Engineering immunomodulatory and osteoinductive implant surfaces via mussel adhesion-mediated ion coordination and molecular clicking

Immune response and new tissue formation are important aspects of tissue repair. However, only a single aspect is generally considered in previous biomedical interventions, and the synergistic effect is unclear. Here, a dual-effect coating with immobilized immunomodulatory metal ions (e.g., Zn2+) and osteoinductive growth factors (e.g., BMP-2 peptide) is designed via mussel adhesion-mediated ion coordination and molecular clicking strategy. Compared to the bare TiO2 group, Zn2+ can increase M2 macrophage recruitment by up to 92.5% in vivo and upregulate the expression of M2 cytokine IL-10 by 84.5%; while the dual-effect of Zn2+ and BMP-2 peptide can increase M2 macrophages recruitment by up to 124.7% in vivo and upregulate the expression of M2 cytokine IL-10 by 171%. These benefits eventually significantly enhance bone-implant mechanical fixation (203.3 N) and new bone ingrowth (82.1%) compared to the bare TiO2 (98.6 N and 45.1%, respectively). Taken together, the dual-effect coating can be utilized to synergistically modulate the osteoimmune microenvironment at the bone-implant interface, enhancing bone regeneration for successful implantation.

Analysis of Mechanical Properties and Permeability of Trabecular-Like Porous Scaffold by Additive Manufacturing

Human bone cells live in a complex environment, and the biomimetic design of porous structures attached to implants is in high demand. Porous structures based on Voronoi tessellation with biomimetic potential are gradually used in bone repair scaffolds. In this study, the mechanical properties and permeability of trabecular-like porous scaffolds with different porosity levels and average apertures were analyzed. The mechanical properties of bone-implant scaffolds were evaluated using finite element analysis and a mechanical compression experiment, and the permeability was studied by computational fluid dynamics. Finally, the attachment of cells was observed by confocal fluorescence microscope. The results show that the performance of porous structures can be controlled by the initial design of the microstructure and tissue morphology. A good structural design can accurately match the performance of the natural bone. The study of mechanical properties and permeability of the porous structure can help address several problems, including stress shielding and bone ingrowth in existing biomimetic bone structures, and will also promotes cell adhesion, migration, and eventual new bone attachment.

Femoral Stems With Porous Lattice Structures: A Review

Cementless femoral stems are prone to stress shielding of the femoral bone, which is caused by a mismatch in stiffness between the femoral stem and femur. This can cause bone resorption and resultant loosening of the implant. It is possible to reduce the stress shielding by using a femoral stem with porous structures and lower stiffness. A porous structure also provides a secondary function of allowing bone ingrowth, thus improving the long-term stability of the prosthesis. Furthermore, due to the advent of additive manufacturing (AM) technology, it is possible to fabricate femoral stems with internal porous lattices. Several review articles have discussed porous structures, mainly focusing on the geometric design, mechanical properties and influence on bone ingrowth. However, the safety and effectiveness of porous femoral stems depend not only on the characteristic of porous structure but also on the macro design of the femoral stem; for example, the distribution of the porous structure, the stem geometric shape, the material, and the manufacturing process. This review focuses on porous femoral stems, including the porous structure, macro geometric design of the stem, performance evaluation, research methods used for designing and evaluating the femoral stems, materials and manufacturing techniques. In addition, this review will evaluate whether porous femoral stems can reduce stress shielding and increase bone ingrowth, in addition to analyzing their shortcomings and related risks and providing ideas for potential design improvements.

Use of a New Off-the-shelf 3D-printed Trabecular Titanium Acetabular Cup in Chinese Patients Undergoing Hip Revision Surgery: Short- to Mid-term Clinical and Radiological Outcomes

Background: Revision total hip arthroplasty (THA) has been a challenge for surgeons. The purpose of this study was to explore the short-to mid-term clinical and radiological outcomes of Chinese patients who underwent revision THA using a new off-the-shelf three-dimensional (3D)-printed trabecular titanium (TT) acetabular cup by comparison with a conventional porous coated titanium acetabular cup, to provide a reference for the recommendation of this prostheses.Methods: A retrospective analysis of 57 patients (57 hips) who received revision THA was performed from January 2016 to June 2019. A total of 23 patients received 3D-printed cups (observation group) and 34 patients received non-3D-printed cups (control group). Clinical scores including Visual Analogue Scale (VAS), Harris Hip Score (HHS) and Short Form 36 (SF-36), upward movement of the hip center of rotation（HCOR）and limb-length discrepancy (LLD), stabilization and bone ingrowth of cups were compared between two groups. The multivariate linear regression was used to determine the factors potentially influencing the HHS score. Postoperative complications in the two groups were also recorded. Results: All 57 patients were routinely followed up. The average follow-up durations in the control and observation groups were 43.57 ± 13.68 (24–65) months and 41.82 ± 11.44 (24–64) months, respectively (p = 0.618). The postoperative clinical scores significantly improved in both groups compared to the preoperative scores (p < 0.05). The VAS score did not significantly differ between the groups at 3 or 12 months postoperatively, or at the last follow-up (p > 0.05). The HHS and SF-36 scores did not significantly differ between the groups at 3 months postoperatively (p > 0.05) but differed at 12 months postoperatively and the last follow-up (p < 0.05). Compared with the control group, the postoperative recovery of HCOR and LLD was better in the observation group (p < 0.05). All cups remained stable, with no loosening throughout the follow-up period. But the observation group had a significantly better rate of bone ingrowth compared to the control group (p = 0.037). Multivariate linear regression analysis showed that different cup types, upward movement of the HCOR, and LLD influenced the HHS score at the last follow-up (p < 0.05). None of the patients exhibited severe postoperative complications.Conclusion: The new off-the-shelf 3D-printed TT acetabular cup demonstrated encouraging short-to mid-term clinical outcomes in Chinese patients. It can effectively relieve pain, improve hip function, provide satisfactory biological fixation and high survival rate. But further follow up is necessary to assess its long-term outcomes.

Finite Element Analysis of Porous Ti-6Al-4V Alloy Structures for Biomedical Applications

In this article, design and finite element simulation of porous Ti-6Al-4V alloy structures was presented. Typically, titanium and titanium alloy implants can be manufactured with required pore size and porosity volume by using powder bed fusion techniques due to advancement in additive manufacturing technologies. However, the mismatch of elastic modulus between human cortical bone and the dense Ti-6Al-4V alloy implant resulted in stress shielding which accelerate the implant failure. The porous implant structures help in reduce the mismatch of elastic modulus between the cortical bone and implant structure and also improve the bone ingrowth. Hence, the present work focuses on design of Ti-6Al-4V alloy porous structures with various porosities ranging from 10% to 70% and simulated to determine the elastic modulus suitable for human cortical bone. The sample with 45% porosity is found to be best suited for replacement of cortical bone with elastic modulus of 74Gpa, preventing stress shielding effect and enhanced chances of bone ingrowth.

Investigation of Mechanical and Biological Properties of FDM 3D-Printed PLA Scaffolds With Radial Gradient Porosity for Tissue Engineering

Scaffolds with gradient porosity have become very promising candidates for tissue engineering and bone implants because of the combination of better mechanical and biological requirements. In this paper, a novel approach is proposed to design bone scaffolds with gradient porosity similar to the structure of cortical and spongy (cancellous) bones. The radial gradient PLA scaffolds were designed to consist of three different regions with the gyroid infill and, fabricated by Fused deposition modeling (FDM). The biological and mechanical properties of the scaffolds were investigated in vitro. Dense scaffold (G100) had improved mechanical properties but showed decreased bone ingrowth properties. In addition, porous scaffolds provided enhanced biological properties but decreased in mechanical strength (G40-G20). The scaffolds with radial gradient porosity (G100-40-20) gave highest cell proliferation. Because, mean pore size is an important aspect of scaffolds for mimicking bone.

3D Printing of Macro Porous Sol-Gel Derived Bioactive Glass Scaffolds and Assessment of Biological Response

3D printing emerged as a potential game-changer in the field of biomedical engineering. Robocasting in particular has shown excellent capability to produce custom-sized porous scaffolds from pastes with suitable viscoelastic properties. The materials and respective processing methods developed so far still need further improvements in order to obtain completely satisfactory scaffolds capable of providing both the biological and mechanical properties required for successful and comprehensive bone tissue regeneration. This work reports on the sol-gel synthesis of an alkali-free bioactive glass and on its characterization and processing ability towards the fabrication of porous scaffolds by robocasting. A two-fold increase in milling efficiency was achieved by suitably adjusting the milling procedures. The heat treatment temperature exerted a profound effect on the surface area of mesoporous powders. Robocasting inks containing 35 vol.% solids were prepared, and their flow properties were characterized by rheological tests. A script capable of preparing customizable CAD scaffold geometries was developed. The printing process was adjusted to increase the technique’s resolution. The mechanical properties of the scaffolds were assessed through compressive strength tests. The biomineralization ability and the biological performance were assessed by immersing the samples in simulated body fluid (SBF) and through MTT assays, respectively. The overall results demonstrated that scaffolds with macro porous features suitable for bone ingrowth (pore sizes of ~340 mm after sintering, and a porosity fraction of ~70%) in non-load-bearing applications could be successfully fabricated by 3D printing from the bioactive glass inks. Moreover, the scaffolds exhibited good biomineralization activity and good biocompatibility with human keratinocytes, suggesting they are safe and thus suited for the intended biomedical applications.

Use of a New off-the-Shelf 3D-Printed Trabecular Titanium Acetabular Cup in Chinese Patients Undergoing Hip Revision Surgery: Short- to Mid-Term Clinical and Radiological Outcomes

Background: Revision total hip arthroplasty (THA) has been a challenge for surgeons. The purpose of this study was to explore the short-to mid-term clinical and radiological outcomes of Chinese patients who underwent revision THA using a new off-the-shelf three-dimensional (3D)-printed trabecular titanium (TT) acetabular cup by comparison with a conventional porous coated titanium acetabular cup, to provide a reference for the recommendation of this prostheses.Methods: A retrospective analysis of 57 patients (57 hips) who received revision THA was performed from January 2016 to June 2019. A total of 23 patients received 3D-printed cups (observation group) and 34 patients received non-3D-printed cups (control group). Clinical scores including Visual Analogue Scale (VAS), Harris Hip Score (HHS) and Short Form 36 (SF-36), upward movement of the hip center of rotation（HCOR）and limb-length discrepancy (LLD), stabilization and bone ingrowth of cups were compared between two groups. The multivariate linear regression was used to determine the factors potentially influencing the HHS score. Postoperative complications in the two groups were also recorded. Results: All 57 patients were routinely followed up. The average follow-up durations in the control and observation groups were 43.57 ± 13.68 (24–65) months and 41.82 ± 11.44 (24–64) months, respectively (p = 0.618). The postoperative clinical scores significantly improved in both groups compared to the preoperative scores (p < 0.05). The VAS score did not significantly differ between the groups at 3 or 12 months postoperatively, or at the last follow-up (p > 0.05). The HHS and SF-36 scores did not significantly differ between the groups at 3 months postoperatively (p > 0.05) but differed at 12 months postoperatively and the last follow-up (p < 0.05). Compared with the control group, the postoperative recovery of HCOR and LLD was better in the observation group (p < 0.05). All cups remained stable, with no loosening throughout the follow-up period. But the observation group had a significantly better rate of bone ingrowth compared to the control group (p = 0.037). Multivariate linear regression analysis showed that different cup types, upward movement of the HCOR, and LLD influenced the HHS score at the last follow-up (p < 0.05). None of the patients exhibited severe postoperative complications.Conclusion: The new off-the-shelf 3D-printed TT acetabular cup demonstrated encouraging short-to mid-term clinical outcomes in Chinese patients. It can effectively relieve pain, improve hip function, provide satisfactory biological fixation and high survival rate. But further follow up is necessary to assess its long-term outcomes.