A Narrative Review of Cell-Based Approaches for Cranial Bone Regeneration

Current cranial repair techniques combine the use of autologous bone grafts and biomaterials. In addition to their association with harvesting morbidity, autografts are often limited by insufficient quantity of bone stock. Biomaterials lead to better outcomes, but their effectiveness is often compromised by the unpredictable lack of integration and structural failure. Bone tissue engineering offers the promising alternative of generating constructs composed of instructive biomaterials including cells or cell-secreted products, which could enhance the outcome of reconstructive treatments. This review focuses on cell-based approaches with potential to regenerate calvarial bone defects, including human studies and preclinical research. Further, we discuss strategies to deliver extracellular matrix, conditioned media and extracellular vesicles derived from cell cultures. Recent advances in 3D printing and bioprinting techniques that appear to be promising for cranial reconstruction are also discussed. Finally, we review cell-based gene therapy approaches, covering both unregulated and regulated gene switches that can create spatiotemporal patterns of transgenic therapeutic molecules. In summary, this review provides an overview of the current developments in cell-based strategies with potential to enhance the surgical armamentarium for regenerating cranial vault defects.

Remnants-preserving ACL reconstruction using direct tendinous graft fixation: a new rat model

Background Anterior cruciate ligament (ACL) repair techniques are new emerging strategies prevailing, in selected cases, over standard reconstruction of the ACL with excision of its remnants. Mid-substance ACL tears represent a challenge for ACL repair techniques, and remnants-preserving ACL reconstruction (rp-ACLR) using an autograft remains the recommended treatment in this situation. However, morbidity associated with the autograft harvesting prompts the need for alternative surgical strategies based on the use of synthetic scaffolds. Relevant small animal models of mid-substance tears with ACL remnants preservation and reconstruction are necessary to establish the preliminary proof of concept of these new strategies. Methods A rat model of rp-ACLR using a tendinous autograft after complete mid-substance ACL transection was established. Twelve weeks following surgery, clinical outcomes and knee joints were assessed through visual gait analysis, Lachman tests, thigh perimeter measurements, magnetic resonance imaging, micro-computed tomography, and histology, to evaluate the morbidity of the procedure, accuracy of bone tunnel positioning, ACL remnants fate, osteoarthritis, and autograft bony integration. Results were compared with those obtained with isolated ACL transection without reconstruction and to right non-operated knees. Results and discussion Most operated animals were weight-bearing the day following surgery, and no adverse inflammatory reaction has been observed for the whole duration of the study. Autograft fixation with cortical screws provided effective graft anchorage until sacrifice. Healing of the transected ACL was not observed in the animals in which no graft reconstruction was performed. rp-ACLR was associated with a reduced degeneration of the ACL remnants (p = 0.004) and cartilages (p = 0.0437). Joint effusion and synovitis were significantly lower in the reconstructed group compared to the transected ACL group (p = 0.004). Most of the bone tunnel apertures were anatomically positioned in the coronal and/or sagittal plane. The most deviated bone tunnel apertures were the tibial ones, located in median less than 1 mm posteriorly to anatomical ACL footprint center. Conclusion This study presents a cost-effective, new relevant and objective rat model associated with low morbidity for the preliminary study of bio-implantable materials designed for remnants-preserving ACL surgery after mid-substance ACL tear.

Numerical biomechanics modelling of indirect mitral annuloplasty treatments for functional mitral regurgitation

Mitral valve regurgitation (MR) is a common valvular heart disease where an improper closure leads to leakage from the left ventricle into the left atrium. There is a need for less-invasive treatments such as percutaneous repairs for a large inoperable patient population. The aim of this study is to compare several indirect mitral annuloplasty (IMA) percutaneous repair techniques by finite-element analyses. Two types of generic IMA devices were considered, based on coronary sinus vein shortening (IMA-CS) to reduce the annulus perimeter and based on shortening of the anterior–posterior diameter (IMA-AP). The disease, its treatments, and the heart function post-repair were modelled by modifying the living heart human model (Dassault Systèmes). A functional MR pathology that represents ischaemic MR was generated and the IMA treatments were simulated in it, followed by heart function simulations with the devices and leakage quantification from blood flow simulations. All treatments were able to reduce leakage, the IMA-AP device achieved better sealing, and there was a correlation between the IMA-CS device length and the reduction in leakage. The results of this study can help in bringing IMA-AP to market, expanding the use of IMA devices, and optimizing future designs of such devices.

A Review of Tissue Engineering for Periodontal Tissue Regeneration

Periodontal disease is one of the most common diagnoses in small animal veterinary medicine. This infectious disease of the periodontium is characterized by the inflammation and destruction of the supporting structures of teeth, including periodontal ligament, cementum, and alveolar bone. Traditional periodontal repair techniques make use of open flap debridement, application of graft materials, and membranes to prevent epithelial downgrowth and formation of a long junctional epithelium, which inhibits regeneration and true healing. These techniques have variable efficacy and are made more challenging in veterinary patients due to the cost of treatment for clients, need for anesthesia for surgery and reevaluation, and difficulty in performing necessary diligent home care to maintain oral health. Tissue engineering focuses on methods to regenerate the periodontal apparatus and not simply to repair the tissue, with the possibility of restoring normal physiological functions and health to a previously diseased site. This paper examines tissue engineering applications in periodontal disease by discussing experimental studies that focus on dogs and other animal species where it could potentially be applied in veterinary medicine. The main areas of focus of tissue engineering are discussed, including scaffolds, signaling molecules, stem cells, and gene therapy. To date, although outcomes can still be unpredictable, tissue engineering has been proven to successfully regenerate lost periodontal tissues and this new possibility for treating veterinary patients is discussed.

The Addition of a Krackow Rip Stop Suture Augment After Achilles Tendon Debridement for Insertional Achilles Tendinopathy: A Biomechanical Study

Background In the operative treatment of insertional Achilles tendinopathy, the Achilles tendon is often released from its insertion to allow for adequate debridement of pathologic tissue. The use of a double row suture anchor construct has become increasingly favorable among surgeons after Achilles tendon debridement. This study hypothesized that the addition of a Krackow rip stop suture augment to the double row suture anchor construct would increase the repair’s maximum load to failure. A biomechanically stronger repair would potentially decrease the risk of catastrophic failure with early weight-bearing or accidental forced dorsiflexion after operative management for insertional Achilles tendinopathy. Methods Fourteen cadaveric specimens were used to compare the 2 repair techniques. Achilles tendons were debrided and repaired using either a double row suture anchor with and without the additional Krackow rip stop suture augment. The 2 repair techniques were compared using an axial-torsion testing system to measure average load to failure. Results The average load to failure for the double row suture anchor repair alone was 152.00 N. The average load to failure for the tendons with the double row suture anchor with the Krackow rip stop augment was 383.08 N. An independent-samples Mann-Whitney U-test was conducted and the suture anchor plus Krackow augment group had a significantly higher load to failure ( P = .011, Mann-Whitney U = 5.00, n1 = n2 = 7, P < .05, 2-tailed). Conclusion This study confirmed that the addition of a Krakow rip stop augment to the double row suture anchor is able to increase the maximum load to failure when compared to the double row suture anchor alone. These results suggest the potential of this added technique to decrease the risk of catastrophic failure.

Chondrocytes isolation from hyaline cartilage by continuous monitoring method

Background: Articular cartilage has poor regenerative capacities. Numerous cartilage repair techniques are known, including implantation of autologous chondrocytes. Material and methods: From 18 rabbits pieces of cartilage were harvested from femoral condyle. Minced cartilage was treated with 0.25% trypsin-EDTA. In the 1st group (n=9) the cartilage was digested with 0.6% collagenase in 15 ml tubes by shaking in incubator at 37°C, 5%CO2 . In the 2nd group (n=9) digestion was performed in 25cm2 cell culture flasks placed on the lateral side, monitoring the process under a microscope after 120 minutes. The isolated cells were cultured to a 80-90% confluence. The chondrocytes were identified using histochemical staining after culturing for 16 days in overconfluence. Results: Chondrocytes isolation in the 1st group lasted a fixed 360 minutes, in the 2nd group – 140±10 minutes. In the 1stgroup were isolated 9.2x104 ±3.1x104 chondrocytes with a viability of 85.36±16.41%, but in the 2nd group – 1.6x105 ±3.4x104 chondrocytes with a viability of 98.09±3.85%. The mean period of cell culture in the 1st group was 15±2 days, in the 2nd group – 11±3 days. In first passage of the 1st group were obtained – 1.2x106 ±4.3x105 chondrocytes and in the 2nd group – 2.92x106 ±3.6x105 chondrocytes. The secreted extracellular matrix by chondrocytes was stained specifically for cartilaginous tissue. Conclusions: The method used for chondrocytes isolation has a direct impact on the number of isolated cells, their viability, but also upon the culture period and the number of cells obtained during the first passage.

Case Study of Strength Calculation and the Possible Repair Options for Screw Thread Damages

Thread Strength and repair capability are critical to successful screw joints for any mechanical assembly. This paper explores the effect of the thread damage utilizing hand calculations, the margin of safety (MOS) for internal & external threads and compares with the required design criteria limit. Hence, the reduction in thread capability is analyzed in terms of shear and bearing strength of threads. This paper also emphasizes the Industry-standard repair techniques such as Helical inserts, Oversize inserts, and Twinserts with limitations and expected process/techniques. Advanced thread repairs in the market such as solid-body thread inserts (key-style, Time-sert, Big-sert) are also discussed Keywords: Thread damages, Shear strength, bearing strength. STI (Screw thread insert)