BACKGROUND: Exosomes, nano-sized vesicles ranging between 30 and 150 nm secreted by human cells, play a pivotal role in long-range intercellular communication and have attracted significant attention in the field of regenerative medicine. Nevertheless, their limited productivity and cost-effectiveness pose challenges for clinical applications. These issues have recently been addressed by cell-derived nanovesicles (CDNs), which are physically synthesized exosome-mimetic nanovesicles from parent cells, as a promising alternative to exosomes. CDNs exhibit structural, physical, and biological properties similar to exosomes, containing intracellular protein and genetic components encapsulated by the cell plasma membrane. These characteristics allow CDNs to be used as regenerative medicine and therapeutics on their own, or as a drug delivery system. METHODS: The paper reviews diverse methods for CDN synthesis, current analysis techniques, and presents engineering strategies to improve lesion targeting efficiency and/or therapeutic efficacy. RESULTS: CDNs, with their properties similar to those of exosomes, offer a cost-effective and highly productive alternative due to their non-living biomaterial nature, nano-size, and readiness for use, allowing them to overcome several limitations of conventional cell therapy methods. CONCLUSION Ongoing research and enhancement of CDNs engineering, along with comprehensive safety assessments and stability analysis, exhibit vast potential to advance regenerative medicine by enabling the development of efficient therapeutic interventions.

BACKGROUND: Breast cancer patients suffer from lowered quality of life (QoL) after surgery. Breast conservancy surgery (BCS) such as partial mastectomy is being practiced and studied as an alternative to solve this problem. This study confirmed breast tissue reconstruction in a pig model by fabricating a 3-dimensional (3D) printed Polycaprolactone spherical scaffold (PCL ball) to fit the tissue resected after partial mastectomy. METHODS: A 3D printed Polycaprolactone spherical scaffold with a structure that can help adipose tissue regeneration was produced using computer-aided design (CAD). A physical property test was conducted for optimization. In order to enhance biocompatibility, collagen coating was applied and a comparative study was conducted for 3 months in a partial mastectomy pig model. RESULTS: In order to identify adipose tissue and fibroglandular tissue, which mainly constitute breast tissue, the degree of adipose tissue and collagen regeneration was confirmed in a pig model after 3 months. As a result, it was confirmed that a lot of adipose tissue was regenerated in the PCL ball, whereas more collagen was regenerated in the collagen-coated Polycaprolactone spherical scaffold (PCL–COL ball). In addition, as a result of confirming the expression levels of TNF-a and IL-6, it was confirmed that PCL ball showed higher levels than PCL–COL ball. CONCLUSION Through this study, we were able to confirm the regeneration of adipose tissue through a 3-dimensional structure in a pig model. Studies were conducted on medium and large-sized animal models for the final purpose of clinical use and reconstruction of human breast tissue, and the possibility was confirmed.

Purpose: Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy. Materials and Methods: We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA. Results: Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker. Conclusion Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.

Background: Endoscopic forehead lift with cortical tunneling is an effective option for rejuvenation of the upper third of the face. Although it has been considered safe and reliable, with relatively consistent long-term results, relapse and weakening of adhesion have been common problems. Methods: We suggest the dual-tunneling method for overcoming these limitations. A total of 100 patients aged 17 to 65 years underwent forehead lifting with cortical tunneling by the senior author from August 2016 to December 2017. The single-tunnel method was applied in one half of the patients and the dual-tunnel method in the other half. Bilateral brow positions were measured immediately following surgery and 6 months later. Results: For all cases, cortical tunneling was done at the central incision and both paramedian incisions; therefore, three tunnels were used in the control group and six tunnels in the experimental group. In the single-tunnel group, relapse distances were 2.39±0.83 mm for the medial brow and 3.26±0.91 mm for the lateral brow (6 months postoperatively; n=100). The dual-tunnel group showed significantly smaller (P<0.001) relapse distances, with values of 1.69±0.46 mm and 2.17±0.59 mm for the medial and lateral brow, respectively (6 months postoperatively; n=100). The experimental group did not show an increase in complications. Conclusions The dual-tunneling method, designed to minimize the cheese-wiring effect, uses a triangular plane to avoid a focal fixation. The fixation also includes the periosteum to hold the forehead tissue in place, inducing stronger adhesion.

Postoperative temporal hollowing is a common complication of craniotomy. Damage and repositioning of the temporalis muscle can lead to a depression in the temporal side of the skull with inferior bulging, worsening aesthetic outcomes. We report a case of cranioplasty with three-dimensional (3D) printed mesh involving an additional correction using a temporalis muscle sling to help address this problem. A 3D-printed bioabsorbable mesh was prepared based on preoperative facial computed tomography, and was fixed to the hollowed area for tissue augmentation. The temporalis muscle was elevated and fanned out to its original position, and a sling was attached to a screw that was fixed to the mesh. For reinforcement, an additional sling was attached to another screw fixed to the mesh 2–3 cm vertically above the first screw. Aesthetic results were confirmed immediately after surgery and later during outpatient follow-up. Both depression and lateral bulging were resolved, and there was no delayed drooping of the temporalis muscle on 6-month follow-up. There were no complications, and the patient was satisfied with the appearance. This is a simple yet effective technique with a low risk of complications, and should be considered for postoperative temporal hollowing patients, especially those with severe lateral bulging.

Post-traumatic enophthalmos and hypoglobus are common sequelae of facial bone fractures, even after reduction surgery. They are associated with functional and esthetic issues, which may lower the quality of life. These deformities frequently present late, and adequate correction is difficult. We report three cases of late inferior orbital rim reconstructions with three-dimensional printed implants to help resolve these problems. The average duration between the traumatic event and surgery was 3 years and 4 months. One patient was treated with a completely absorbable implant and exhibited satisfactory results until the implant started to biodegrade at 1 year and 9 months after surgery. Two patients were treated with a permanent implant and demonstrated satisfactory results. However, longer follow-up periods were needed. There were no complications such as infection, diplopia, or restriction of ocular motion and the patients were satisfied with the esthetic results.

Background: Endoscopic forehead lifting is one of the most common procedures in the field of upper facial surgery. The upper third of the face determines the facial expression and plays a key role in the appearance of facial youth. After the forehead, a high hairline is one of the most important features of the upper third of the face contributing to age identification. The combined evaluation of these two features should be a basic premise of upper facial surgery. Methods: The authors present a surgical sequence in which endoscopic forehead lifting and lowering of the high hairline by means of a scalp flap advancement are carried out during the same operation. The incision line is located along the hairline. After the scalp and forehead flap are moved, they are fixed using the bone tunnel fixation method. Results: In total, 194 patients were treated with endoscopic forehead lifting and simultaneous hairline lowering between August 2018 and July 2020. On average, the patients’ hairlines were 18 mm lower and their eyebrows were 5 mm higher. No patients had serious complications. Conclusions Endoscopic forehead lifting and simultaneous hairline lowering surgery make it possible to address the entire upper third of the face in a single facial rejuvenation operation.

Background: Endoscopic forehead lifting is one of the most common procedures in the field of upper facial surgery. The upper third of the face determines the facial expression and plays a key role in the appearance of facial youth. After the forehead, a high hairline is one of the most important features of the upper third of the face contributing to age identification. The combined evaluation of these two features should be a basic premise of upper facial surgery. Methods: The authors present a surgical sequence in which endoscopic forehead lifting and lowering of the high hairline by means of a scalp flap advancement are carried out during the same operation. The incision line is located along the hairline. After the scalp and forehead flap are moved, they are fixed using the bone tunnel fixation method. Results: In total, 194 patients were treated with endoscopic forehead lifting and simultaneous hairline lowering between August 2018 and July 2020. On average, the patients’ hairlines were 18 mm lower and their eyebrows were 5 mm higher. No patients had serious complications. Conclusions Endoscopic forehead lifting and simultaneous hairline lowering surgery make it possible to address the entire upper third of the face in a single facial rejuvenation operation.

Background: Repair of the orbital floor following trauma or tumor removal remains a challenge because of its complex three-dimensional shape. The purpose of the present study is to understand normal orbital floor anatomy by investigating its differences across four groups (Caucasian American and East Asian, males and females) via facial bone computed tomography (CT). Methods: A total of 48 orbits in 24 patients between 20 and 60 years of age were evaluated. Although most patients underwent CT scanning following trauma, the orbital walls were intact in all patients. Linear and angular measurements of the orbital floor were obtained from CT images. Results: Orbital floor width, length, angle between the orbital floor and medial wall, and distance from the inferior orbital rim to the lowest point of the orbital floor did not show a statistically significant difference between groups. Angles made by the infraorbital rim, the lowest point of the floor, and the anterior border of the infraorbital fissure were statistically significantly wider in East Asian females than in male groups. The floor depth in East Asian females was significantly smaller compared to all the other groups. Conclusion East Asian female population had smaller curvature and depth of an orbital floor than the other groups, which means racial and sex-related differences should be considered in the orbital floor reconstruction.

BACKGROUND: The objectives of this study were to design polycaprolactone nanofibers with a radial pattern using a modified electrospinning method and to evaluate the effect of radial nanofiber deposition on mechanical and biological properties compared to non-patterned samples. METHODS: Radially patterned polycaprolactone nanofibers were prepared with a modified electrospinning method and compared with randomly deposited nanofibers. The surface morphology of samples was observed under scanning electron microscopy (SEM). The tensile properties of nanofibrous mats were measured using a tabletop uniaxial testing machine. Fluorescence-stained human bone marrow stem cells were placed along the perimeter of the radially patterned and randomly deposited. Their migration toward the center was observed on days 1, 4, and 7, and quantitatively measured using ImageJ software. RESULTS: Overall, there were no statistically significant differences in mechanical properties between the two types of polycaprolactone nanofibrous mats. SEM images of the obtained samples suggested that the directionality of the nanofibers was toward the central area, regardless of where the nanofibers were located throughout the entire sample. Florescence images showed stronger fluorescence inside the circle in radially aligned nanofibers, with significant differences on days 4 and 7, indicating that migration was quicker along radially aligned nanofibers than along randomly deposited nanofibers. CONCLUSIONS: In this study, we successfully used modified electrospinning to fabricate radially aligned nanofibers with similar mechanical properties to those of conventional randomly aligned nanofibers. In addition, we observed faster migration along radially aligned nanofibers than along randomly deposited nanofibers. Collectively, the radially aligned nanofibers may have the potential for tissue regeneration in combination with stem cells.
Bandages ; Bone Marrow ; Fluorescence ; Humans ; Methods ; Microscopy, Electron, Scanning ; Nanofibers ; Polymers ; Regeneration ; Stem Cells ; Wound Healing ; Wounds and Injuries