Surgical outcomes and prognostic factors of distal common bile duct adenocarcinoma: chronological analysis in a single high-volume institutional experience.

BACKGROUND: Distal common bile duct (dCBD) cancer is typical indication for pancreaticoduodenectomy (PD). We aimed to retrospectively evaluate surgical outcomes and investigate prognostic factors of dCBD adenocarcinoma for which PD was performed at a single institution. METHODS: We searched consecutive cases of dCBD adenocarcinoma undergone PD at Samsung Medical Center from 1995 to 2018. Cases with distant metastasis or palliative intent were excluded. The year in which the survival rate was dramatically improved was identified and entire years were divided into two periods for comparison. To balance between the two periods, we conducted propensity score matching (PSM) analysis using age, sex, body mass index (BMI), and American Society of Anesthesiologist score. RESULTS: Total of 804 cases were enrolled in this study. The entire period was divided into early period of 18 years and recent period of 6 years. The early and late period included 466 and 338 patients, respectively. As a result of PSM, balanced 316 patients were selected from each of the two periods. Significant improvements in surgical outcomes were identified, including shorter operation time, fewer blood loss, shorter hospitalization, and favorable overall survival. As results of multivariable analysis of independent risk factors for overall survival, older age and advanced N stage were identified, as expected. It was distinct that aggressive surgery and advanced tumor state in the early period and a lower BMI in the late period negatively affected the survival, respectively. CONCLUSIONS: Surgical outcomes of dCBD cancer underwent PD was improved. There were few modifiable factors to improve survival and continuous further study is needed to detect dCBD cancer in the early stages.

A 3D Printable Electroconductive Biocomposite Bioink Based on Silk Fibroin-Conjugated Graphene Oxide.

Reduced graphene oxide (rGO) has wide application as a nanofiller in the fabrication of electroconductive biocomposites due to its exceptional properties. However, the hydrophobicity and chemical stability of rGO limit its ability to be incorporated into precursor polymers for physical mixing during biocomposite fabrication. Moreover, until now, no suitable rGO-combining biomaterials that are stable, soluble, biocompatible, and 3D printable have been developed. In this study, we fabricated digital light processing (DLP) printable bioink (SGOB1), through covalent reduction of graphene oxide (GO) by glycidyl methacrylated silk fibroin (SB). Compositional analyses showed that SGOB1 contains approximately 8.42% GO in its reduced state. Our results also showed that the rGO content of SGOB1 became more thermally stable and highly soluble. SGOB1 hydrogels demonstrated superior mechanical, electroconductive, and neurogenic properties than (SB). Furthermore, the photocurable bioink supported Neuro2a cell proliferation and viability. Therefore, SGOB1 could be a suitable biocomposite for neural tissue engineering.

Silk Fibroin in Wound Healing Process.

Silk fibroin (SF), a natural bioproduct, has been extensively used in biological and biomedical fields including wound healing due to its robust biocompatibility, less immunogenic, non-toxic, non-carcinogenic, and biodegradable properties. SF in different morphologic forms, such as hydrogels, sponges, films, electrospun nanofiber mats, and hydrocolloid dressings, have been successfully used for therapeutic use as wound dressings to induce the healing process. SF has also been known to promote wound healing by increasing the cell growth, proliferation, and migration of different cells types involved in the different phase of wound healing process. In this review, we summarize the different morphologic forms of SF that have been used in the treatment of various wound healing process. We also discuss the effect of SF on various cells types during the SF-induced healing process. Furthermore, we highlight molecular signaling aspects of the SF-induced healing process.

Artificial Auricular Cartilage Using Silk Fibroin and Polyvinyl Alcohol Hydrogel.

Several methods for auricular cartilage engineering use tissue engineering techniques. However, an ideal method for engineering auricular cartilage has not been reported. To address this issue, we developed a strategy to engineer auricular cartilage using silk fibroin (SF) and polyvinyl alcohol (PVA) hydrogel. We constructed different hydrogels with various ratios of SF and PVA by using salt leaching, silicone mold casting, and freeze-thawing methods. We characterized each of the hydrogels in terms of the swelling ratio, tensile strength, pore size, thermal properties, morphologies, and chemical properties. Based on the cell viability results, we found a blended hydrogel composed of 50% PVA and 50% SF (P50/S50) to be the best hydrogel among the fabricated hydrogels. An intact 3D ear-shaped auricular cartilage formed six weeks after the subcutaneous implantation of a chondrocyte-seeded 3D ear-shaped P50/S50 hydrogel in rats. We observed mature cartilage with a typical lacunar structure both in vitro and in vivo via histological analysis. This study may have potential applications in auricular tissue engineering with a human ear-shaped hydrogel.

3D electrospun silk fibroin nanofibers for fabrication of artificial skin.

Tissue-engineered skin substitutes such as nanofibers from traditional electrospinning may offer an effective therapeutic option for the treatment of patients suffering from skin damages such as burns and diabetic ulcers. However, it is generally difficult for cells to infiltrate the nanofibers due to their small pore size and sheets-like appearance. In the present study, a facile and efficient strategy has successfully been introduced that can produce 3D silk fibroin nanofibers, obviating an intrinsic limitation of traditional and salt-leaching electrospinning by introducing cold-plate electrospinning. The cell attachment and infiltration studies indicated the use of 3D nanofiber scaffolds by cold-plate electrospinning as a potential candidate to overcome intrinsic barriers of electrospinning techniques. The 3D nanofiber scaffolds using this technique presented a high porosity with controlled thickness and an easy contouring of facial shape; these properties can contribute to the ideal candidate for artificial skin reconstruction. From the clinical editor: Electrospun nanofibers are considered as promising scaffolds for tissue engineering due to extracellular matrix mimicking factor resulting in a controllable 3D nanofibrous form. The cold-plate electrospinning technique can facilitate the fabrication of these biomaterials to create structures that could resemble the dermis.

Functional Skeletal Muscle Regeneration Using Muscle Mimetic Tissue Fabricated by Microvalve-Assisted Coaxial 3D Bioprinting.

3D-printed artificial skeletal muscle, which mimics the structural and functional characteristics of native skeletal muscle, is a promising treatment method for muscle reconstruction. Although various fabrication techniques for skeletal muscle using 3D bio-printers are studied, it is still challenging to build a functional muscle structure. A strategy using microvalve-assisted coaxial 3D bioprinting in consideration of functional skeletal muscle fabrication is reported. The unit (artificial muscle fascicle: AMF) of muscle mimetic tissue is composed of a core filled with medium-based C2C12 myoblast aggregates as a role of muscle fibers and a photo cross-linkable hydrogel-based shell as a role of connective tissue in muscles that enhances printability and cell adhesion and proliferation. Especially, a microvalve system is applied for the core part with even cell distribution and strong cell-cell interaction. This system enhances myotube formation and consequently shows spontaneous contraction. A multi-printed AMF (artificial muscle tissue: AMT) as a piece of muscle is implanted into the anterior tibia (TA) muscle defect site of immunocompromised rats. As a result, the TA-implanted AMT responds to electrical stimulation and represents histologically regenerated muscle tissue. This microvalve-assisted coaxial 3D bioprinting shows a significant step forward to mimicking native skeletal muscle tissue.

Fluidic integrated 3D bioprinting system to sustain cell viability towards larynx fabrication.

Herein, we report the first study to create a three-dimensional (3D) bioprinted artificial larynx for whole-laryngeal replacement. Our 3D bio-printed larynx was generated using extrusion-based 3D bioprinter with rabbit's chondrocyte-laden gelatin methacryloyl (GelMA)/glycidyl-methacrylated hyaluronic acid (GMHA) hybrid bioink. We used a polycaprolactone (PCL) outer framework incorporated with pores to achieve the structural strength of printed constructs, as well as to provide a suitable microenvironment to support printed cells. Notably, we established a novel fluidics supply (FS) system that simultaneously supplies basal medium together with a 3D bioprinting process, thereby improving cell survival during the printing process. Our results showed that the FS system enhanced post-printing cell viability, which enabled the generation of a large-scale cell-laden artificial laryngeal framework. Additionally, the incorporation of the PCL outer framework with pores and inner hydrogel provides structural stability and sufficient nutrient/oxygen transport. An animal study confirmed that the transplanted 3D bio-larynx successfully maintained the airway. With further development, our new strategy holds great potential for fabricating human-scale larynxes with in vivo-like biological functions for laryngectomy patients.

A digital light processing 3D-printed artificial skin model and full-thickness wound models using silk fibroin bioink.

A three-dimensional (3D) artificial skin model offers diverse platforms for skin transplantation, disease mechanisms, and biomaterial testing for skin tissue. However, implementing physiological complexes such as the neurovascular system with living cells in this stratified structure is extremely difficult. In this study, full-thickness skin models were fabricated from methacrylated silk fibroin (Silk-GMA) and gelatin (Gel-GMA) seeded with keratinocytes, fibroblasts, and vascular endothelial cells representing the epidermis and dermis layers through a digital light processing (DLP) 3D printer. Printability, mechanical properties, and cell viability of the skin hydrogels fabricated with different concentrations of Silk-GMA and Gel-GMA were analyzed to find the optimal concentrations for the 3D printing of the artificial skin model. After the skin model was DLP-3D printed using Gel-GMA 15% + Silk-GMA 5% bioink, cultured, and air-lifted for four weeks, well-proliferated keratinocytes and fibroblasts were observed in histological analysis, and increased expressions of Cytokeratin 13, Phalloidin, and CD31 were noted in immunofluorescence staining. Furthermore, full-thickness skin wound models were 3D-printed to evaluate the wound-healing capabilities of the skin hydrogel. When the epidermal growth factor (EGF) was applied, enhanced wound healing in the epidermis and dermis layer with the proliferation of keratinocytes and fibroblasts was observed. Also, the semi-quantitative reverse transcription-polymerase chain reaction revealed increased expression of Cytokeratin 13, fibroblast growth factor, and CD31 in the EGF-treated group relative to the control group. The DLP 3D-printed artificial skin model was mechanically stable and biocompatible for more than four weeks, demonstrating the potential for application in skin tissue engineering. STATEMENT OF SIGNIFICANCE: A full-thickness artificial skin model was 3D-printed in this study with a digital light processing technique using silk fibroin and gelatin, which mimics the structural and cellular compositions of the human skin. The 3D-printed skin hydrogel ensured the viability of the cells in the skin layers that proliferated well after air-lifting cultivation, shown in the histological analysis and immunofluorescence stainings. Furthermore, full-thickness skin wound models were 3D-printed to evaluate the wound healing capabilities of the skin hydrogel, which demonstrated enhanced wound healing in the epidermis and dermis layer with the application of epidermal growth factor on the wound compared to the control. The bioengineered hydrogel expands the applicability of artificial skin models for skin substitutes, wound models, and drug testing.

Three-Dimensional Digital Light-Processing Bioprinting Using Silk Fibroin-Based Bio-Ink: Recent Advancements in Biomedical Applications.

Three-dimensional (3D) bioprinting has been developed as a viable method for fabricating functional tissues and organs by precisely spatially arranging biomaterials, cells, and biochemical components in a layer-by-layer fashion. Among the various bioprinting strategies, digital light-processing (DLP) printing has gained enormous attention due to its applications in tissue engineering and biomedical fields. It allows for high spatial resolution and the rapid printing of complex structures. Although bio-ink is a critical aspect of 3D bioprinting, only a few bio-inks have been used for DLP bioprinting in contrast to the number of bio-inks employed for other bioprinters. Recently, silk fibroin (SF), as a natural bio-ink material used for DLP 3D bioprinting, has gained extensive attention with respect to biomedical applications due to its biocompatibility and mechanical properties. This review introduces DLP-based 3D bioprinting, its related technology, and the fabrication process of silk fibroin-based bio-ink. Then, we summarize the applications of DLP 3D bioprinting based on SF-based bio-ink in the tissue engineering and biomedical fields. We also discuss the current limitations and future perspectives of DLP 3D bioprinting using SF-based bio-ink.

Intraoperative Positive Pancreatic Parenchymal Resection Margin: Is It a True Indication of Completion Total Pancreatectomy after Partial Pancreatectomy for Pancreatic Ductal Adenocarcinoma?

BACKGROUND: Total pancreatectomy (TP) can be performed in cases with positive resection margin after partial pancreatectomy for pancreatic cancer. However, despite complete removal of the residual pancreatic parenchyme, it is questionable whether an actual R0 resection and favorable survival can be achieved. This study aimed to identify the R0 resection rate and postoperative outcomes, including survival, following completion TP (cTP) performed due to intraoperative positive margin. METHODS: From 1995 to 2015, 1096 patients with pancreatic ductal adenocarcinoma underwent elective pancreatectomy at the Samsung Medical Center. Among these, 25 patients underwent cTP, which was converted during partial pancreatectomy because of a positive resection margin. To compare survival after R0 resection between the cTP R0 and pancreaticoduodenectomy (PD) R0 cases, propensity score matching was conducted to balance the baseline characteristics. RESULTS: The R0 rate of cTP performed due to intraoperative positive margin was 84% (21/25). The overall 5-year survival rate (5YSR) in the 25 cTP cases was 8%. There was no difference in the 5YSR between the cTP R0 and cTP R1 groups (9.5% versus 0.0%, p = 0.963). However, the 5YSR of the cTP R0 group was significantly lower than that of the PD R0 group (9.5% versus 20.0%, p = 0.022). There was no distinct difference in postoperative complications between the cTP R0 versus cTP R1 and cTP R0 versus PD R0 groups. CONCLUSIONS: In cases with intraoperative positive pancreatic parenchymal resection margin, survival after cTP was not favorable. Careful patient selection is needed to perform cTP in such cases.

Is it worthy to perform total pancreatectomy considering morbidity and mortality?: Experience from a high-volume single center.

Total pancreatectomy (TP) is performed for diseases of the entire pancreas. However, reluctance remains regarding TP because of the fear of high morbidity and mortality. Our retrospective study aimed to evaluate the postoperative outcomes of TP performed at a high-volume single center and to identify the risk factors associated with major morbidities and mortality after TP. A total of 142 patients who underwent elective TP at Samsung Medical Center between 1995 and 2015 were included. TP was usually planned before surgery or decided during surgery [one-stage TP], and there were some completion TP cases that were performed to manage tumors that had formed in the remnant pancreas after a previous partial pancreatectomy [2-stage TP]. The differences between the 1-stage and 2-stage TP groups were analyzed. Chronological comparison was also conducted by dividing cases into 2 periods [the early and late period] based on the year TP was performed, which divided the total number of patients to almost half for each period. Among all TP patients, major morbidity occurred in 25 patients (17.6%), the rate of re-admission within 90-days was 20.4%, and there was no in-hospital and 30-days mortality. Between the 1-stage and 2-stage TP groups, most clinical, operative, and pathological characteristics, and postoperative outcomes did not differ significantly. Chronological comparison showed that, although the incidence of complications was higher, hospitalization was shorter due to advanced managements in the late period. The overall survival was improved in the late period compared to the early period, but it was not significant. A low preoperative protein level and N2 were identified as independent risk factors for major morbidity in multivariable analysis. The independent risk factors for poor overall survival were R1 resection, adenocarcinoma, and high estimated blood loss (EBL). TP is a safe and feasible procedure with satisfactory postoperative outcomes when performed at a high-volume center. More research and efforts are needed to significantly improve overall survival rate in the future.

External validation of risk prediction platforms for pancreatic fistula after pancreatoduodenectomy using nomograms and artificial intelligence.

Purpose: Postoperative pancreatic fistula (POPF) is a life-threatening complication following pancreatoduodenectomy (PD). We previously developed nomogram- and artificial intelligence (AI)-based risk prediction platforms for POPF after PD. This study aims to externally validate these platforms. Methods: Between January 2007 and December 2016, a total of 1,576 patients who underwent PD in Seoul National University Hospital, Ilsan Paik Hospital, and Boramae Medical Center were retrospectively reviewed. The individual risk scores for POPF were calculated using each platform by Samsung Medical Center. The predictive ability was evaluated using a receiver operating characteristic curve and the area under the curve (AUC). The optimal predictive value was obtained via backward elimination in accordance with the results from the AI development process. Results: The AUC of the nomogram after external validation was 0.679 (P < 0.001). The values of AUC after backward elimination in the AI model varied from 0.585 to 0.672. A total of 13 risk factors represented the maximal AUC of 0.672 (P < 0.001). Conclusion: We performed external validation of previously developed platforms for predicting POPF. Further research is needed to investigate other potential risk factors and thereby improve the predictability of the platform.

Silk Fibroin-Based Biomaterials for Hemostatic Applications.

Hemostasis plays an essential role in all surgical procedures. Uncontrolled hemorrhage is the primary cause of death during surgeries, and effective blood loss control can significantly reduce mortality. For modern surgeons to select the right agent at the right time, they must understand the mechanisms of action, the effectiveness, and the possible adverse effects of each agent. Over the past decade, various hemostatic agents have grown intensely. These agents vary from absorbable topical hemostats, including collagen, gelatins, microfibrillar, and regenerated oxidized cellulose, to biologically active topical hemostats such as thrombin, biological adhesives, and other combined agents. Commercially available products have since expanded to include topical hemostats, surgical sealants, and adhesives. Silk is a natural protein consisting of fibroin and sericin. Silk fibroin (SF), derived from silkworm Bombyx mori, is a fibrous protein that has been used mostly in fashion textiles and surgical sutures. Additionally, SF has been widely applied as a potential biomaterial in several biomedical and biotechnological fields. Furthermore, SF has been employed as a hemostatic agent in several studies. In this review, we summarize the several morphologic forms of SF and the latest technological advances on the use of SF-based hemostatic agents.

Biocompatible fluorescent silk fibroin bioink for digital light processing 3D printing.

Chemically modified silk fibroin (SF) bioink has been used for three-dimensional (3D) bioprinting in tissue engineering because of its biocompatibility and printability. Also, fluorescent silk fibroin (FSF) from transgenic silkworms has been recently applied in biomedicine because of its fluorescence property. However, the fabrication of fluorescent hydrogel from FSF has not been elucidated. In this study, we showed the fabrication of a digital light processing (DLP) printable bioink from a chemically modified FSF. This bioink was fabricated by covalent conjugation of FSF and glycidyl methacrylate (GMA) and can be printed into various structures, such as the brain, ear, hand, lung, and internal organs. The physical properties of glycidyl methacrylated fluorescent silk fibroin (FSGMA) hydrogel was like the glycidyl methacrylated non-fluorescent silk fibroin (SGMA) hydrogel. The FSGMA hydrogel significantly retains its fluorescence property and has excellent biocompatibility. All these properties make FSGMA hydrogel a potent tool in encapsulated cell tracking and observing the scaffolds' degradation in vivo. This study suggested that our 3D DLP printable FSF bioink could play a promising role in the biomedical field.

Reduction of inferior orbital wall fractures using a Foley catheter and an Endoloop.

BACKGROUND: Various surgical approaches have been used to treat orbital blowout fractures. Among them, the transnasal endoscopic approach avoids external scars and allows clear observation of the fracture site. We conducted a retrospective study of blowout fractures reduced using a Foley catheter and an Endoloop. METHODS: Patients (n=24) who underwent endoscopic reduction of inferior orbital wall fractures were analyzed. They were diagnosed using 3-mm facial computed tomography, and the surgical treatment consisted of fracture reduction using Foley catheter and Endoloop. Postoperatively, they were followed up for at least 3 months. RESULTS: There was no significant intraoperative or postoperative complication. The symptoms in all but two patients resolved completely after surgery. CONCLUSION: The technique using Foley catheter and Endoloop to reduce inferior orbital wall fractures endoscopically is safe and efficacious.

A balloon dilatation technique for the treatment of intramaxillary lesions using a Foley catheter in chronic maxillary sinusitis.

BACKGROUND: In chronic maxillary sinusitis, pathologic mucosas of the anterior and lateral walls of the maxillary sinus are difficult to remove. Trocar insertion to the canine fossa is the most commonly used procedure. In the present work, we report a method involving a balloon dilatation technique for treatment of intramaxillary lesions using a Foley catheter in chronic maxillary sinusitis and the outcomes of this approach. METHODS: Records of 34 patients with intramaxillary sinus lesions who underwent endoscopic sinus surgery were analyzed. After widening the natural ostium, a 10F Foley catheter was inserted through the widening ostium into the maxillary sinus. The intramaxillary lesion was removed by repeated balloon inflation and deflation of the Foley catheter. The patients were followed-up for at least 6 months after the surgery. RESULTS: There were no significant intraoperative or postoperative complications. We found that the postoperative symptoms and resolution of the lesions in comparison to classic functional endoscopic sinus surgery were not different in authors' experiences. CONCLUSION: The balloon dilatation technique using a Foley catheter is a minimally invasive and effective technique that is not associated with major complications in cases of intramaxillary lesions.

A digital light processing 3D printed magnetic bioreactor system using silk magnetic bioink.

Among various bioreactors used in the field of tissue engineering and regenerative medicine, a magnetic bioreactor is more capable of providing steady force to the cells while avoiding direct manipulation of the materials. However, most of them are complex and difficult to fabricate, with drawbacks in terms of consistency and biocompatibility. In this study, a magnetic bioreactor system and a magnetic hydrogel were manufactured by single-stage three-dimensional (3D) printing with digital light processing (DLP) technique for differentiation of myoblast cells. The hydrogel was composed of a magnetic part containing iron oxide and glycidyl-methacrylated silk fibroin, and a cellular part printed by adding mouse myoblast cell (C2C12) to gelatin glycidyl methacrylate, that was placed in the magnetic bioreactor system to stimulate the cells in the hydrogel. The composite hydrogel was steadily printed by a one-stage layering technique using a DLP printer. The magnetic bioreactor offered mechanical stretching of the cells in the hydrogel in 3D ways, so that the cellular differentiation could be executed in three dimensions just like the human environment. Cell viability, as well as gene expression using quantitative reverse transcription-polymerase chain reaction, were assessed after magneto-mechanical stimulation of the myoblast cell-embedded hydrogel in the magnetic bioreactor system. Comparison with the control group revealed that the magnetic bioreactor system accelerated differentiation of mouse myoblast cells in the hydrogel and increased myotube diameter and lengthin vitro. The DLP-printed magnetic bioreactor and the hydrogel were simply manufactured and easy-to-use, providing an efficient environment for applying noninvasive mechanical force via FDA-approved silk fibroin and iron oxide biocomposite hydrogel, to stimulate cells without any evidence of cytotoxicity, demonstrating the potential for application in muscle tissue engineering.

Treatment of Fungal-Infected Diabetic Wounds with Low Temperature Plasma.

Diabetes mellitus renders patients susceptible to chronic wounds and various infections. Regarding the latter, fungal infections are of particular concern since, although they are the source of significant morbidity and mortality in immunocompromised patients, they are generally resistant to conventional treatment and a definite treatment strategy has not yet been established. Herein, we report the treatment of skin wounds in a diabetic rat model, infected by Candida albicans, with low temperature helium plasma generated in a hand-held atmospheric jet device. A fungal infection was induced on two dorsal skin wounds of the diabetic rats, and one wound was treated with the plasma jet whereas the other served as a control. Histological analysis revealed accelerated skin wound healing and decreased evidence of fungal infection in the plasma-treated group, as compared to the control group. Regeneration of the epidermis and dermis, collagen deposition, and neovascularization were all observed as a result of plasma treatment, but without wound contraction, scar formation or any evidence of thermal damage to the tissue. These findings demonstrate that the He plasma jet is remarkably effective in diabetic skin wounds infected by Candida albicans, thereby providing a promising medical treatment option for diabetes mellitus patients with skin wound and fungal infections.

3D bioprinted silk fibroin hydrogels for tissue engineering.

The development of biocompatible and precisely printable bioink addresses the growing demand for three-dimensional (3D) bioprinting applications in the field of tissue engineering. We developed a methacrylated photocurable silk fibroin (SF) bioink for digital light processing 3D bioprinting to generate structures with high mechanical stability and biocompatibility for tissue engineering applications. Procedure 1 describes the synthesis of photocurable methacrylated SF bioink, which takes 2 weeks to complete. Digital light processing is used to fabricate 3D hydrogels using the bioink (1.5 h), which are characterized in terms of methacrylation, printability, mechanical and rheological properties, and biocompatibility. The physicochemical properties of the bioink can be modulated by varying photopolymerization conditions such as the degree of methacrylation, light intensity, and concentration of the photoinitiator and bioink. The versatile bioink can be used broadly in a range of applications, including nerve tissue engineering through co-polymerization of the bioink with graphene oxide, and for wound healing as a sealant. Procedure 2 outlines how to apply 3D-printed SF hydrogels embedded with chondrocytes and turbinate-derived mesenchymal stem cells in one specific in vivo application, trachea tissue engineering, which takes 2-9 weeks.

Reinforced-hydrogel encapsulated hMSCs towards brain injury treatment by trans-septal approach.

Encapsulated stem cells in various biomaterials have become a potentially promising cell transplantation strategy in the treatment of various neurologic disorders. However, there is no ideal cell delivery material and method for clinical application in brain diseases. Here we show silk fibroin (SF)-based hydrogel encapsulated engineered human mesenchymal stem cells (hMSCs) to overproduce brain-derived neurotrophic factor (BDNF) (BDNF-hMSC) is an effective approach to treat brain injury through trans-septal cell transplantation in the rat model. In this study, we observed SF induced sustained BDNF production by BDNF-hMSC both in 2D (9.367 ± 1.969 ng/ml) and 3D (7.319 ± 0.1025 ng/ml) culture conditions for 3 days. Through immunohistochemistry using α-tubulin, BDNF-hMSCs showed a significant increased average neurite length of co-cultured neuro 2a (N2a) cells, suggested that BDNF-hMSCs induced neurogenesis in vitro. Encapsulated BDNF-hMSC, pre-labeled with the red fluorescent dye PKH-26, exhibited intense fluorescence up to 14 days trans-septal transplantation, indicated excellent viability of the transplanted cells. Compared to the vehicle-treated, encapsulated BDNF- hMSC demonstrated significantly increased BDNF level both in the sham-operated and injured hippocampus (Hip) through immunoblot analysis after 7 days implantation. Transplantation of the encapsulated BDNF-hMSC promoted neurological functional recovery via significantly reduced neuronal death in the Hip 7 days post-injury. Using magnetic resonance imaging (MRI) analysis, we demonstrated that encapsulated BDNF-hMSC reduced lesion area significantly at 14 and 21 days in the damaged brain following trans-septal implantation. This stem cell transplantation approach represents a critical set up towards brain injury treatment for clinical application.