneous reinforcement, the potential benefits in terms of pain relief, mechanical stability, and early facilitation of weight-bearing bones with bioengineered scaffold should not be discounted. Proper guidance on patient selection, surgical efficacy, and related complications based on the outcomes of large-scale studies and longer follow-ups are awaited. Moving forward, emphasis needs to be given to combination treatment that includes novel biomaterials with biocompatible and bioactive properties that can provide synergy in supplementing bone strength by aiding new bone formation, restoring anatomical defects and physiological function, and pain regression for percutaneous applications.