3D-printed MgO nanoparticle loaded polycaprolactone ß-tricalcium phosphate composite scaffold for bone tissue engineering applications: In-vitro and in-vivo evaluation.

Magnesium (Mg) plays an important role in controlling bone apatite structure and density and is a potential bioactive material in repairing critical-sized bone defects. In this study, we aimed to evaluate the effect of adding NanoMgO to polycaprolactone/beta-tricalcium phosphate (PCL/ß-TCP) scaffolds on bone regeneration. Novel 3D-printed porous PCL/ß-TCP composite scaffolds containing 10% nanoMgO were fabricated by fused deposition modeling (FDM) and compared with PCL/ß-TCP (1:1) scaffolds (control). The morphology and physicochemical properties of the scaffolds were characterized by ATR-FTIR, XRD, scanning electron microscope-energy dispersive X-ray analysis (SEM-EDX), transmission-electron-microscopy (TEM), water contact angle, and compressive strength tests and correlated to its cytocompatibility and osteogenic capacity in-vitro. To evaluate in-vivo osteogenic capacity, bone-marrow-derived stem cell (BMSC)-loaded scaffolds were implanted into 8 mm rat critical-sized calvarial defects for 12 weeks. The hydrophilic scaffolds showed 50% porosity (pore size = 504 µm). MgO nanoparticles (91.5 ± 27.6 nm) were homogenously dispersed and did not adversely affect BMSCs' viability and differentiation. Magnesium significantly increased elastic modulus, pH, and degradation. New bone formation (NBF) in Micro-CT was 30.16 ± 0.31% and 23.56 ± 1.76% in PCL/ß-TCP/nanoMgO scaffolds with and without BMSCs respectively, and 19.38 ± 2.15% and 15.75 ± 2.24% in PCL/ß-TCP scaffolds with and without BMSCs respectively. Angiogenesis was least remarkable in PCL/ß-TCP compared with other groups (p < .05). Our results suggest that the PCL/ß-TCP/nanoMgO scaffold is a more suitable bone substitute compared to PCL/ß-TCP in critical-sized calvarial defects.

Prefabrication technique by preserving a muscular pedicle from masseter muscle as an in vivo bioreactor for reconstruction of mandibular critical-sized bone defects in canine models.

In vivo bioreactors serve as regenerative niches that improve vascularization and regeneration of bone grafts. This study has evaluated the masseter muscle as a natural bioreactor for ßTCP or PCL/ßTCP scaffolds, in terms of bone regeneration. The effect of pedicle preservation, along with sole, or MSC- or rhBMP2-combined application of scaffolds, has also been studied. Twenty-four mongrel dogs were randomly placed in six groups, including ßTCP, ßTCP/rhBMP2, ßTCP/MSCs, PCL/ßTCP, PCL/ßTCP/rhBMP2, and PCL/ßTCP/MSCs. During the first surgery, the scaffolds were implanted into the masseter muscle for being prefabricated. After 2 months, each group was divided into two subgroups prior to mandibular bone defect reconstruction; one with a preserved vascularized pedicle and one without. After 12 weeks, animals were euthanized, and new bone formation was evaluated using histological analysis. Histological analysis showed that all ß-TCP scaffold groups had resulted in significantly greater rates of new bone formation, either with a pedicle surgical approach or non-pedicle surgical approach, comparing to their parallel groups of ßTCP/PCL scaffolds (p ≤ .05). Pedicled ß-TCP scaffold groups that were treated with either rhBMP2 (48.443% ± 0.250%) or MSCs (46.577% ± 0.601%) demonstrated the highest rates of new bone formation (p ≤ .05). Therefore, masseter muscle can be used as a local in vivo bioreactor with potential clinical advantages in reconstruction of human mandibular defects. In addition, scaffold composition, pedicle preservation, and treatment with MSCs or rhBMP2, influence new bone formation and scaffold degradation rates in the prefabrication technique.

Reconstruction of bilateral ramus-condyle unit defect using custom titanium prosthesis with preservation of both condyles.

BACKGROUND: Novel technologies for management and reconstruction of complex bony defects regarding both function and facial appearance are interestingly used in maxillofacial surgery. In the current study, we demonstrated reconstruction of a bilateral ramus-condyle unit (RCU) defect while preserving both condyles by a novel designed titanium prosthesis using virtual surgical planning (VSP), computer-aided design and manufacturing (CAD/CAM), and Selective Laser Melting (SLM) technologies. MATERIALS AND METHODS: A 3D customized titanium prosthesis was designed for a 49 -year-old patient with bilateral mandibular aggressive central giant cell granuloma (CGCG) according to mandibular normal anatomy and structure while preserving bilateral intact condyles. Finite element study was performed to investigate the effects of new design strength and the stress shielding phenomenon. The design of macro-pores inside the body of prosthesis allowed it to act as a scaffold for bone tissue engineering under load bearing conditions. RESULTS: Analysis of the strength and stress shielding phenomenon demonstrated favorable outcomes regarding the novel design. For instance, there was no stress shielding in any of the preserved condyles with regard to the size and distribution of stresses. Also, the stress distribution around the pores showed that these pores had no effect on the strength of the prosthesis. Thirty month follow-ups after reconstruction of bilateral RCU defect showed normal jaw function with a favorable facial appearance and mandibular contour. CONCLUSION: We design a novel patient-specific prosthesis with desirable biomechanical features for reconstruction of bilateral RCU defect after resection of the benign tumor with preservation of bilateral intact condyles.

Efficacy of mesenchymal stromal cells and cellular products in improvement of symptoms for COVID-19 and similar lung diseases.

At the end of 2019, respiratory coronavirus diseases 2019 (COVID-19) appeared and spread rapidly in the world. Besides several mutations, the outcome of this pandemic was the death up to 15% of hospitalized patients. Mesenchymal stromal cell therapy as a therapeutic strategy seemed successful in treatment of several diseases. Not only mesenchymal stromal cells of several tissues, but also their secreted extracellular vesicles and even secretome indicated beneficial therapeutic function. All of these three options were studied for treatment of COVID-19 as well as those respiratory diseases that have similar symptom. Fortunately, most of the outcomes were promising and optimistic. In this paper, we review in-vivo and clinical studies which have been used different sources of mesenchymal stromal cell, secreted extracellular vesicles, and secretome to improve and treat symptoms of COVID-19 and similar lung diseases.

DNA damage repair response in mesenchymal stromal cells: From cellular senescence and aging to apoptosis and differentiation ability.

Mesenchymal stromal cells (MSCs) are heterogeneous and contain several populations, including stem cells. MSCs' secretome has the ability to induce proliferation, differentiation, chemo-attraction, anti-apoptosis, and immunomodulation activities in stem cells. Moreover, these cells recognize tissue damage caused by drugs, radiation (e.g., Ultraviolet, infra-red) and oxidative stress, and respond in two ways: either MSCs differentiate into particular cell lineages to preserve tissue homeostasis, or they release a regenerative secretome to activate tissue repairing mechanisms. The maintenance of MSCs in quiescence can increase the incidence and accumulation of various forms of genomic modifications, particularly upon environmental insults. Thus, dysregulated DNA repair pathways can predispose MSCs to senescence or apoptosis, reducing their stemness and self-renewal properties. For instance, DNA damage can impair telomere replication, activating DNA damage checkpoints to maintain MSC function. In this review, we aim to summarize the role of DNA damage and associated repair responses in MSC senescence, differentiation and programmed cell death.

Effects of Different Angles of the Traction Table on Lumbar Spine Ligaments: A Finite Element Study.

BACKGROUND: The traction bed is a noninvasive device for treating lower back pain caused by herniated intervertebral discs. In this study, we investigated the impact of the traction bed on the lower back as a means of increasing the disc height and creating a gap between facet joints. METHODS: Computed tomography (CT) images were obtained from a female volunteer and a three-dimensional (3D) model was created using software package MIMICs 17.0. Afterwards, the 3D model was analyzed in an analytical software (Abaqus 6.14). The study was conducted under the following traction loads: 25%, 45%, 55%, and 85% of the whole body weight in different angles. RESULTS: Results indicated that the loading angle in the L3-4 area had 36.8%, 57.4%, 55.32%, 49.8%, and 52.15% effect on the anterior longitudinal ligament, posterior longitudinal ligament, intertransverse ligament, interspinous ligament, and supraspinous ligament, respectively. The respective values for the L4-5 area were 32.3%, 10.6%, 53.4%, 56.58%, and 57.35%. Also, the body weight had 63.2%, 42.6%, 44.68%, 50.2%, and 47.85% effect on the anterior longitudinal ligament, posterior longitudinal ligament, intertransverse ligament, interspinous ligament, and supraspinous ligament, respectively. The respective values for the L4-5 area were 67.7%, 89.4%, 46.6%, 43.42% and 42.65%. The authenticity of results was checked by comparing with the experimental data. CONCLUSIONS: The results show that traction beds are highly effective for disc movement and lower back pain relief. Also, an optimal angle for traction can be obtained in a 3D model analysis using CT or magnetic resonance imaging images. The optimal angle would be different for different patients and thus should be determined based on the decreased height of the intervertebral disc, weight and height of patients.