Suture Fiber Reinforcement of a 3D Printed Gelatin Scaffold for Its Potential Application in Soft Tissue Engineering.

Gelatin has excellent biological properties, but its poor physical properties are a major obstacle to its use as a biomaterial ink. These disadvantages not only worsen the printability of gelatin biomaterial ink, but also reduce the dimensional stability of its 3D scaffolds and limit its application in the tissue engineering field. Herein, biodegradable suture fibers were added into a gelatin biomaterial ink to improve the printability, mechanical strength, and dimensional stability of the 3D printed scaffolds. The suture fiber reinforced gelatin 3D scaffolds were fabricated using the thermo-responsive properties of gelatin under optimized 3D printing conditions (-10 °C cryogenic plate, 40-80 kPa pneumatic pressure, and 9 mm/s printing speed), and were crosslinked using EDC/NHS to maintain their 3D structures. Scanning electron microscopy images revealed that the morphologies of the 3D printed scaffolds maintained their 3D structure after crosslinking. The addition of 0.5% (w/v) of suture fibers increased the printing accuracy of the 3D printed scaffolds to 97%. The suture fibers also increased the mechanical strength of the 3D printed scaffolds by up to 6-fold, and the degradation rate could be controlled by the suture fiber content. In in vitro cell studies, DNA assay results showed that human dermal fibroblasts' proliferation rate of a 3D printed scaffold containing 0.5% suture fiber was 10% higher than that of a 3D printed scaffold without suture fibers after 14 days of culture. Interestingly, the supplement of suture fibers into gelatin biomaterial ink was able to minimize the cell-mediated contraction of the cell cultured 3D scaffolds over the cell culture period. These results show that advanced biomaterial inks can be developed by supplementing biodegradable fibers to improve the poor physical properties of natural polymer-based biomaterial inks.

Bone Fracture-Treatment Method: Fixing 3D-Printed Polycaprolactone Scaffolds with Hydrogel Type Bone-Derived Extracellular Matrix and ß-Tricalcium Phosphate as an Osteogenic Promoter.

Bone formation and growth are crucial for treating bone fractures. Improving bone-reconstruction methods using autologous bone and synthetic implants can reduce the recovery time. Here, we investigated three treatments using two different materials, a bone-derived decellularized extracellular matrix (bdECM) and ß-tricalcium phosphate (ß-TCP), individually and in combination, as osteogenic promoter between bone and 3D-printed polycaprolactone scaffold (6-mm diameter) in rat calvarial defects (8-mm critical diameter). The materials were tested with a human pre-osteoblast cell line (MG63) to determine the effects of the osteogenic promoter on bone formation in vitro. A polycaprolactone (PCL) scaffold with a porous structure was placed at the center of the in vivo rat calvarial defects. The gap between the defective bone and PCL scaffold was filled with each material. Animals were sacrificed four weeks post-implantation, and skull samples were preserved for analysis. The preserved samples were scanned by micro-computed tomography and analyzed histologically to examine the clinical benefits of the materials. The bdECM-ß-TCP mixture showed faster bone formation and a lower inflammatory response in the rats. Therefore, our results imply that a bdECM-ß-TCP mixture is an ideal osteogenic promoter for treating fractures.

Location of the Mandibular Incisive Canal Related to the Placement of Dental Implants: A Case Report.

Cone-beam computerized tomography (CBCT) can show an uncommon mandibular incisive canal that cannot be detected by panoramic radiography, which is used preoperatively to form the initial plan of the size and length of an implant fixture for surgical placement in the mandibular interforaminal area. Determination of the position and anatomical configuration of the mandibular incisive canal is challenging. The purpose of this case report is to discuss anatomical variations in the mandibular incisive canal and the mental canal by reviewing previous studies. Furthermore, we propose that the anterior loop length of the mental canal near the mental foramen, as well as the diameter of the mandibular incisive canal, should be verified by CBCT prior to performing implant surgery in the anterior mandibular area to prevent possible nerve damage.

Effect of cross-linking on the dimensional stability and biocompatibility of a tailored 3D-bioprinted gelatin scaffold.

Biocompatible and biodegradable gelatin is a good candidate bioink for use in 3D bioprinting technologies, but viscous gelatin solution has a low printability. In order to improve the poor printability of gelatin, we optimized the rheological properties of gelatin solution. 3D gelatin scaffolds were then cross-linked using physical or chemical methods to maintain the 3D structure. The physicochemical and biological differences between the two types of cross-linked gelatin scaffolds were studied. Scanning electron microscopy images revealed that the morphologies of the resulting cross-linked 3D scaffolds maintained their structural stabilities. The physically cross-linked 3D scaffolds maintained their surface sizes without a significant decrease (less than a 3% reduction in the surface size was observed) after cross-linking. To evaluate the differences in cell affinity by two types of cross-linking method, human dermal fibroblasts cultured on the cross-linked 3D scaffolds. After 14 days of culturing, DNA assays showed that the cell proliferation rate of the physically cross-linked 3D scaffold was 44% higher than that of the chemically cross-linked 3D scaffold. In conclusion, the optimized physically cross-linked 3D scaffold retained its surface size without significant decreases after cross-linking, as required by 3D-printed patient-specific tissue engineered customized scaffolds, despite the use of water-soluble gelatin hydrogels.

Three-Dimensional Culture of Salivary Gland Stem Cell in Orthotropic Decellularized Extracellular Matrix Hydrogels.

Radiotherapy in patients with cancer can kill cancer cells but also damage normal cells or tissues. During the treatment of patients with head and neck cancer or thyroid cancer, hyposalivation is a representative chronic side effect of radio-damaged salivary glands (SGs). The major symptom of hyposalivation is mouth dryness, resulting in several subsequent long-term complications. No effective therapeutic approaches have been developed to manage this symptom. In this study, we developed the first rat SG tissue-derived decellularized extracellular matrix hydrogel (DSGM-hydrogel) as a functional orthotropic bioscaffold for future efficient SG stem cell therapy. DSGM-hydrogels were characterized by rheological or biochemical analyses, and rat SG stem/progenitor cells (rSGSCs) were then subjected to three-dimensional culture in the DSGM-hydrogels. Interestingly, DSGM-hydrogel-embedded rSGSCs survived and expressed SG functional differentiation marker of amylase IA and increased enzyme activity of α-amylase in protein level, whereas they showed reduced levels of adult ductal stem/progenitor markers, including c-Kit, c-Met, and CD44. Furthermore, the expression levels of basic epithelial tight junction markers were recovered to levels similar to those naked SG tissues after culture in DSGM-hydrogels in transcription level. Therefore, our findings suggested that the DSGM-hydrogels could provide an appropriate microenvironment for stem/progenitor cell survival and a source of SG cytodifferentiation. This approach could be an applicable method to SG stem cell research as a potential source for an organoid and for clinical regenerative reagents to manage radio-damaged SGs in vivo. Impact Statement In this study, we established the first rat salivary gland (SG) tissue-derived decellularized extracellular matrix hydrogel (DSGM-hydrogel) and assessed the role of this hydrogel as a functional orthotropic bioscaffold. Our findings provide important insights into the applications of the DSGM-hydrogel as a biocompatible matrix for regenerative therapy of radio-damaged SGs.

3D Bioprinting Technologies for Tissue Engineering Applications.

Three-dimensional (3D) printing (rapid prototyping or additive manufacturing) technologies have received significant attention in various fields over the past several decades. Tissue engineering applications of 3D bioprinting, in particular, have attracted the attention of many researchers. 3D scaffolds produced by the 3D bioprinting of biomaterials (bio-inks) enable the regeneration and restoration of various tissues and organs. These 3D bioprinting techniques are useful for fabricating scaffolds for biomedical and regenerative medicine and tissue engineering applications, permitting rapid manufacture with high-precision and control over size, porosity, and shape. In this review, we introduce a variety of tissue engineering applications to create bones, vascular, skin, cartilage, and neural structures using a variety of 3D bioprinting techniques.

3-dimensional bioprinting for tissue engineering applications.

The 3-dimensional (3D) printing technologies, referred to as additive manufacturing (AM) or rapid prototyping (RP), have acquired reputation over the past few years for art, architectural modeling, lightweight machines, and tissue engineering applications. Among these applications, tissue engineering field using 3D printing has attracted the attention from many researchers. 3D bioprinting has an advantage in the manufacture of a scaffold for tissue engineering applications, because of rapid-fabrication, high-precision, and customized-production, etc. In this review, we will introduce the principles and the current state of the 3D bioprinting methods. Focusing on some of studies that are being current application for biomedical and tissue engineering fields using printed 3D scaffolds.

Relationship between diversion colitis and quality of life in rectal cancer.

AIM: To investigated the incidence of diversion colitis (DC) and impact of DC symptoms on quality of life (QoL) after ileostomy reversal in rectal cancer. METHODS: We performed a prospective study with 30 patients who underwent low anterior resection and the creation of a temporary ileostomy for the rectal cancer between January 2008 and July 2009 at the Department of Surgery, Korea University Anam Hospital. The participants totally underwent two rounds of the examinations. At first examination, endoscopies, tissue biopsies, and questionnaire survey about the symptom were performed 3-4 mo after the ileostomy creations. At second examination, endoscopies, tissue biopsies, and questionnaire survey about the symptom and QoL were performed 5-6 mo after the ileostomy reversals. Clinicopathological data were based on the histopathological reports and clinical records of the patients. RESULTS: At the first examination, all of the patients presented with inflammation, which was mild in 15 (50%) patients, moderate in 11 (36.7%) and severe in 4 (13.3%) by endoscopy and mild in 14 (46.7%) and moderate in 16 (53.3%) by histology. At the second examination, only 11 (36.7%) and 17 (56.7%) patients had mild inflammation by endoscopy and histology, respectively. There was no significant difference in DC grade between the endoscopic and the histological findings at first or second examination. The symptoms detected on the first and second questionnaires were mucous discharge in 12 (40%) and 5 (17%) patients, bloody discharge in 5 (17%) and 3 (10%) patients, abdominal pain in 4 (13%) and 2 (7%) patients and tenesmus in 9 (30%) and 5 (17%) patients, respectively. We found no correlation between the endoscopic or histological findings and the symptoms such as mucous discharge, bleeding, abdominal pain and tenesmus in both time points. Diarrhea was detected in 9 patients at the second examination; this number correlated with the severity of DC (0%, 0%, 66.7%, 33.3% vs 0%, 71.4%, 23.8%, 4.8%, P = 0.001) and the symptom-related QoL (r = -0.791, P < 0.001). CONCLUSION: The severity of DC is related to diarrhea after an ileostomy reversal and may adversely affect QoL.

Preoperative chest computerized tomography in patients with locally advanced mid or lower rectal cancer: its role in staging and impact on treatment strategy.

OBJECTIVES: Pulmonary metastasis is frequent in rectal cancer. Some guidelines recommend chest computerized tomography (CT) for preoperative workup in rectal cancer patients, which have no solid evidence to support this recommendation. This study was designed to evaluate the role of chest CT on preoperative staging in rectal cancer patients and to assess the impact on treatment strategy. METHODS: Data were prospectively collected from 103 clinically T3/T4 mid or lower rectal cancer patients who had chest X-ray (CXR) and CT to evaluate lung metastasis. The chest images were classified into four groups: metastasis, indeterminate, benign, and negative. Patients showing indeterminate lesions had follow-up CTs at 3- to 6-month intervals. RESULTS: Nine patients (8.7%) had pulmonary metastases detected on CT. CXR did not reveal any pulmonary metastatic lesions in four of the nine patients. Of these four, treatment was changed in three patients because of these findings. Forty (38.8%) patients had indeterminate nodules on chest CT. Of these, 37 patients had follow-up CTs and four patients (10.8%) showed interval changes that were confirmed as pulmonary metastasis. CONCLUSIONS: It seems reasonable to perform chest CT for preoperative staging in patients with T3/T4 mid or lower rectal cancer.

Laparoscopic rectal resection without splenic flexure mobilization: a prospective study assessing anastomotic safety.

BACKGROUND/AIMS: It was hypothesized that a portion of the sigmoid colon and accompanying marginal artery can be preserved by omitting the complete mobilization of the splenic flexure, yet achieve safe anastomosis. This study was designed to compare the surgical safety of omitting splenic flexure mobilization during laparoscopic rectal surgery in patients with rectal cancer. METHODOLOGY: Between September 2006 and January 2008, laparoscopic rectal resection was performed in 160 consecutive patients with rectosigmoid and rectal cancer. Five patients who underwent abdominoperineal resection (APR) were excluded from this analysis. Morbidity and mortality were recorded prospectively. Splenic flexure mobilization (SFM), anastomotic leakage, bleeding, and stricture rate were analyzed in this group. RESULTS: The median operative time was 225 min. There were no operative mortalities. SFM was required in 7 patients (4.5%). Anastomotic leakage occurred in 13 patients (8.4%), anastomotic bleeding occurred in 4 patients (2.6%), and 3 patients (1.9%) had strictures. The median number of harvested lymph nodes was 19. CONCLUSIONS: A portion of the sigmoid colon can be safely used as the proximal bowel segment for anastomosis during laparoscopic rectal surgery, and thus full mobilization of the splenic flexure can be omitted.

Single-stage totally robotic dissection for rectal cancer surgery: technique and short-term outcome in 50 consecutive patients.

PURPOSE: To overcome the pitfalls of laparoscopy, a robotic system has been introduced in rectal cancer surgery. However, there is no standard procedure to maximize the advantages of the da Vinci S Surgical System. Therefore, we describe our technique of applying the robotic system during all of the steps of dissection in rectal cancer surgery and the short-term outcome. METHODS: Prospectively collected data were reviewed from 50 consecutive patients who underwent single-stage, totally robotic dissection for rectal cancer resection between July 2007 and June 2008. Robotic dissection was performed following these steps: 1) ligation of the inferior mesenteric vessels and medial to lateral dissection, 2) mobilization of the sigmoid/descending/splenic flexure colon, and 3) rectal dissection. The remaining steps including rectal transection and anastomosis were performed by a conventional laparoscopic method. RESULTS: There were 32 (64%) men and 18 (36%) women. The mean distance from the anal verge to the tumor margin was 7.3 (range, 2-13) cm. The conversion rate was 0%. The mean operative time was 304.8 (range, 190-485) minutes, and 20.6 (range, 6-48) lymph nodes were harvested. The circumferential margin was positive in one patient. The length of hospital stay after surgery was 9.2 (range, 5-24) days. Anastomotic leak rate was 8.3%, and all of the patients with leakage were managed conservatively. CONCLUSIONS: Single-stage robotic dissection for rectal cancer surgery is feasible, and its short-term outcome is acceptable. Our technique can be a suitable procedure to maximize the advantages of the da Vinci system.

Gastric adenocarcinoma after renal transplantation.

BACKGROUND/AIMS: Little is known of the characteristics of gastric adenocarcinoma after renal transplantation. This study was performed to find out the incidence and clinicopathological features of gastric adenocarcinoma after renal transplantation in an endemic area for gastric cancer. METHODOLOGY: Between April 1979 and March 2001, fourteen gastric adenocarcinoma patients (0.7%) out of 2000 renal transplant recipients in a single institute were retrospectively reviewed. RESULTS: Gastric adenocarcinoma was identified in 14 recipients (8 males and 6 females; mean age 47.6 years) about 60 months after renal transplantation. Four patients had early gastric cancer; ten patients had cancer in an advanced stage. Eleven patients underwent surgical resection, while three with distant metastasis were treated symptomatically. There was no postoperative mortality. Seven patients survived without evidence of recurrence, whereas four died of recurrence and three of gastric cancer progression. CONCLUSIONS: Renal transplant recipients are at increased risk of gastric adenocarcinoma, the most common malignancy in Korea. With curative surgery, favorable prognosis can be anticipated when the diagnosis is made at an early stage. Regular endoscopic examination for early diagnosis is recommended during the follow-up period after renal transplantation in a gastric cancer endemic area.