Current reconstructive techniques for continuity defects of the mandible include the use of free flaps, bone grafts, and alloplastic materials. New methods of regenerative medicine designed to restore tissues depend mainly on the so-called extrinsic neovascularization, where the neovascular bed originates from the periphery of the construct. This method is not applicable for large defects in irradiated fields.
We are introducing a new animal model for mandibular reconstruction using intrinsic axial vascularization by the Arterio-Venous (AV) loop. In order to test this model, we made cadaveric, mechanical loading, and surgical pilot studies on adult male goats. The cadaveric study aimed at defining the best vascular axis to be used in creating the AV loop in the mandibular region. Mechanical loading studies (3 points bending test) were done to ensure that the mechanical properties of the mandible were significantly affected by the designed defect, and to put a base line for further mechanical testing after bone regeneration. A pilot surgical study was done to ensure smooth operative and post operative procedures.
The best vascular axis to reconstruct defects in the posterior half of the mandible is the facial artery (average length 32.5 ± 1.9 mm, caliber 2.5 mm), and facial vein (average length 33.3 ± 1.8 mm, caliber 2.6 mm). Defects in the anterior half require an additional venous graft. The defect was shown to be significantly affecting the mechanical properties of the mandible (P value 0.0204). The animal was able to feed on soft diet from the 3rd postoperative day and returned to normal diet within a week. The mandible did not break during the period of follow up (2 months).
Our model introduces the concept of axial vascularization of mandibular constructs. This model can be used to assess bone regeneration for large bony defects in irradiated fields. This is the first study to introduce the concept of axial vascularization using the AV loop for angiogenesis in the mandibular region. Moreover, this is the first study aiming at axial vascularization of synthetic tissue engineering constructs at the site of the defect without any need for tissue transfer (in contrast to what was done previously in prefabricated flaps).
The current management of large mandibular resection defects involves harvesting of autogenous bone grafts and repeated bending of generic reconstruction plates. However, the major disadvantage of harvesting large autogenous bone grafts is donor site morbidity and the major drawback of repeated reconstruction plate bending is plate fracture and difficulty in reproducing complex facial contours. The aim of this study was to describe reconstruction of three mandibular ameloblastoma resection defects using tissue engineered constructs of beta-tricalcium phosphate (β-TCP) granules, recombinant human bone morphogenetic protein-2 (rhBMP-2), and Good Manufacturing Practice (GMP) level autologous adipose stem cells (ASCs) with progressively increasing usage of computer-aided manufacturing (CAM) technology.
Materials and Methods:
Patients’ three-dimensional (3D) images were used in three consecutive patients to plan and reverse-engineer patient-specific saw guides and reconstruction plates using computer-aided additive manufacturing. Adipose tissue was harvested from the anterior abdominal walls of three patients before resection. ASCs were expanded ex vivo over 3 weeks and seeded onto a β-TCP scaffold with rhBMP-2. Constructs were implanted into patient resection defects together with rapid prototyped reconstruction plates.
All three cases used one step in situ bone formation without the need for an ectopic bone formation step or vascularized flaps. In two of the three patients, dental implants were placed 10 and 14 months following reconstruction, allowing harvesting of bone cores from the regenerated mandibular defects. Histological examination and in vitro analysis of cell viability and cell surface markers were performed and prosthodontic rehabilitation was completed.
Constructs with ASCs, β-TCP scaffolds, and rhBMP-2 can be used to reconstruct a variety of large mandibular defects, together with rapid prototyped reconstruction hardware which supports placement of dental implants.
Adipose-derived stem cells; beta-tricalcium phosphate; bone morphogenetic protein; computer-aided design
Co-axial electrospun fibers can offer both topographical and biochemical cues for tissue engineering applications. In this study, we demonstrate the sustained treatment of hemophilia through a non-viral, tissue engineering approach facilitated by growth factor-releasing co-axial electrospun fibers. FVIII-producing skeletal myotubes were first engineered on aligned electrospun fibers in vitro, followed by implantation in hemophilic mice with or without a layer of core-shell electrospun fibers designed to provide sustained delivery of angiogenic or lymphangiogenic growth factors, which serves to stimulate the lymphatic or vascular systems to enhance the FVIII transport from the implant site into systemic circulation. Upon subcutaneous implantation into hemophilic mice, the construct seamlessly integrated with the host tissue within one month, and specifically induced either vascular or lymphatic network infiltration in accordance with the growth factors released from the electrospun fibers. Engineered constructs that induced angiogenesis resulted in sustained elevation of plasma FVIII and significantly reduced blood coagulation time for at least two months. Biomaterials-assisted functional tissue engineering was shown in this study to offer protein replacement therapy for a genetic disorder such as hemophilia.
Hemophilia; skeletal muscle engineering; angiogenesis; lymphangiogenesis; electrospinning; protein replacement therapy
In the last two decades, regenerative medicine has shown the potential for “bench-to-bedside” translational research in specific clinical settings. Progress made in cell and stem cell biology, material sciences and tissue engineering enabled researchers to develop cutting-edge technology which has lead to the creation of nonmodular tissue constructs such as skin, bladders, vessels and upper airways. In all cases, autologous cells were seeded on either artificial or natural supporting scaffolds. However, such constructs were implanted without the reconstruction of the vascular supply, and the nutrients and oxygen were supplied by diffusion from adjacent tissues. Engineering of modular organs (namely, organs organized in functioning units referred to as modules and requiring the reconstruction of the vascular supply) is more complex and challenging. Models of functioning hearts and livers have been engineered using “natural tissue” scaffolds and efforts are underway to produce kidneys, pancreata and small intestine. Creation of custom-made bioengineered organs, where the cellular component is exquisitely autologous and have an internal vascular network, will theoretically overcome the two major hurdles in transplantation, namely the shortage of organs and the toxicity deriving from lifelong immuno-suppression. This review describes recent advances in the engineering of several key tissues and organs.
decellularization; extracellular matrix; regenerative medicine; scaffold; solid organ transplantation; stem cells; tissue engineering
It is becoming evident that tissue-engineered constructs adapt to altered mechanical loading, and that specific combinations of multidirectional loads appear to have a synergistic effect on the remodeling. However, most studies of mechanical stimulation of engineered vascular tissue engineering employ only uniaxial stimulation. Here we present a novel computer-controlled bioreactor and biomechanical testing device designed to precisely and simultaneously control mean and cyclic values of transmural pressure (at rates up to 1 Hz and ranges of 40 mmHg), luminal flow rate, and axial length (or load) applied to gel-derived, scaffold-derived, and self-assembly-derived tissue-engineered blood vessels during culture, while monitoring vessel geometry with a resolution of 6.6 μm. Intermittent monitoring of the extracellular matrix and cells is accomplished on live tissues using multi-photon confocal microscopy under unloaded and loaded conditions at multiple time-points in culture (on the same vessel) to quantify changes in cell and extracellular matrix content and organization. This same device is capable of performing intermittent cylindrical biaxial biomechanical testing at multiple time-points in culture (on the same vessel) to quantify changes in the mechanical behavior during culture. Here we demonstrate the capabilities of this new device on self-assembly-derived and collagen-gel-derived tissue-engineered blood vessels.
The objective of this study was to evaluate 2 years post-surgical loss of three-dimensional correction in adolescent idiopathic scoliosis (AIS) patients using multi-planar reconstruction computed tomography (CT).
Twenty-seven AIS patients treated by segmental pedicle screw (PS) constructs were included in this study. Correction in the axial plane was evaluated using the “relative apical vertebral rotation angle” (rAVR), defined as the difference between the axial rotation angles of the upper instrumented vertebra and the apical vertebra on reconstructed axial CT images. The Cobb angle of the main curve and apical vertebral translation was measured to evaluate the coronal correction. Thoracic kyphosis was also measured for the evaluation of sagittal profile. Measurements were performed before surgery, and 1 week and 2 years after surgery. The relationships between the correction losses and skeletal maturity, and variety of spinal constructs were also evaluated.
The mean preoperative Cobb angle of the major curve was 59.1° ± 11.2° before and 13.0° ± 7.2° immediately after surgery. Two years later, the mean Cobb angle had increased significantly, to 15.5° ± 7.8°, with a mean correction loss of 2.5° ± 1.5° (p < 0.001). The mean preoperative rAVR of 28.5° ± 8.4° was corrected to 15.8° ± 7.8° after surgery. It had increased significantly to 18.5 ± 8.4 by 2 years after surgery, with a mean correction loss of 2.7° ± 1.0° (p < 0.001). The mean correction losses for both the Cobb angle and rAVR were significantly greater in the skeletally immature patients. The significant correlations were recognized between the correction losses and the proportion of multi-axial screws, and the materials of constructs.
Statistically significant loss of correction in the Cobb angle and apical vertebral axial rotation angle (AVR) were recognized 2 years after surgery using PS constructs. The correction losses, especially AVR, were more evident in the skeletally immature patients, and in patients treated with more multi-axial screws and with titanium constructs rather than with stainless constructs.
Adolescent idiopathic scoliosis; Apical vertebral rotation; Correction loss; Coronal correction
The skin paddle of the free fibula flap receives its vascular supply from septocutaneous perforators, musculocutaneous perforators or from both, and these perforators might originate from the peroneal or posterior tibial vessels or from both. The objective of this study was to classify the skin paddles based on the dominance of vascular contribution by these axial vessels through their different perforator systems.
Materials and Methods:
A retrospective analysis of 5-year data of 386 free fibula flaps used in oro-mandibular reconstruction was done and the skin paddle vascularity was studied. While majority of the skin paddles received their blood supply from the peroneal septocutaneous perforators, a few had their dominant supply from the soleus musculocutaneous perforators in addition to peroneal septocutaneous perforators. In few cases, the soleus musculocutaneous perforators were the sole source of blood supply to the skin paddle. The limitation in this study was the inability to augment the clinical observation with cadaveric study.
The skin paddle of the free fibula flap was classified into four different types (a–d) based on the dominance of vascular contribution by axial vessels of the leg.
The skin paddle of the free fibula flap has reliable blood supply, but a thorough knowledge of the variations in vascular pattern of the skin paddle is required especially to salvage the larger paddles used in the reconstruction complex oro-mandibular defects.
Free fibula flap; musculocutaneous perforators; septo cutaneous perforators; skin paddle; vascular supply
The goals of treatment for hemifacial microsomia include horizontalization of occlusal plane and acquisition of facial symmetry. Although horizontalization of occlusal plane can be easily achieved, facial symmetry, particularly in relation to mandibular contour, can be difficult to attain. Soft tissue is generally reconstructed to correct facial asymmetry, and no studies have described correction of facial asymmetry through skeletal reconstruction.
A 12-year-old girl presented with grade IIb right-sided hemifacial microsomia. She was treated using Nakajima's angle-variable internal distraction (NAVID) system for mandibular body distraction.
Following treatment, appropriate facial symmetry was achieved, and the patient was extremely satisfied with the results.
Thus, we successfully treated the present patient by our novel method involving distraction osteogenesis. This method was effective and useful for several reasons including; the changes were not accompanied by postoperative tissue absorption, donor sites were not involved, and the treatment outcome could be reevaluated by adjusting distraction while the patient's appearance was being remodeled.
Distraction osteogenesis; hemifacial microsomia; mandibular body distraction; mentular distraction
Systemic sclerosis (SSc) is a multisystem connective tissue disease of unknown etiology. The hallmark of SSc is scleroderma, referring to the presence of thickened, hardened skin. Oral and maxillofacial manifestations of the disease are numerous including masklike appearance, trismus, muscular atrophy, thin atrophied lips, secondary microstomia, xerostomia, rigidity of tongue and lips, widening of the periodontal ligament space, trigeminal neuralgia, and resorption of the mandible. A 35-year-old woman with limited cutaneous SSc presented with bilateral mandibular condylysis, severe class II mandibular deficiency, and large anterior open bite and limited range of mandibular opening at 27 mm. Surgical correction consisted of bilateral total temporomandibular joint reconstruction with stock prostheses combined with Le Fort I maxillary impaction and functional advancement genioplasty. This resulted in a functional occlusion with elimination of her open bite and a more esthetic profile. Her occlusion has remained stable at 7 months. The incidence of mandibular resorption in SSc has been found to be 20% to 33%. The mandibular angles are most commonly involved (37.6%), followed by the condyle (20.8%), coronoid process (20.0%), and the posterior border of the ascending ramus (14.4%). Bilateral condylysis is present in 13.7% of the cases. Very few cases of surgical correction of malocclusion induced by SSc-related condylysis have been reported in the literature. To the best of our knowledge, this is the first case report of bilateral condylysis from SSc where surgical replacement of the resorbed condyles was attempted. Bilateral total temporomandibular joint replacement can give these patients a functional occlusion, improved facial balance, and improved quality of life.
Scleroderma; systemic; temporomandibular joint; arthroplasty; replacement; osteolysis
Tissue engineering has become a new approach for repairing bony defects. Highly porous osteoconductive scaffolds perform the important role for the success of bone regeneration. By biomimetic strategy, apatite-coated porous biomaterial based on silk fibroin scaffolds (SS) might provide an enhanced osteogenic environment for bone-related outcomes. To assess the effects of apatite-coated silk fibroin (mSS) biomaterials for bone healing as a tissue engineered bony scaffold, we explored a tissue engineered bony graft using mSS seeded with osteogenically induced autologous bone marrow stromal cells (bMSCs) to repair inferior mandibular border defects in a canine model. The results were compared with those treated with bMSCs/SS constructs, mSS alone, SS alone, autologous mandibular grafts and untreated blank defects. According to radiographic and histological examination, new bone formation was observed from 4 weeks post-operation, and the defect site was completely repaired after 12 months for the bMSCs/mSS group. In the bMSCs/SS group, new bone formation was observed with more residual silk scaffold remaining at the center of the defect compared with the bMSCs/mSS group. The engineered bone with bMSCs/mSS achieved satisfactory bone mineral densities (BMD) at 12 months post-operation close to those of normal mandible (p>0.05). The quantities of newly formed bone area for the bMSCs/mSS group was higher than the bMSCs/SS group (p<0.01), but no significant differences were found when compared with the autograft group (p>0.05). In contrast, bony defects remained in the center with undegraded silk fibroin scaffold and fibrous connective tissue, and new bone only formed at the periphery in the groups treated with mSS or SS alone. The results suggested apatite-coated silk fibroin scaffolds combined with bMSCs could be successfully used to repair mandibular critical size border defects and the premineralization of these porous silk fibroin protein scaffolds provided an increased osteoconductive environment for bMSCs to regenerate sufficient new bone tissue.
Tissue engineering; Silk; Apatite; Bone marrow stromal cells; Canine
The reconstruction of an auricle for congenital deformity or following trauma remains one of the greatest challenges in reconstructive surgery. Tissue-engineered (TE) three-dimensional (3D) cartilage constructs have proven to be a promising option, but problems remain with regard to cell vitality in large cell constructs. The supply of nutrients and oxygen is limited because cultured cartilage is not vascular integrated due to missing perichondrium. The consequence is necrosis and thus a loss of form stability. The micro-surgical implantation of an arteriovenous loop represents a reliable technology for neovascularization, and thus vascular integration, of three-dimensional (3D) cultivated cell constructs. Auricular cartilage biopsies were obtained from 15 rabbits and seeded in 3D scaffolds made from polycaprolactone-based polyurethane in the shape and size of a human auricle. These cartilage cell constructs were implanted subcutaneously into a skin flap (15×8 cm) and neovascularized by means of vascular loops implanted micro-surgically. They were then totally enhanced as 3D tissue and freely re-implanted in-situ through microsurgery. Neovascularization in the prefabricated flap and cultured cartilage construct was analyzed by microangiography. After explantation, the specimens were examined by histological and immunohistochemical methods. Cultivated 3D cartilage cell constructs with implanted vascular pedicle promoted the formation of engineered cartilaginous tissue within the scaffold in vivo. The auricles contained cartilage-specific extracellular matrix (ECM) components, such as GAGs and collagen even in the center oft the constructs. In contrast, in cultivated 3D cartilage cell constructs without vascular pedicle, ECM distribution was only detectable on the surface compared to constructs with vascular pedicle. We demonstrated, that the 3D flaps could be freely transplanted. On a microangiographic level it was evident that all the skin flaps and the implanted cultivated constructs were well neovascularized. The presented method is suggested as a promising alternative towards clinical application of engineered cartilaginous tissue for plastic and reconstructive surgery.
Background and objective: Mandibular reconstruction following tumor ablative surgery had been a challenge. It has gone through days of temporary stabilization with k-wire, stainless steel reconstruction plate to avascularized and vascularized bone grafts with varying degree of success and failure. Reconstruction with vascularized bone grafts, though most definitive, requires special expertise, expensive equipment, and long operative time. It also produces donor site morbidity and requires a significant learning curve. With the development of transport distraction techniques there has been a paradigm shift from “reconstructive” to “regenerative” surgery. The objective of this study was to identify the feasibility of an internal device for reconstruction of extensive mandibular defects. Methods and material: This article is to highlight a process of attempted mandibular regeneration in two cases using an indigenously designed distractor device. In individuals with extensive post ablative mandibular defects who were unwilling to have a secondary surgical site or were medically unfit for a long reconstructive procedure, the distraction technique can be used to reconstruct the lost mandibular structures. Conclusion: A satisfactory amount of regenerate was achieved using a bifocal distraction osteogenesis technique for extensive defects of the mandible. The custom made device which was used for this purpose was moderately satisfactory and requires further evaluation and refinement.
Transport distraction; extensive mandibular defects; single unit distractor device; mandibular reconstruction
The anterior cruciate ligament (ACL) is the most commonly injured intra-articular ligament of the knee. The insufficient vascularization of this tissue prevents it from healing completely after extreme tearing or rupture, creating a need for ACL grafts for reconstruction. The limitations of existing grafts have motivated the investigation of tissue engineered ACL grafts. A successful tissue engineered graft must possess mechanical properties similar to the ACL; to date no commercially available synthetic graft has achieved this. To accomplish this goal we have combined the techniques of polymer fiber braiding and twisting to design a novel poly L-lactic acid (PLLA) braid-twist scaffold for ACL tissue engineering. The scaffold is designed to accurately mimic the biomechanical profile and mechanical properties of the ACL. In this study, braid-twist scaffolds were constructed and compared to braided scaffolds and twisted fiber scaffolds.
The addition of fiber twisting to the braided scaffold resulted in a significant increase in the ultimate tensile strength, an increase in ultimate strain, and an increase in the length of the toe region in these constructs over scaffolds that were braided. Based on the findings of this study, the braid-twist scaffold studied was found to be a promising construct for tissue engineering of the anterior cruciate ligament.
anterior cruciate ligament (ACL); poly (L-lactic acid) (PLLA); scaffold; polymer; tissue engineering
Free fibula flap is the most common free tissue transfer for maxillary and mandibular reconstructions. The distal part of the harvested bone is transferred, while the proximal part is removed by sub-periosteum dissection. The vascularized periosteum attached to the vascular pedicle has osteogenic potential. 61 patients reconstructed with free fibula flaps were divided in 2 groups: 41 flaps performed with a standard technique and 20 flaps performed by dissecting the periosteum from the pedicle. Patients were followed up with orthopantomography and CT scan at 6, 12, 18 and 24 months after surgery. The minimum follow-up time was 18 months. With retrospective analysis of the first group we diagnosed 7 pedicle ossifications on 41 reconstructions (17%). In the second group, no pedicle ossification was observed (p < 0.05). The dissection of periosteum from the vascular pedicle of free fibula flaps avoids the risk of ossification.
Free fibula flap; Vascular pedicle ossification; Mandibular reconstruction; Maxillary reconstruction; Microsurgery
Over the years, cardiovascular diseases continue to increase and affect not only human health but also the economic stability worldwide. The advancement in tissue engineering is contributing a lot in dealing with this immediate need of alleviating human health. Blood vessel diseases are considered as major cardiovascular health problems. Although blood vessel transplantation is the most convenient treatment, it has been delimited due to scarcity of donors and the patient's conditions. However, tissue-engineered blood vessels are promising alternatives as mode of treatment for blood vessel defects. The purpose of this paper is to show the importance of the advancement on biofabrication technology for treatment of soft tissue defects particularly for vascular tissues. This will also provide an overview and update on the current status of tissue reconstruction especially from autologous stem cells, scaffolds, and scaffold-free cellular transplantable constructs. The discussion of this paper will be focused on the historical view of cardiovascular tissue engineering and stem cell biology. The representative studies featured in this paper are limited within the last decade in order to trace the trend and evolution of techniques for blood vessel tissue engineering.
Mandibular defect occurs more frequently in recent years, and clinical repair operations via bone transplantation are difficult to be further improved due to some intrinsic flaws. Tissue engineering, which is a hot research field of biomedical engineering, provides a new direction for mandibular defect repair. As the basis and key part of tissue engineering, scaffolds have been widely and deeply studied in regards to the basic theory, as well as the principle of biomaterial, structure, design, and fabrication method. However, little research is targeted at tissue regeneration for clinic repair operations. Since mandibular bone has a special structure, rather than uniform and regular structure in existing studies, a methodology based on tissue engineering is proposed for mandibular defect repair in this paper. Key steps regarding scaffold digital design, such as external shape design and internal microstructure design directly based on triangular meshes are discussed in detail. By analyzing the theoretical model and the measured data from the test parts fabricated by rapid prototyping, the feasibility and effectiveness of the proposed methodology are properly verified. More works about mechanical and biological improvements need to be done to promote its clinical application in future.
Digital design; Mandibular defect; Scaffold; Tissue engineering
Current limitations of exogenous scaffolds or extracellular matrix based materials have underlined the need for alternative tissue-engineering solutions. Scaffolds may elicit adverse host responses and interfere with direct cell-cell interaction, as well as assembly and alignment of cell-produced ECM. Thus, fabrication techniques for production of scaffold-free engineered tissue constructs have recently emerged. Here we report on a fully biological self-assembly approach, which we implement through a rapid prototyping bioprinting method for scaffold-free small diameter vascular reconstruction. Various vascular cell types, including smooth muscle cells and fibroblasts, were aggregated into discrete units, either multicellular spheroids or cylinders of controllable diameter (300 to 500 μm). These were printed layer-by-layer concomitantly with agarose rods, used here as a molding template. The post-printing fusion of the discrete units resulted in single- and double-layered small diameter vascular tubes (OD ranging from 0.9 to 2.5 mm). A unique aspect of the method is the ability to engineer vessels of distinct shapes and hierarchical trees that combine tubes of distinct diameters. The technique is quick and easily scalable.
Tissue engineering solutions focused on the temporomandibular joint (TMJ) have expanded in number and variety over the past decade to address the treatment of TMJ disorders. The existing literature on approaches for healing small defects in the TMJ condylar cartilage and subchondral bone, however, is sparse. The purpose of this study was thus to evaluate the performance of a novel gradient-based scaffolding approach to regenerate osteochondral defects in the rabbit mandibular condyle.
MATERIALS AND METHODS
Miniature bioactive plugs for regeneration of small mandibular condylar defects in New Zealand White rabbits were fabricated. The plugs were constructed from poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres with a gradient transition between cartilage-promoting and bone-promoting growth factors.
At six weeks of healing, results suggested that the implants provided support for the neo-synthesized tissue as evidenced by histology and 9.4T magnetic resonance imaging.
The inclusion of bioactive factors in a gradient-based scaffolding design is a promising new treatment strategy for focal defect repair in the TMJ.
TMJ; Osteochondral; Interface; Gradient; Microsphere; PLGA; BMP-2; TGF-β1
The purpose of ultrasound elastography is to identify lesions by reconstructing the hardness characteristics of tissue reconstructed from ultrasound data. Conventional quasi-static ultrasound elastography is easily applied to obtain axial strain components along the compression direction, with the results inverted to represent the distribution of tissue hardness under the assumption of constant internal stresses. However, previous works of quasi-static ultrasound elastography have found it difficult to obtain the lateral and shear strain components, due to the poor lateral resolution of conventional ultrasound probes. The physical nature of the strain field is a continuous vector field, which should be fully described by the axial, lateral, and shear strain components, and the clinical value of lateral and shear strain components of deformed tissue is gradually being recognized by both engineers and clinicians. Therefore, a biomechanical-model-constrained filtering framework is proposed here for recovering a full displacement field at a high spatial resolution from the noisy ultrasound data. In our implementation, after the biomechanical model constraint is integrated into the state-space equation, both the axial and lateral displacement components can be recovered at a high spatial resolution from the noisy displacement measurements using a robust filter, which only requires knowledge of the worst-case noise levels in the measurements. All of the strain components can then be calculated by applying a gradient operator to the recovered displacement field. Numerical experiments on synthetic data demonstrated the robustness and effectiveness of our approach, and experiments on phantom data and in-vivo clinical data also produced satisfying results.
Significant advances have been made in bone tissue engineering (TE) in the past decade. However, classical bone TE strategies have been hampered mainly due to the lack of vascularization within the engineered bone constructs, resulting in poor implant survival and integration. In an effort toward clinical success of engineered constructs, new TE concepts have arisen to develop bone substitutes that potentially mimic native bone tissue structure and function. Large tissue replacements have failed in the past due to the slow penetration of the host vasculature, leading to necrosis at the central region of the engineered tissues. For this reason, multiple microscale strategies have been developed to induce and incorporate vascular networks within engineered bone constructs before implantation in order to achieve successful integration with the host tissue. Previous attempts to engineer vascularized bone tissue only focused on the effect of a single component among the three main components of TE (scaffold, cells, or signaling cues) and have only achieved limited success. However, with efforts to improve the engineered bone tissue substitutes, bone TE approaches have become more complex by combining multiple strategies simultaneously. The driving force behind combining various TE strategies is to produce bone replacements that more closely recapitulate human physiology. Here, we review and discuss the limitations of current bone TE approaches and possible strategies to improve vascularization in bone tissue substitutes.
This case report describes a 35-year-old Caucasian radiographer who presented with a significant mandibular bony defect following multiple excisions of an ameloblastoma. As a result, there was an absence of teeth on the lower-right mandible and a clear defect in the mandible. The treatment objectives were to rebuild the mandibular defect, with a long-term view of inserting dental implants. In a novel approach outlined in this presentation, tissue expansion of the submucosa, a titanium construct and an iliac bone graft were used to rebuild the patient’s jaw. This surgical technique is recommended for the reconstruction of bony defects.
Premineralized silk fibroin protein scaffolds (mSS) were prepared to combine the osteoconductive properties of biological apatite with aqueous-derived silk scaffold (SS) as a composite scaffold for bone regeneration. The aim of present study was to evaluate the effect of premineralized silk scaffolds combined with bone morphogenetic protein-2 (BMP-2) modified bone marrow stromal cells (bMSCs) to repair mandibular bony defects in a rat model. bMSCs were expanded and transduced with adenovirus AdBMP-2, AdLacZ gene in vitro. These genetically modified bMSCs were then combined with premineralized silk scaffolds to form tissue engineered bone. Mandibular repairs with AdBMP-2 transduced bMSCs/mSS constructs were compared with those treated with AdLacZ transduced bMSCs/mSS constructs, native (nontransduced) bMSCs/mSS constructs and mSS alone. Eight weeks post-operation, the mandibles were explanted and evaluated by radiographic observation, micro-CT, histological analysis and immunohistochemistry. The presence of BMP-2 gene enhanced tissue engineered bone in terms of the most new bone formed and the highest local bone mineral densities (BMD) found. These results demonstrated that premineralized silk scaffold could serve as a potential substrate for bMSCs to construct tissue engineered bone for mandibular bony defects. BMP-2 gene therapy and tissue engineering techniques could be used in mandibular repair and bone regeneration.
Mandibular first molar is the most important tooth with complicated morphology. In finite element (FE) studies, investigators usually prefer to model anterior teeth with a simple and single straight root; it makes the results deviate from the actual case. The most complicated and time-consuming step in FE studies is modeling of the desired tooth, thus this study was performed to establish a finite element method (FEM) of reconstructing a mandibular first molar with the greatest precision.
Materials and Methods
An extracted mandibular first molar was digitized, and then radiographed from different aspects to achieve its outer and inner morphology. The solid model of tooth and root canals were constructed according to this data as well as the anatomy of mandibular first molar described in the literature.
A three-dimensional model of mandibular first molar was created, giving special consideration to shape and root canal system dimensions.
This model may constitute a basis for investigating the effect of different clinical situations on mandibular first molars in vitro, especially on its root canal system. The method described here seems feasible and reasonably precise foundation for investigations.
Finite Element Method; Mandibular First Molar; Three-dimensional Modeling
The anterior cruciate ligament (ACL), a major stabilizer of the knee, is commonly injured. Because of its intrinsic poor healing ability, a torn ACL is usually reconstructed by a graft. We developed a multi-phasic, or bone–ligament–bone, tissue-engineered construct for ACL grafts using bone marrow stromal cells and sheep as a model system. After 6 months in vivo, the constructs increased in cross section and exhibited a well-organized microstructure, native bone integration, a functional enthesis, vascularization, innervation, increased collagen content, and structural alignment. The constructs increased in stiffness to 52% of the tangent modulus and 95% of the geometric stiffness of native ACL. The viscoelastic response of the explants was virtually indistinguishable from that of adult ACL. These results suggest that our constructs after implantation can obtain physiologically relevant structural and functional characteristics comparable to those of adult ACL. They present a viable option for ACL replacement.
Initially hailed as the ultimate solution to organ failure, engineering of vascularized tissues such as the liver has stalled because of the need for a well-structured circulatory system that can maintain the cells seeded inside the construct. A new approach has evolved to overcome this obstacle. Whole-organ decellularization is a method that retains most of the native vascular structures of the organ, providing microcirculatory support and structure, which can be anastomosed with the recipient circulation. The technique was first applied to the heart and then adapted for the liver. Several studies have shown that cells can be eliminated, the extracellular matrix and vasculature are reasonably preserved and, after repopulation with hepatocytes, these grafts can perform hepatic functions in vitro and in vivo. Progress is rapidly being made as researchers are addressing several key challenges to whole-organ tissue engineering, such as ensuring correct cell distribution, nonparenchymal cell seeding, blood compatibility, immunological concerns, and the source of cells and matrices.