The bioengineering of perfusable endocrine tissue with anastomosable blood vessels.

Organ transplantation is a definitive treatment for endocrine disorders, but donor shortages limit the use of this technique. The development of regenerative therapies would revolutionize the treatment of endocrine disorders. As is the case for harvested organs, the ideal bioengineered graft would comprise vascularized endocrine tissue, contain blood vessels that could be anastomosed to host vessels, have stable blood flow, and be suitable for transplantation into various sites. Here, we describe a transplantable endocrine tissue graft that was fabricated byex vivoperfusion of tricultured cell sheets (isletß-cells, vascular endothelial cells (vECs), and mesenchymal stem cells (MSCs)) on a vascularized tissue flap ofin vivoorigin. The present study has three key findings. First, mild hypothermic conditions enhanced the success ofex vivoperfusion culture. Specifically, graft construction failed at 37 °C but succeeded at 32 °C (mild hypothermia), and endocrine tissue fabricated under mild hypothermia contained aggregations of isletß-cells surrounded by dense vascular networks. Second, the construction of transplantable endocrine tissue byex vivoperfusion culture was better achieved using a vascular flap (VF) than a muscle flap. Third, the endocrine tissue construct generated using a VF could be transplanted into the rat by anastomosis of the graft artery and vein to host blood vessels, and the graft secreted insulin into the host's circulatory system for at least two weeks after transplantation. Endocrine tissues bioengineered using these techniques potentially could be used as novel endocrine therapies.

Multi-scale vascularization strategy for 3D-bioprinted tissue using coaxial core-shell pre-set extrusion bioprinting and biochemical factors.

Three-dimensional bioprinting is a key technology in bioartificial organ production. However, production of bioartificial organs has significant limitations because it is hard to build vascular structures, especially capillaries, in printed tissue owing to its low resolution. As the vascular structure plays a critical role in delivering oxygen and nutrients to cells and removing metabolic waste, building vascular channels in bioprinted tissue is essential for bioartificial organ production. In this study, we demonstrated an advanced strategy for fabricating multi-scale vascularized tissue using a pre-set extrusion bioprinting technique and endothelial sprouting. Using a coaxial precursor cartridge, mid-scale vasculature-embedded tissue was successfully fabricated. Furthermore, upon generating a biochemical gradient environment in the bioprinted tissue, capillaries were formed in this tissue. In conclusion, this strategy for multi-scale vascularization in bioprinted tissue is a promising technology for bioartificial organ production.

Construction of a vascularized fascia-prosthesis compound model with axial pedicle for ear reconstruction surgery.

Background: To design a vascular pedicled fascia-prosthesis compound model that can be used for ear reconstruction surgery. Methods: A vascularized tissue engineering chamber model was constructed in New Zealand rabbits, and fresh tissues were obtained after 4 weeks. The histomorphology and vascularization of the newly born tissue compound were analyzed and evaluated by tissue staining and Micro-CT scanning. Results: The neoplastic fibrous tissue formed in the vascularized tissue engineering chamber with the introduction of abdominal superficial vessels, similar to normal fascia, was superior to the control group in terms of vascularization, vascular density, total vascular volume, and total vascular volume/total tissue volume. Conclusion: In vivo, introducing abdominal superficial vessels in the tissue engineering chamber prepped for ear prosthesis may form a well-vascularized pedicled fascia-prosthesis compound that can be used for ear reconstruction.

Current Strategies for Engineered Vascular Grafts and Vascularized Tissue Engineering.

Blood vessels not only transport oxygen and nutrients to each organ, but also play an important role in the regulation of tissue regeneration. Impaired or occluded vessels can result in ischemia, tissue necrosis, or even life-threatening events. Bioengineered vascular grafts have become a promising alternative treatment for damaged or occlusive vessels. Large-scale tubular grafts, which can match arteries, arterioles, and venules, as well as meso- and microscale vasculature to alleviate ischemia or prevascularized engineered tissues, have been developed. In this review, materials and techniques for engineering tubular scaffolds and vasculature at all levels are discussed. Examples of vascularized tissue engineering in bone, peripheral nerves, and the heart are also provided. Finally, the current challenges are discussed and the perspectives on future developments in biofunctional engineered vessels are delineated.

Construction of Vascularized Tissue Engineered Bone with nHA-Coated BCP Bioceramics Loaded with Peripheral Blood-Derived MSC and EPC to Repair Large Segmental Femoral Bone Defect.

The regenerative repair of segmental bone defect (SBD) is an urgent problem in the field of orthopedics. Rapid induction of angiogenesis and osteoinductivity after implantation of scaffold is critical. In this study, a unique tissue engineering strategy with mixture of peripheral blood-derived mesenchymal stem cells (PBMSC) and endothelial progenitor cells (PBEPC) was applied in a 3D-printed biphasic calcium phosphate (BCP) scaffold with highly bioactive nano hydroxyapatite (nHA) coating (nHA/BCP) to construct a novel vascularized tissue engineered bone (VTEB) for rabbit femoral SBD repair. The 2D coculture of PBMSC and PBEPC showed that they could promote the osteogenic or angiogenic differentiation of the cells from each other, especially in the group of PBEPC/PBMSC = 75:25. Besides, the 3D coculture results exhibited that the nHA coating could further promote PBEPC/PBMSC adhesion, proliferation, and osteogenic and angiogenic differentiation on the BCP scaffold. In vivo experiments showed that among the four groups (BCP, BCP-PBEPC/PBMSC, nHA/BCP, and nHA/BCP-PBEPC/PBMSC), the nHA/BCP-PBEPC/PBMSC group induced the best formation of blood vessels and new bone and, thus, the good repair of SBD. It revealed the synergistic effect of nHA and PBEPC/PBMSC on the angiogenesis and osteogenesis of the BCP scaffold. Therefore, the construction of VTEB in this study could provide a possibility for the regenerative repair of SBD.

Angiogenesis in Free-Standing Two-Vasculature-Embedded Scaffold Extruded by Two-Core Laminar Flow Device.

Rapid construction of pre-vascular structure is highly desired for engineered thick tissue. However, angiogenesis in free-standing scaffold has been rarely reported because of limitation in growth factor (GF) supply into the scaffold. This study, for the 1st time, investigated angiogenic sprouting in free-standing two-vasculature-embedded scaffold with three different culture conditions and additional GFs. A two-core laminar flow device continuously extruded one vascular channel with human umbilical vein endothelial cells (HUVECs) and a 3 mg/ml type-1 collagen, one hollow channel, and a shell layer with 2% w/v gelatin-alginate (70:30) composite. Under the GF flowing condition, angiogenic sprouting from the HUVEC vessel had started since day 1 and gradually grew toward the hollow channel on day 10. Due to the medium flowing, the HUVECs showed elongated spindle-like morphology homogeneously. Their viability has been over 80% up to day 10. This approach could apply to vascular investigation, and drug discovery further, not only to the engineered thick tissue.

Advances in hydrogel-based vascularized tissues for tissue repair and drug screening.

The construction of biomimetic vasculatures within the artificial tissue models or organs is highly required for conveying nutrients, oxygen, and waste products, for improving the survival of engineered tissues in vitro. In recent times, the remarkable progress in utilizing hydrogels and understanding vascular biology have enabled the creation of three-dimensional (3D) tissues and organs composed of highly complex vascular systems. In this review, we give an emphasis on the utilization of hydrogels and their advantages in the vascularization of tissues. Initially, the significance of vascular elements and the regeneration mechanisms of vascularization, including angiogenesis and vasculogenesis, are briefly introduced. Further, we highlight the importance and advantages of hydrogels as artificial microenvironments in fabricating vascularized tissues or organs, in terms of tunable physical properties, high similarity in physiological environments, and alternative shaping mechanisms, among others. Furthermore, we discuss the utilization of such hydrogels-based vascularized tissues in various applications, including tissue regeneration, drug screening, and organ-on-chips. Finally, we put forward the key challenges, including multifunctionalities of hydrogels, selection of suitable cell phenotype, sophisticated engineering techniques, and clinical translation behind the development of the tissues with complex vasculatures towards their future development.

Advances in tissue engineering of vasculature through three-dimensional bioprinting.

BACKGROUND: A significant challenge facing tissue engineering is the fabrication of vasculature constructs which contains vascularized tissue constructs to recapitulate viable, complex and functional organs or tissues, and free-standing vascular structures potentially providing clinical applications in the future. Three-dimensional (3D) bioprinting has emerged as a promising technology, possessing a number of merits that other conventional biofabrication methods do not have. Over the last decade, 3D bioprinting has contributed a variety of techniques and strategies to generate both vascularized tissue constructs and free-standing vascular structures. RESULTS: This review focuses on different strategies to print two kinds of vasculature constructs, namely vascularized tissue constructs and vessel-like tubular structures, highlighting the feasibility and shortcoming of the current methods for vasculature constructs fabrication. Generally, both direct printing and indirect printing can be employed in vascularized tissue engineering. Direct printing allows for structural fabrication with synchronous cell seeding, while indirect printing is more effective in generating complex architecture. During the fabrication process, 3D bioprinting techniques including extrusion bioprinting, inkjet bioprinting and light-assisted bioprinting should be selectively implemented to exert advantages and obtain the desirable tissue structure. Also, appropriate cells and biomaterials matter a lot to match various bioprinting techniques and thus achieve successful fabrication of specific vasculature constructs. CONCLUSION: The 3D bioprinting has been developed to help provide various fabrication techniques, devoting to producing structurally stable, physiologically relevant, and biologically appealing constructs. However, although the optimization of biomaterials and innovation of printing strategies may improve the fabricated vessel-like structures, 3D bioprinting is still in the infant period and has a great gap between in vitro trials and in vivo applications. The article reviews the present achievement of 3D bioprinting in generating vasculature constructs and also provides perspectives on future directions of advanced vasculature constructs fabrication.

The impact of vascularized tissue flap coverage on aortic graft infection with and without infected graft excision.

OBJECTIVES: Aortic graft infection (AGI) is a serious condition associated with a high mortality rate. However, optimal surgical options have not been identified. Therefore, we retrospectively reviewed AGI cases, including those in the thoracic and abdominal regions, with or without fistula formation, to investigate the various options for better outcomes. METHODS: We reviewed 50 patients who underwent surgical interventions for AGI out of 97 patients with arterial infective disease. The mean patient age was 67 ± 17 years. Fourteen patients (28%) had a fistula with the gastrointestinal tract or lung. A combination of graft excision and vascularized tissue flap coverage was performed in 25 cases (50%). Tissue flap alone, graft excision alone and cleansing alone were performed in 9 (18%), 10 (20%), and 6 cases (12%), respectively. RESULTS: Total in-hospital mortality rate was 32% (n = 16). In-hospital mortalities in patients with and without fistulas were 43% (6/14) and 28% (10/36), respectively (P = 0.33). Subgroup analysis among patients without fistula demonstrated that the in-hospital mortality rate of the patients with vascularized tissue flap (3/21, 14%) was significantly lower than that of the patients without vascularized tissue flap (7/14, 50%, P = 0.026). Overall 1- and 5-year survival rates were 66% and 46%, respectively. In multivariable analysis, an independent factor associated with in-hospital mortality was vascularized tissue flap (odds ratio 0.20, P = 0.024). CONCLUSIONS: Vascularized tissue flaps could provide better outcomes for AGI. Graft preservation with vascularized tissue flaps could be a useful option for AGI without fistula.

3D bioprinting and microscale organization of vascularized tissue constructs using collagen-based bioink.

Bioprinting three-dimensional (3D) tissue equivalents have progressed tremendously over the last decade. 3D bioprinting is currently being employed to develop larger and more physiologic tissues, and it is of particular interest to generate vasculature in biofabricated tissues to aid better perfusion and transport of nutrition. Having an advantage over manual culture systems by bringing together biological scaffold materials and cells in precise 3D spatial orientation, bioprinting could assist in placing endothelial cells in specific spatial locations within a 3D matrix to promote vessel formation at these predefined areas. Hence, in the present study, we investigated the use of bioprinting to generate tissue-level capillary-like networks in biofabricated tissue constructs. First, we developed a bioink using collagen type-1 supplemented with xanthan gum (XG) as a thickening agent. Using a commercial extrusion-based multi-head bioprinter and collagen-XG bioink, the component cells were spatially assembled, wherein the endothelial cells were bioprinted in a lattice pattern and sandwiched between bioprinted fibroblasts layers. 3D bioprinted constructs thus generated were stable, and maintained structural shape and form. Post-print culture of the bioprinted tissues resulted in endothelial sprouting and formation of interconnected capillary-like networks within the lattice pattern and between the fibroblast layers. Bioprinter-assisted spatial placement of endothelial cells resulted in fabrication of patterned prevascularized constructs that enable potential regenerative applications in the future.

Valve-based consecutive bioprinting method for multimaterial tissue-like constructs with controllable interfaces.

Bioprinting is a promising technology focusing on tissue manufacturing, whose vital problem is the precise assembly of multiple materials. As the primary solution, the extrusion-based multi-printhead bioprinting (MPB) method requires printhead switching during the printing process, which induces inefficient motion time and material interface defects. We present a valve-based consecutive bioprinting (VCB) method to resolve these problems, containing a precise integrated switching printhead and a well-matched voxelated digital model. The rotary valve built-in the VCB printhead guarantees the precise assembling of different materials at the interface isolated from the viscoelastic inks' elastic potential energy in the cartridge. We study the coordinated control approach of the valve rotation and pressure adjustment to achieve the seamless switching, leading to a controllable multimaterial interface, including boundary and suture structure. Furthermore, we compare the VCB method and MPB method, quantitatively and comprehensively, indicating that the VCB method obtained greater mechanical strength (maximum tensile deformation increased by 44.37%) and higher printing efficiency (effective time ratio increased by 29.48%). As an exemplar, we fabricate a muscle-like tissue with a vascular tree, suture interface encapsulating C2C12, and human dermal fibroblasts (HDFB) cells, then placed it in complete medium with continuous perfusion for 5 d. Our study suggests that the VCB method is sufficient to fabricate heterogeneous tissues with complex multimaterial interfaces.

Surgical outcome for colorectal or urinary tract-related fistula: Usefulness of vascularized tissue transfer-a retrospective study⁎.

BACKGROUND: It is challenging to manage colorectal or urinary tract-related fistula. We typically treat colorectal or urinary tract-related fistula with a vascularized tissue transfer. This study aimed to analyze the outcomes of our surgical treatments for colorectal or urinary tract-related fistula. METHODS: This retrospective review included all patients who underwent surgical repair of a colorectal or urinary tract-related fistula at our institution from October 2004 to September 2019. Patients whose surgical outcomes could not be evaluated were excluded. The primary outcome was the overall cure rate. We also evaluated the complication rate and compared the outcomes for rectovaginal fistula with those for urorectal fistula. RESULTS: The final analysis included 38 cases, of which 17 were rectovaginal fistula and 16 were urorectal fistula. The transperineal approach was used in 28 cases and transperineal and transabdominal combined in nine cases. A gracilis muscle flap was used in 19 cases and a gluteal fold flap in 13 cases. Although a major leak occurred in nine cases, the fistula was finally cured successfully in 31 cases. A comparison of the outcomes for rectovaginal fistula and urorectal fistula showed that complications occurred in 5/17 cases of rectovaginal fistula and 10/16 cases of urorectal fistula (p = 0.056). Fistulae were cured successfully in 13/17 cases of rectovaginal fistula and 14/16 cases of urorectal fistula (p = 0.656). CONCLUSION: Our surgical treatment for colorectal or urinary tract-related fistula succeeded in 31 of 38 cases. Thus, vascularized tissue transfer is useful for refractory colorectal or urinary tract-related fistula.

Novel pre-vascularized tissue-engineered dermis based on stem cell sheet technique used for dermis-defect healing.

Insufficient donor dermis and the shortage of three-dimensional vascular networks are the main limitations in the tissue-engineered dermis (TED). To solve these problems, we initially constructed pre-vascularized bone marrow mesenchymal stem cell sheet (PBMCS) and pre-vascularized fibroblasts cell sheet (PFCS) by cell sheet technology, and then superimposed or folded them together to construct a pre-vascularized TED (PTED), aiming to mimic the real dermis structure. The constructed PTED was implanted in nude mice dorsal dermis-defect wound and the wound-healing effect was quantified at Days 1, 7 and 14 via the methods of histochemistry and immunohistochemistry. The results showed that PTED could rapidly promote the wound closure, especially at Day 14, and the wound-healing rate of three-layer PTED could reach 97.2% (P < 0.01), which was faster than the blank control group (89.1%), PBMCS (92.4%), PFCS (93.8%) and six-layer PTED (92.3%). In addition, the vessel density in the PTED group was higher than the other groups on the 14th day. Taken together, it is proved that the PTED, especially three-layer PTED, is more conducive to the full-thickness dermis-defect repair and the construction of the three-dimensional vascular networks, indicating its potential application in dermis-defect repair.

Human-Recombinant-Elastin-Based Bioinks for 3D Bioprinting of Vascularized Soft Tissues.

Bioprinting has emerged as an advanced method for fabricating complex 3D tissues. Despite the tremendous potential of 3D bioprinting, there are several drawbacks of current bioinks and printing methodologies that limit  the ability to print elastic and highly vascularized tissues. In particular, fabrication of complex biomimetic structure that are entirely based on 3D bioprinting is still challenging primarily due to the lack of suitable bioinks with high printability, biocompatibility, biomimicry, and proper mechanical properties. To address these shortcomings, in this work the use of recombinant human tropoelastin as a highly biocompatible and elastic bioink for 3D printing of complex soft tissues is demonstrated. As proof of the concept, vascularized cardiac constructs are bioprinted and their functions are assessed in vitro and in vivo. The printed constructs demonstrate endothelium barrier function and spontaneous beating of cardiac muscle cells, which are important functions of cardiac tissue in vivo. Furthermore, the printed construct elicits minimal inflammatory responses, and is shown to be efficiently biodegraded in vivo when implanted subcutaneously in rats. Taken together, these results demonstrate the potential of the elastic bioink for printing 3D functional cardiac tissues, which can eventually be used for cardiac tissue replacement.

Construction of vascularized tissue-engineered bone with polylysine-modified coral hydroxyapatite and a double cell-sheet complex to repair a large radius bone defect in rabbits.

In this study, the potential of vascularized tissue-engineered bone constructed by a double cell-sheet (DCS) complex and polylysine (PLL)-modified coralline hydroxyapatite (CHA) to repair large radius bone defects was investigated in rabbits. Firstly, the DCS complex was obtained after rabbit adipose-derived mesenchymal stem cell (ADSC) culture was induced. Secondly, PLL-CHA composite scaffolds with different concentrations of PLL were prepared by the soaking and vacuum freeze-drying methods, and then the scaffolds were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, compression performance testing and cytocompatibility evaluation. Thirdly, DCS-PLL-CHA vascularized tissue-engineered bone was constructed in vitro and transplanted into a large radius bone defect model in rabbits. Finally, the potential of the DCS-PLL-CHA vascularized tissue-engineered bone to repair the large bone defect was evaluated through general observations, laser speckle imaging, scanning electron microscopy (SEM), histological staining, radiography observations and RT-PCR. The in vitro experimental results showed that the DCS complex provided a very large cell reserve, which carried a large number of osteoblasts and vascular endothelial cells that were induced in vitro. When the DCS complex was combined with the PLL-CHA scaffold in vitro, the effects of PLL on cell adhesion, proliferation and differentiation led to a situation similar to the chemotaxis of the body, making the combined complex more conducive to graft cellularization than the DCS complex alone. The in vivo experiments showed blood supply on the surface of the callus in each group, and the amount of blood perfusion on the surface of the defect area was almost equal among the groups. At 12 weeks, the surface of the DCS-PLL-CHA group was completely wrapped by bone tissue and osteoids, the cortical bone image was basically continuous, and the medullary cavity was mainly perforated. A large amount of well-arranged lamellar bone was formed, a small amount of undegraded CHA exhibited a linear pattern, and a large amount of bone filling could be seen in the pores. At 12 weeks, the expression levels of BGLAP, SPP1 and VEGF were similar in each group, but PECAM1 expression was higher in the DCS-PLL-CHA group than in the autogenous bone group and CHA group. The results showed that PLL could effectively promote the adhesion, proliferation and differentiation of ADSCs and that DCS-PLL-CHA vascularized tissue-engineered bone has potential for bone regeneration and bone reconstruction and can be used to repair large bone defects. STATEMENT OF SIGNIFICANCE: 1. PLL-CHA composite scaffolds with different concentrations of PLL were prepared by the soaking and vacuum freeze-drying methods. 2. The vascularized tissue-engineered bone was constructed by the double cell sheet (DCS) complex combined with PLL-CHA scaffolds. 3. The DCS-PLL-CHA vascularized tissue-engineered bone has potential for bone regeneration and bone reconstruction and can be used to repair large bone defects.

Macrophages significantly enhance wound healing in a vascularized skin model.

Tissue-engineered dermo-epidermal skin grafts could be applied for the treatment of large skin wounds or used as an in vitro wound-healing model. However, there is currently no skin replacement model that includes both, endothelial cells to simulate vascularization, and macrophages to regulate wound healing and tissue regeneration. Here, we describe for the first time a tissue-engineered, fully vascularized dermo-epidermal skin graft based on a fibrin hydrogel scaffold, using exclusively human primary cells. We show that endothelial cells and human dermal fibroblasts form capillary-like structures within the dermis whereas keratinocytes form the epithelial cell layer. Macrophages played a key role in controlling the number of epithelial cells and their morphology after skin injury induced with a CO2 laser. The activation of selected cell types was confirmed by mRNA analysis. Our data underline the important role of macrophages in vascularized skin models for application as in vitro wound healing models or for skin replacement therapy. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1340-1350, 2019.

Indian Subcontinent's First Bilateral Supracondylar Level Upper Limb Transplantation.

Introduction This is the first case of supracondylar level transplant from the Indian subcontinent, performed for a bilateral below elbow amputee. It has a completely different set of challenges for the transplant team, with a relatively shorter ischemia time window. The technical considerations for the same have been discussed in detail in this article. Materials and Methods The patient was a 19-year-old female who lost her both upper limbs at proximal forearm level due to severe crush injury following a road traffic accident. Insufficient bone length on either side necessitated a supracondylar level transplant. The preoperative workup included detailed clinical evaluation, biochemical, and psychological evaluation. The donor was a young brain-dead, male patient from a hospital, 30 minutes away. The donor and recipient preparations in this case were unique. The recipient's own elbow flexors and extensors were used while the elbow joint was from the donor. The specific challenges we faced during this procedure have been described in detail. Results The transplantation has been a complete technical success, with the patient rehabilitated back to her independent life style. This article describes only the technical considerations. The functional recovery aspect is part of an another soon to be published manuscript. Conclusion Supracondylar level arm-transplant requires a highly coordinated team effort with precise preoperative planning, along with meticulous attention to detail to achieve a successful outcome. In properly selected patients, it could be a life-changing procedure, worth all the effort.

A versatile perfusion bioreactor and endothelializable photo cross-linked tubes of gelatin methacryloyl as promising tools in tissue engineering.

Size and function of bioartificial tissue models are still limited due to the lack of blood vessels and dynamic perfusion for nutrient supply. In this study, we evaluated the use of cytocompatible methacryl-modified gelatin for the fabrication of a hydrogel-based tube by dip-coating and subsequent photo-initiated cross-linking. The wall thickness of the tubes and the diameter were tuned by the degree of gelatin methacryl-modification and the number of dipping cycles. The dipping temperature of the gelatin solution was adjusted to achieve low viscous fluids of approximately 0.1 Pa s and was different for gelatin derivatives with different modification degrees. A versatile perfusion bioreactor for the supply of surrounding tissue models was developed, which can be adapted to several geometries and sizes of blood-vessel mimicking tubes. The manufactured bendable gelatin tubes were permeable for water and dissolved substances, like Nile Blue and serum albumin. As a proof of concept, human fibroblasts in a three-dimensional collagen tissue model were successfully supplied with nutrients via the central gelatin tube under dynamic conditions for 2 days. Moreover, the tubes could be used as scaffolds to build-up a functional and viable endothelial layer. Hence, the presented tools can contribute to solving current challenges in tissue engineering.

Current Challenges of Bioprinted Tissues Toward Clinical Translation.

IMPACT STATEMENT: This review has a broad overview of the current challenges of bioprinted tissues towards clinical translations and future directions to overcome those challenges. The development of this field has a huge impact on the situation of an insufficient number of organ donors for life-saving organ transplantations.

Immediate Cranioplasty for Postcranioplasty Infection in Patients with Ventriculoperitoneal Shunt.

BACKGROUND: Patients with a ventriculoperitoneal (VP) shunt tend to develop epidural fluid accumulation after cranioplasty and also have a higher frequency of syndrome of the trephined after bone flap removal. Thus treatment of patients with postcranioplasty infection and a VP shunt is often challenging. CASE DESCRIPTION: We treated 2 patients with postcranioplasty infection and a VP shunt. One patient had undergone decompressive craniectomy for cerebral hemorrhage, and the other patient had a large frontal dead space following resection of a brain tumor. Both patients were treated by immediate cranioplasty with obliteration of the epidural dead space by using a vascularized free latissimus dorsi muscle flap. In both of them, the postoperative course was uneventful without any complications. CONCLUSIONS: Immediate cranioplasty and obliteration of the epidural dead space with a vascularized free latissimus dorsi muscle flap is an alternative for patients with postcranioplasty infection who are unfavorable candidates for temporary bone flap removal because of the risk of neurologic deterioration.