Tissue Bioengineering Research Articles

Host non-inflammatory neutrophils mediate the engraftment of bioengineered vascular networks.

Notwithstanding remarkable progress in vascular network engineering, implanted bioengineered microvessels largely fail to form anastomoses with the host vasculature. Here, we demonstrate that implants containing assembled human vascular networks (A-Grafts) fail to engraft due to their inability to engage non-inflammatory host neutrophils upon implantation into mice. In contrast, unassembled vascular cells (U-Grafts) readily engage alternatively polarized neutrophils, which in turn serve as indispensable mediators of vascular assembly and anastomosis. The depletion of host neutrophils abrogated vascularization in U-Grafts, whereas an adoptive transfer of neutrophils fully restored vascularization in myeloid-depleted mice. Neutrophil engagement was regulated by secreted factors and was progressively silenced as the vasculature matured. Exogenous addition of factors from U-Grafts reengaged neutrophils and enhanced revascularization in A-Grafts, a process that was recapitulated by blocking Notch signaling. Our data suggest that the pro-vascularization potential of neutrophils can be harnessed to improve the engraftment of bioengineered tissues.

Fabrication of micro-alginate gel tubes utilizing micro-gelatin fibers

Tissues engineered utilizing biofabrication techniques have recently been the focus of much attention, because these bioengineered tissues have great potential to improve the quality of life of patients with various hard-to-treat diseases. Most tissues contain micro-tubular structures including blood vessels, lymphatic vessels, and bile canaliculus. Therefore, we bioengineered a micro diameter tube using alginate gel to coat the core gelatin gel. Micro-gelatin fibers were fabricated by the coacervation method and then coated with a very thin alginate gel layer by dipping. A micro diameter alginate tube was produced by dissolving the core gelatin gel. Consequently, these procedures led to the formation of micro-alginate gel tubes of various shapes and sizes. This biofabrication technique should contribute to tissue engineering research fields.

COMPARATIVE ANALYSIS OF IMMUNOLOGICAL COMPATIBILITY OF BIOACTIVE CALCIUM PHOSPHATE COATINGS ON TITANIUM AND MAGNESIUM ALLOYS

Current strategies for developing the biomaterials suggest passive modulation of osteoinductive and osteoconductive properties of the implant surface through a change in their physical and chemical parameters. Also, the osseointegration of implant depends on the reaction of the immune system, the severity of which is determined by physical and chemical properties of the material and the morphological features of the coating. In this paper, the plasma electrolytic oxidation (PEO) method for the formation of biologically active compositional corrosion resistant calcium phosphate coatings on titanium BT1-0 and magnesium alloy MA8, designed for bone bioengineering was used. Bioactive PEO coatings were additionally treated with superdispersed polytetrafluoroethylene (SPTFE) in order to improve anti-corrosion properties. The cellular and molecular aspects of immunological compatibility of bioactive calcium phosphate coatings formed on titanium and magnesium alloys by promising technology of plasma electrolytic oxidation and intended for bone tissue bioengineering were studied. It is shown that PEO coatings formed on titanium and magnesium induce an activation of human peripheral blood leukocytes in vitro, associated with increased expression of activation of molecules of CD69, CD38, CD11b on the cell membranes while shedding L-selectin (CD62L). Influence of coating process technologies on the intensity of the activation processes was established. Contact cells with calcium-phosphate PEO coatings formed on titanium and magnesium alloys induced a less pronounced activation in comparison with the untreated implants. The minimal reaction of the cells of the innate immunity was observed at using a composite of PEO coatings with SPTFE, obtained by electrophoretic deposition. The composite coating on magnesium alloys induces response of the cells of the innate immunity, comparable with the response to the coatings on titanium alloys. On the whole, immunological characteristics of the PEO coatings on titanium BT1-0 and magnesium alloy of MA8 demonstrate possibility of development of materials and wares for implant surgery, including bioresorbable alloys on magnesium base. For citation:Zaporozhets T.S., Puz A.V., Sinebryukhov S.L., Gnedenkov S.V., Smolina T.P., Gazha A.K. Comparative analysis of immunological compatibility of bioactive calcium phosphate coatings on titanium and magnesium alloys. Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol. 2017. V. 60. N 2. P. 45-51.

Uterus transplantation and beyond

Uterus transplantation is today the only available treatment for absolute uterine factor infertility which is caused by either congenital/surgical uterine absence or that a present uterus is non-functioning. Structured animal-based research, from rodents to nonhuman primates, was the scientific basis for a successful introduction of uterus transplantation as a clinical procedure. The patient groups for uterus transplantation, the preclinical research and data from the published human cases will be covered herein. During recent years the concept of bioengineering of organs and tissues has emerged. Creation of a bioengineered uterus is in the initial research state, with experiments performed in rodents. The research that has been performed to create a bioengineered uterus will be summarized. In conclusion, uterus transplantation is now a clinical experimental procedure for treatment of uterine factor infertility. In parallel to the establishment of this combined assisted reproduction technique and transplantation procedure as a routine clinical procedure, we predict that uterus bioengineering will develop further towards introduction within the human setting, but that this process will take several years.

Effects of strontium ranelate treatment on osteoblasts cultivated onto scaffolds of trabeculae bovine bone.

Blocks of Bovine bone have shown promising results as implantable scaffolds to promote bone regeneration. Strontium ranelate (SrR) is both an antiresorptive and an anabolic drug that has been indicated for oral administration to treat osteoporosis. Few studies, however, have investigated the local effects of SrR and its use in association with biomaterials thus far. In this work, we investigated SrR effects in cultures of primary osteoblasts (PO, from Wistar rats calvaria) and immortalized osteoblasts (IO, from MC3T3-E1 cell line) cultivated as a monolayer or in association with scaffolds of bovine bone in mineralized (MBB) and demineralized (DBB) forms. The optimum dose to induce SrR effects on cell viability was established as 0.1mM. Our results suggested that the local administration of SrR is biocompatible and non-cytotoxic. In addition, SrR appeared to accelerate primary osteoblast cell differentiation by enhancing alkaline phosphatase activity, the expression of osteogenic differentiation markers, the synthesis of the organic matrix, and a decrease of Ca2+ ions in mineralized nodules. DBB was found to be a better scaffold material to promote PO and IO cell proliferation. Exposing the proteins of the demineralized bone matrix might improve scaffold osteoconductive properties. Our results indicated the importance of further investigation of the administration of SrR at sites of bone repair. The association of SrR and bone grafts suggests the possibility of using SrR as a co-adjuvant for bone tissue bioengineering and in bone regeneration therapies.

Biomaterials innovation for next generation exvivo immune tissue engineering.

Primary and secondary lymphoid organs are tissues that facilitate differentiation of B and T cells, leading to the induction of adaptive immune responses. These organs are present in the body from birth and are also recognized as locations where self-reactive B and T cells can be eliminated during the natural selection process. Many insights into the mechanisms that control the process of immune cell development and maturation in response to infection come from the analysis of various gene-deficient mice that lack some or all hallmark features of lymphoid tissues. The complexity of such animal models limits our ability to modulate the parameters that control the process of immune cell development, differentiation, and immunomodulation. Engineering functional, living immune tissues using biomaterials can grant researchers the ability to reproduce immunological events with tunable parameters for more rapid development of immunotherapeutics, cell-based therapy, and enhancing our understanding of fundamental biology as well as improving efforts in regenerative medicine. Here the author provides his review and perspective on the bioengineering of primary and secondary lymphoid tissues, and biomaterials innovation needed for the construction of these immune organs in tissue culture plates and on-chip.

Essential design considerations for the resazurin reduction assay to noninvasively quantify cell expansion within perfused extracellular matrix scaffolds.

Precise measurement of cellularity within bioartificial tissues and extracellular matrix (ECM) scaffolds is necessary to augment rigorous characterization of cellular behavior, as accurate benchmarking of tissue function to cell number allows for comparison of data across experiments and between laboratories. Resazurin, a soluble dye that is reduced to highly fluorescent resorufin in proportion to the metabolic activity of a cell population, is a valuable, noninvasive tool to measure cell number. We investigated experimental conditions in which resazurin reduction is a reliable indicator of cellularity within three-dimensional (3D) ECM scaffolds. Using three renal cell populations, we demonstrate that correlation of viable cell numbers with the rate of resorufin generation may deviate from linearity at higher cell densities, lower resazurin working volumes, or longer incubation times that all contribute to depleting the pool of resazurin. In conclusion, while the resazurin reduction assay provides a powerful, noninvasive readout of metrics enumerating cellularity and growth within ECM scaffolds, assay conditions may strongly influence its applicability for accurate quantification of cell number. The approach and methodological recommendations presented herein may be used as a guide for application-specific optimization of this assay to obtain rigorous and accurate measurement of cellular content in bioengineered tissues.

3D bioengineered tissues: From advancements in in vitro safety to new horizons in disease modeling.

Research aimed at more fully emulating human biology in vitro has rapidly progressed in recent years with advancements in 3D tissue engineering and microphysiological systems. The initial target of such systems has been directed towards drug and chemical safety assessment, with the goal of improving sensitivity and predictive capabilities. Here we discuss recent developments of in vitro organ culture systems, and their future applications in modeling human disease.

Emerging Biomaterials in Trauma.

Emerging technologies and research into the science of biomaterials have developed exponentially and provide facial reconstructive surgeons with a plethora of options for a multitude of varying presentations. This article presents a comprehensive discussion in the ever-evolving field of material science and emerging biomaterials. A complete understanding of the current status of such materials is necessary for the appropriate incorporation and applicability to adequate clinical situations. The rapid progress seen in biomaterials is evidenced through the forward direction of bioengineered tissues, the incorporation of growth factors in varying scenarios, and the unique characteristics of 3-D printing of patient specific scaffolds.

The Current Use of Stem Cells in Bladder Tissue Regeneration and Bioengineering.

Many pathological processes including neurogenic bladder and malignancy necessitate bladder reconstruction, which is currently performed using intestinal tissue. The use of intestinal tissue, however, subjects patients to metabolic abnormalities, bladder stones, and other long-term sequelae, raising the need for a source of safe and reliable bladder tissue. Advancements in stem cell biology have catapulted stem cells to the center of many current tissue regeneration and bioengineering strategies. This review presents the recent advancements in the use of stem cells in bladder tissue bioengineering.

Efficient biomaterials for tissue engineering of female reproductive organs.

Current investigations on the bioengineering of female reproductive tissues have created new hopes for the women suffering from reproductive organ failure including congenital anomaly of the female reproductive tract or serious injuries. There are many surgically restore forms that constitute congenital anomaly, however, to date, there is no treatment except surgical treatment of transplantation for patients who are suffering from anomaly or dysfunction organs like vagina and uterus. Restoring and maintaining the normal function of ovary and uterus require the establishment of biological substitutes that can cover the roles of structural support for cells and passage of secreting molecules. As in the case of constructing other functional organs, reproductive organ manufacturing also needs biological matrices which can provide an appropriate condition for attachment, growth, proliferation and signaling of various kinds of grafted cells. Among the organs, uterus needs special features such as plasticity due to their amazing changes in volume when they are in the state of pregnancy. Although numerous natural and synthetic biomaterials are still at the experimental stage, some biomaterials have already been evaluated their efficacy for the reconstruction of female reproductive tissues. In this review, all the biomaterials cited in recent literature that have ever been used and that have a potential for the tissue engineering of female reproductive organs were reviewed, especially focused on bioengineered ovary and uterus.

Establishment of a tumour-stroma airway model (OncoCilAir) to accelerate the development of human therapies against lung cancer.

This paper highlights the work for which OncoTheis, a Swiss biotechnology company, engaged in the development of innovative bioengineered tissues and organoids for cancer research, was co-awarded the 2015 Lush Science Prize. Noting that the use of animal models failed to lead to the design of effective treatments for cancer, OncoTheis has opted to develop in vitro models based exclusively on human cells. The company currently focuses on lung cancer, which is the leading cause of cancer-related deaths worldwide, with more than one million deaths per year. To address this public health concern, we developed OncoCilAir™, a new 3-D model that mimics in vitro the progression of the disease as it happens in patients. In this system, bronchial and lung tumour cells obtained from discarded surgical tissue are cocultured in a Petri dish to reconstitute a fragment of the human lung. After appropriate differentiation, the culture closely reproduces malignant pulmonary nodules invading a small piece of functional airway tissue. As OncoCilAir includes both healthy and cancerous tissues, it can be used to test tumour-killing activity and the adverse effects of chemotherapies and other anti-cancer drugs. Moreover, a single culture can be maintained for up to three months, which permits studies of longer-term effects, including the assessment of drug resistance and tumour recurrence. OncoCilAir heralds a new generation of integrated in vitro models, which is expected to increase the quality of preclinical research while replacing animal testing.

Tissue Bioengineering in the Treatment of Osteochondritis Dissecans of the Talus in Children With Open Physis: Preliminary Results.

Juvenile osteochondritis dissecans of the talus (JOCDT) is a focal idiopathic lesion primarily of the subchondral bone leading to subsequent cartilaginous damage. The majority of the papers dealing with JOCDT reported heterogeneous case studies of patients treated with different cartilage repair techniques. The purpose of this paper is to retrospectively review both clinical and radiologic results among 7 patients affected by JOCDT treated with arthroscopic bone marrow aspirate concentrate (BMAC) transplantation with the 1-step technique. Both standard anterior-posterior and lateral radiographs and a 1.5 T magnetic resonance imaging of the affected ankle were preoperatively performed in all the patients. The American Orthopaedic Foot and Ankle Society (AOFAS) score and the visual analogue scale were administered to the patients preoperatively and at the final follow-up. Patients were followed up to an average of 48.1±18.4 months. According to the Berndt and Harty classification, 6 lesions were found to be in stage III and 1 lesion in stage IV. The average preoperative AOFAS score was 58.8±7.6 points. At the mean follow-up of 48.1 months the average AOFAS score improved to 95.7±5.4 points (P<0.05). Visual analogue scale improved from 6.3 preoperatively to 0.4 at final follow-up (P<0.05). Complete radiographic healing, in terms of complete bony filling, was observed in 3 of 7 cases. The magnetic resonance imaging analysis showed a complete filling of the osteochondral defect in 4 patients, whereas in 1 patient a hypotrofic tissue was observed. BMAC transplantation is able to provide good to excellent results in the treatment of JOCDT. The 43% of our patients showed a complete radiographic healing, but all the patients were satisfied with the procedure. Because of the rareness of the lesion, further studies involving more patients and with a longer follow-up are required, to establish the advantage of performing a regenerative procedure like the BMAC transplantation in a pediatric population. Level IV.

Cardiac fibroblast-derived VCAM-1 enhances cardiomyocyte proliferation for fabrication of bioengineered cardiac tissue.

BackgroundFibroblasts are indispensable for the fabrication of cell-sheet–based bioengineered cardiac tissues; however, whether cardiac fibroblasts can improve tissue properties for transplantation or in vitro models compared with other fibroblast types remains unclear. We compared the cell organization and functional properties of cardiomyocyte sheets derived from co-culture with different fibroblast types and investigated the molecular mechanisms for the observed differences.Methods and resultsCardiac cell sheets were fabricated by co-culturing mouse embryonic stem cell (ESC)-derived cardiomyocytes with mouse neonatal cardiac fibroblasts (NCFs), mouse adult cardiac fibroblasts (ACFs), and mouse adult dermal fibroblasts (ADFs). Cardiac cell sheets obtained from NCF or ACF co-culture showed numerous uniformly distributed and functional (beating) cardiomyocytes, while cell sheets obtained by co-culture with ADFs showed fewer and aggregated cardiomyocytes. The greater number of cardiomyocytes in the presence of NCFs was because of enhanced cardiomyocyte proliferation, as revealed by protein markers of mitosis and BrdU incorporation. Microarray analysis revealed that NCFs expressed substantially higher levels of vascular cell adhesion molecule-1 (VCAM-1) than ADFs. Treatment of ESC-derived cardiomyocytes in monoculture with soluble VCAM-1 significantly increased the number of functional cardiomyocytes, while the enhancement of cardiomyocyte number by co-culture with NCFs was abolished by anti-VCAM-1 antibodies.ConclusionsCardiac fibroblasts enhance the proliferation of ESC-derived cardiomyocytes through VCAM-1 signaling, leading to an increase in functional myocardial cells in bioengineered tissue sheets. These sheets may be advantageous for cell-based therapy and in vitro heart research.

Laminin-111 Peptides Conjugated to Fibrin Hydrogels Promote Formation of Lumen Containing Parotid Gland Cell Clusters.

Previous studies showed that mouse submandibular gland cells form three-dimensional structures when grown on Laminin-111 gels. The use of Laminin-111 for tissue bioengineering is complicated due to its lack of purity. By contrast, the use of synthetic peptides derived from Laminin-111 is beneficial due to their high purity and easy manipulation. Two Laminin-111 peptides have been identified for salivary cells: the A99 peptide corresponding to the α1 chain from Laminin-111 and the YIGSR peptide corresponding to the β1 chain from Laminin-111, which are important for cell adhesion and migration. We created three-dimensional salivary cell clusters using a modified fibrin hydrogel matrix containing immobilized Laminin-111 peptides. Results indicate that the YIGSR peptide improved morphology and lumen formation in rat parotid Par-C10 cells as compared to cells grown on unmodified fibrin hydrogel. Moreover, a combination of both peptides not only allowed the formation of functional three-dimensional salivary cell clusters but also increased attachment and number of cell clusters. In summary, we demonstrated that fibrin hydrogel decorated with Laminin-111 peptides supports attachment and differentiation of salivary gland cell clusters with mature lumens.

A fast, reliable and cost-effective method to generate tumor organs for therapy screening in vivo

Innovative anticancer treatments continuously require tissue bioengineering models to test novel therapies. The increasing number of developments based on nanotechnology for cancer therapy or theragnostics demand simple, reliable, fast and cost-effective cancer in vivo models for preclinical testing. However, despite the many tumor models available, very few reproduce the complex intratumoral cell-to-cell interactions as well as the accompanying systemic whole body effects resulting of the tumor organ metabolic, hormonal or growth factor activities, all having critical implications in the success of cancer therapies. Here we describe a reliable tumor model that can be easily reproduced to generate visible solid malignant melanoma tumor organs within a defined period of 5–10 days recapitulating the tumor stroma that is essential for cancer development. These models can be easily evaluated in vivo or by anatomo-pathological procedures. This method provides a fast, reproducible, reliable and cost-effective way to generate solid tumors for in vivo therapy, drug, nanomaterial or imaging probe evaluation, diagnostic or theragnostic screening and validation.

Impact of Storage at -80°C on Encapsulated Liver Spheroids After Liquid Nitrogen Storage.

For many bioengineered tissues to have practical clinical application, cryopreservation for use on demand is essential. This study examined different thermal histories on warming and short holding periods at different subzero temperatures on subsequent functional recoveries of alginate encapsulated liver spheroids (ELS) for use in a bioartificial liver device. This mimicked transport at liquid nitrogen (−196°C) or dry ice (∼−80°C) temperatures. Holding at −80°C on warming after −196°C storage resulted in ELS expressing significant (p < 0.001) damage compared with direct thaw from liquid nitrogen, with viable cell number falling from 74.0 ± 8.4 million viable cells/mL without −80°C storage to 1.9 ± 0.6 million viable cells/mL 72 h post-thaw after 8 days storage at −80°C. Even 1 day at −80°C after −196°C storage resulted in lower viability (down 21% 24 h post-thaw), viable cell count (down 29% 24 h post-thaw), glucose, and alpha-1-fetoprotein production (reduced by 59% and 95% 24 h from 1 day post-thaw, respectively). Storage at −80°C was determined to be harmful only during the warming cycle. Chemical measurements of the alginate component of ELS were unchanged by cryogenic exposure in either condition.

Contribution of Hypertrophic Chondrocytes to the Homeostasis of Annulus Fibrosis in Normal and Degenerative Intervertebral Discs

Introduction Annulus fibrosis (AF) is a lamellar structure surround the central nucleus pulposus (NP) in the interverterbral discs, the outer AF composed of fibroblast-like cells and anchored to the bone of the vertebral body and the cells within inner AF (iAF) is more chondrogenic and the lamellae are anchored onto the cartilage endplate (cEP). From histology of human, rabbit and mouse IVDs, there appears to be a continuum of cells invading from cEP to iAF. Degenerative conditions such as compressive loading may lead to cell death in AF, however, how the cells are replenished in the damaged tissue is not understood. Using genetic tools in mice, we show that hypertrophic chondrocytes (HCs) in the cEP are a source of iAF cells in postnatal life of mouse and in repair processes following static compression of the disc. Material and Methods Cell lineage tracing in mice was performed using a tamoxifen-inducible Cre recombinase (CreERT) under the regulation of the endogenous Col10a1 promoter with specific expression in HCs in the cEP. When crossed with Rosa26lacZ reporter mice, a single dose of tamoxifen injection will labeled a specific pool of HCs and their date followed in vivo. Snail2, Twist1, E47-E2A and Tgfb2 (genes in the EMT pathway) were analyzed by immunohistochemistry. For static compression, tail of 8-week-old Col10a1-Cre; ROSA-tdTomato double mutant mice were bend laterally, the distal coccyx (level 13) was affix with the proximal coccyx (level 5) forming a loop and maintained for 5 weeks to apply an asymmetrical loading to the discs. Apoptosis were detected with the TUNEL assay and the HC-descendent cells (tdTomato+) were visualized with fluorescent imaging. Results One week after injection of tamoxifen to Col10a1-CreERT; Rosa26lacZ mice, only round cells (HCs) in the cEP were detected to be lacZ+, no cells in the iAF was labeled. Three weeks after injection, flattened lacZ positive cells were detected in the iAF, indicating these cells are originated from the cEP. These cells become more migratory, with rearrange cytoskeletal structure, becoming flattened cells and reside within the iAF. These cellular morphological changes are consistent with the criteria of EMT that are involved in various developmental processes and key markers such as Snail2, and Twist1 are all positive to the cells undergoing this HC-iAF transition. In the asymmetric tail-looping model, robust apoptosis of iAF cells was detected in the compressive side but not the extended side after 5 weeks of looping. More HC-descendent cells (tdTomato+) transited from the cEP to the iAF compare with the control disc without looping during the compression period. Conclusion We demonstrated that HCs in cEP act continuously as the progenitor cells contributing to the iAF during normal development. We showed an EMT-like mechanism might be involved to this HC-iAF transition. Mechanical compression but not distention induces cell death in the AF, but more HC transit to iAF as part of the repair process in the unlooping period. Thus, HCs in the cEP may act as source of progenitor cells for iAF. Understanding the differentiation of these cells will provide valuable information for therapeutically treatment for disc repair or bioengineering of AF tissues in the future. Acknowledgment This project is supported by 973 The National Basic Research Program of China (973 Program), Hong Kong University Grants Committee-TRS Theme-based Research Scheme, and AOSpine.

Scaffolds from biomaterials: advantages and limitations in bone and tissue engineering

AbstractNowadays, there has been immense progress in developing materials to support transplanted cells. Nevertheless, the complexity of tissues is far beyond what is found in the most advanced scaffolds. This article reviews the types of biomaterials and their resulting scaffolds in the bio-engineering of bone and tissues by presenting an overview of the characteristics of ideal scaffold in tissue engineering along with types of scaffolds and examples of previous studies where these scaffolds have been applied. The advantages of scaffolds, and the three-dimensional culture system and its used commercially available scaffold is presented. Challenges encountered in the application of these scaffolds in bone and tissue engineering is also highlighted. Used method was by acquisition of materials through Google scholar, Science direct, PubMed and University library archives. Proper knowledge of the above highlighted facts will go a long way in re-addressing the production of scaffolds for bone and tissue engineering. With the proliferation of innovative applications in bioactive glasses and glass ceramics, the greater need for specific understanding of cell biology with emphasis on cellular differentiation, cell to cell interaction and extracellular matrix formation in engineering of bone and tissues becomes inevitable. This will enhance scaffold production, bone regeneration and transplantation outcome.

3D Printing of Customized Implants for Treatment of Orofacial Deformities and Defects

Acute or refractory orofacial deformities and defects present surgeons with numerous reconstructive challenges.Such defects are currently reconstructed using microvascular free flaps, non‐vascular autogenous bone and/or skin grafts, or reconstruction with xenografts or synthetic materials. Using these methods, surgeons are constrained by the size and complexity of the defect; defects larger than 5 cm are difficult to reconstruct with these techniques, so are those defects that involve the anterior mandibular region. Lack of predictability of graft success, as well as the lack of predictability of the esthetic and functional outcome of a non‐vascular grafting makes it necessary to use a vascularized free flap in many of these cases. Such procedures are lengthy and challenging despite the improvements in the technology and the techniques. Patients experience long recovery periods and are exposed to related perioperative morbidities that increase health care costs, increase time lost from work, and negatively affect the patients’ quality of life.3D printing is currently being intensely studied by a diverse set of applications, including the development of bioengineered tissues, as well as the production of functional biomedical materials and devices for dental and orthopedic applications. Producing vascularized 3D‐printed customized implants/scaffolds that are infused with stem cells, and designed to replace many of the traditional surgical procedures can be considered as a new method to treat orofacial deformities and defects. These implants/scaffolds will be tailored to meet the patient's current condition, age, and prior medical history and designed for tension free soft tissue closure, enhanced vascularity and tissue formation, and the prevention of micromobilityWe anticipate that this method will significantly improve the quality of the life of patients affected by numerous oral and craniofacial pathologic conditions.