The immune response of the host towards foreign body, especially in the form of giant cell reaction against the implanted materials, is a vital factor for determining the repair outcome of bone defect. Biomaterials with good immunomodulatory capacity and suitable degradation may promote the regeneration of bone defect and osteointegration with the host. Small intestine submucosa (SIS), a decellularized material, has been shown to possess a property for inducing the M2 phenotype of macrophages. Our findings suggested that the SIS hydrogel could induce the macrophages to polarize into mixed M1/M2 phenotypes, and such phenotypes have enhanced the migration and tube formation of angiogenesis-associated cells in vitro , whilst having a mild effect on osteoclastogenesis and osteogenesis. Experiment with a rat model for critical-sized bone defect regeneration further demonstrated that the composite BMP-2@SIS hydrogel could sequentially activate M1 and M2 macrophages and promote early-stage angiogenesis, which altogether expedited final bone defect regeneration. 

Accelerated bone defect regeneration through sequential activation of the M1 and M2 phenotypes of macrophages by a composite BMP-2@SIS hydrogel: An immunomodulatory perspective

Additive manufacturing has been used to develop a variety of scaffold designs for clinical and industrial applications. Mechanical properties (i.e., compression, tension, bending, and torsion response) of these scaffolds are significantly important for load-bearing orthopaedic implants. In this study, we designed and additively manufactured porous metallic biomaterials based on two different types of triply periodic minimal surface structures (i.e., gyroid and diamond) that mimic the mechanical properties of bone, such as porosity, stiffness, and strength. Physical and mechanical properties, including compressive, tensile, bending, and torsional stiffness and strength of the developed scaffolds, were then characterised experimentally and numerically using finite element method. Sheet thickness was constant at 300 μm, and the unit cell size was varied to generate different pore sizes and porosities. Gyroid scaffolds had a pore size in the range of 600–1200 μm and a porosity in the range of 54–72%, respectively. Corresponding values for the diamond were 900–1500 μm and 56–70%. Both structure types were validated experimentally, and a wide range of mechanical properties (including stiffness and yield strength) were predicted using the finite element method. The stiffness and strength of both structures are comparable to that of cortical bone, hence reducing the risks of scaffold failure. The results demonstrate that the developed scaffolds mimic the physical and mechanical properties of cortical bone and can be suitable for bone replacement and orthopaedic implants. However, an optimal design should be chosen based on specific performance requirements.

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Mechanical Characterisation and Numerical Modelling of TPMS-Based Gyroid and Diamond Ti6Al4V Scaffolds for Bone Implants: An Integrated Approach for Translational Consideration

The periosteum plays an indispensable role in immunomodulation and osteogenesis during bone regeneration. The natural periosteum has a hierarchical structure, in which the outer fibrous layer is composed of fibrous tissue arranged in parallel, while disorganized nanofibers are found in the inner cambium layer. Herein, inspired by the nanostructure/function of the periosteum, we designed a collagen membrane aligned in an oriented manner (CMalig) to mimic the fibrous layer of the natural periosteum and thereby facilitate the M1-to-M2 phenotypic macrophage transition. The randomly oriented nanofiber membrane (CMrand) simulated the cambium layer and promoted the osteogenic differentiation of endogenous bone progenitor cells. CMalig induced the M2 polarization of RAW 264.7 cells in vitro, and numerous CD206+F4/80+ cells were observed at femur defect sites after CMalig treatment. CMrand promoted the osteogenic differentiation of periosteal stem cells and ectopic bone formation in a subcutaneous implantation model. These heterotopic ossifications were also verified in a rat Achilles tendon defect model. The biomimetic periosteum with a hierarchical structure significantly accelerated new bone formation in the rat femur defect model. These results suggest that the hierarchically structured biomimetic periosteum with immunomodulatory and osteogenic functions can be used as an alternative to periosteal autografts. 

A hierarchical biomimetic periosteum combined immunomodulatory and osteogenic functions for bone regeneration

In bone tissue engineering research, bioreactors designed for replicating the main features of the complex native environment represent powerful investigation tools. Moreover, when equipped with automation, their use allows reducing user intervention and dependence, increasing reproducibility and the overall quality of the culture process. In this study, an automated uni-/bi-directional perfusion bioreactor combinable with pulsed electromagnetic field (PEMF) stimulation for culturing 3D bone tissue models is proposed. A user-friendly control unit automates the perfusion, minimizing the user dependency. Computational fluid dynamics simulations supported the culture chamber design and allowed the estimation of the shear stress values within the construct. Electromagnetic field simulations demonstrated that, in case of combination with a PEMF stimulator, the construct can be exposed to uniform magnetic fields. Preliminary biological tests on 3D bone tissue models showed that perfusion promotes the release of the early differentiation marker alkaline phosphatase. The histological analysis confirmed that perfusion favors cells to deposit more extracellular matrix (ECM) with respect to the static culture and revealed that bi-directional perfusion better promotes ECM deposition across the construct with respect to uni-directional perfusion. Lastly, the Real-time PCR results of 3D bone tissue models cultured under bi-directional perfusion without and with PEMF stimulation revealed that the only perfusion induced a ~ 40-fold up-regulation of the expression of the osteogenic gene collagen type I with respect to the static control, while a ~ 80-fold up-regulation was measured when perfusion was combined with PEMF stimulation, indicating a positive synergic pro-osteogenic effect of combined physical stimulations. 

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An automated 3D-printed perfusion bioreactor combinable with pulsed electromagnetic field stimulators for bone tissue investigations

This paper presents pioneering results on the evaluation of noble metal film hetero-structures to improve some functional characteristics of carbon-based implant materials: carbon-composite material (CCM) and carbon-fiber-reinforced polyetheretherketone (CFR-PEEK). Metal-organic chemical vapor deposition (MOCVD) was successfully applied to the deposition of Ir, Pt, and PtIr films on these carriers. A noble metal layer as thin as 1 µm provided clear X-ray imaging of 1–2.5 mm thick CFR-PEEK samples. The coated and pristine CCM and CFR-PEEK samples were further surface-modified with Au and Ag nanoparticles (NPs) through MOCVD and physical vapor deposition (PVD) processes, respectively. The composition and microstructural features, the NPs sizes, and surface concentrations were determined. In vitro biological studies included tests for cytotoxicity and antibacterial properties. A series of samples were selected for subcutaneous implantation in rats (up to 3 months) and histological studies. The bimetallic PtIr-based heterostructures showed no cytotoxicity in vitro, but were less biocompatible due to a dense two-layered fibrous capsule. AuNP heterostructures on CFR-PEEK promoted cell proliferation in vitro and exhibited a strong inhibition of bacterial growth (p < 0.05) and high in vitro biocompatibility, especially Au/Ir structures. AgNP heterostructures showed a more pronounced antibacterial effect, while their in vivo biocompatibility was better than that of the pristine CFR-PEEK, but worse than that of AuNP heterostructures.

/pdf/biological-studies-of-new-implant-materials-based-on-carbon-2auk8qve.pdf

Biological Studies of New Implant Materials Based on Carbon and Polymer Carriers with Film Heterostructures Containing Noble Metals

Large bone defects resulting from musculoskeletal tumours, infections, or trauma are often unable to heal spontaneously. The challenge for surgeons is to avoid amputation, and provide the best functional outcomes. Allograft, vascularized fibular or iliac graft, hybrid graft, extracorporeal devitalized autograft, distraction osteogenesis, induced-membrane technique, and segmental prostheses are the most common surgical strategies to manage large bone defects. Given its optimal osteogenesis, osteoinduction, osteoconduction, and histocompatibility properties, along with the lower the risk of immunological rejection, autologous graft represents the most common used strategy for reconstruction of bone defects. However, the choice of the best surgical technique is still debated, and no consensus has been reached. The present study investigated the current reconstructive strategies for large bone defect after trauma, infections, or tumour excision, discussed advantages and disadvantages of each technique, debated available techniques and materials, and evaluated complications and new perspectives.

/pdf/strategies-for-large-bone-defect-reconstruction-after-trauma-1p5f52m3ov.pdf

Strategies for large bone defect reconstruction after trauma, infections or tumour excision: a comprehensive review of the literature.

Purpose: Osteonecrosis of the femoral head (ONFH) is common in skeletally immature patients. The management of ONFH is controversial, with limited evidence and unpredictable results. This study systematically reviewed the current operative modalities and clinical outcomes of surgical management for ONFH in skeletally immature patients. Methods: The present study was conducted according to the PRISMA 2020 guidelines. PubMed, Google Scholar, Embase, and Web of Science databases were accessed in October 2021. All the published clinical studies reporting data concerning the surgical management of ONFH in skeletally immature patients were included. Results: This review included 122 patients (127 hips). 38.2% (46 of 122) were female. The mean age of the patients was 14.2 ± 2.3 years. The mean duration of the follow-up was 55.3 ± 19.6 months. The Harris Hip Score improved from 68.8 ± 11.9 at baseline to 90.5 ± 6.5 at last follow-up (p < 0.0001). Femoral head collapse and secondary hip degeneration were the most common complications. Conclusion: Several surgical techniques are available and effective for the management of ONFH in skeletally immature patients. This study evidenced high heterogeneity of the surgical procedures and eligibility criteria. Further high-quality investigations are required to establish proper indications and surgical modalities.

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Operative Management of Avascular Necrosis of the Femoral Head in Skeletally Immature Patients: A Systematic Review

Purpose: Intense sporting activity and certain types of work increase the risk of early osteoarthritis (OA). OA can be idiopathic or associated to certain predisposing factors: female sex, obesity, history of joint injury, and joint overuse. The role of gender among the active population as a predisposing factor for OA is not well clear. This study investigated whether the risk of OA changes with age in both sexes in physically active individuals. Materials and Methods: This systematic review was conducted according to the PRISMA guidelines 2020. PubMed, Google Scholar, Embase, and Web of Science databases were accessed in April 2021. No time constrains were used for the search. All the published clinical studies reporting data about relationship between physical activity and OA were included. Results: Data from 7 articles were retrieved including 360,053 patients (271,903 males; 88,150 females). The mean age was 48.2±16.7 years. Males, under the age of 60 had a higher risk of developing OA. People undertaking intense physical activity, such as professional athletes or heavy workers, are more prone to develop early OA. Conclusion: Physically active males demonstrated a higher risk of developing OA.

Gerardo La Padula

Papers

Strategies for large bone defect reconstruction after trauma, infections or tumour excision: a comprehensive review of the literature.

Operative Management of Avascular Necrosis of the Femoral Head in Skeletally Immature Patients: A Systematic Review

The Association Between Sex and Osteoarthritis in the Physically Active Population: A Systematic Review