Cell-based tissue engineering for lung regeneration

2007 ◽  
Vol 292 (2) ◽  
pp. L510-L518 ◽  
Author(s):  
Cristiano F. Andrade ◽  
Amy P. Wong ◽  
Thomas K. Waddell ◽  
Shaf Keshavjee ◽  
Mingyao Liu

Emphysema is a chronic lung disease characterized by alveolar enlargement and tissue loss. Tissue engineering represents an attractive potential for regeneration of several organ systems. The complex three-dimensional architectural structure of lung parenchyma requiring connections of alveolar units to airways and the pulmonary circulation makes this strategy less optimistic. In the present study, we used Gelfoam sponge as a scaffold material, supplemented with fetal rat lung cells as progenitors, to explore the potential application of cell-based tissue engineering for lung regeneration in adult rats. After injection into lung parenchyma, the sponge showed porous structures similar to alveolar units. It did not induce severe local inflammatory response. Fetal lung cells in the sponge were able to survive in the adult lung for at least 35 days, determined by CMTMR [5-(and-6)-{[(4-chloromethyl)benzoyl]amino}tetramethylrhodamine] labeling. Proliferation of cells within the sponge was demonstrated in vivo by bromodeoxyuridine (BrdU) labeling. Cells formed “alveolar-like structures” at the border between the sponge and the surrounding lung tissue with positive immunohistochemical staining for epithelial and endothelial cells. Neovascularization of the sponge was demonstrated with India ink perfusion. The sponge degraded after several months. This study suggests that cell-based tissue engineering possesses the potential to regenerate alveolar-like structures, an important step towards our ultimate goal of lung regeneration.

2014 ◽  
Vol 1687 ◽  
Author(s):  
Roshan James ◽  
Cato T. Laurencin

ABSTRACTCurrent treatment options for tissue loss or organ failure include organ/tissue transplantation of autografts/allografts, delivery of bioactive agents, and utilization of synthetic replacements composed of metals, polymers, and ceramics. However each strategy suffers from a number of limitations. The early attempts to overcome these drawbacks led to the emergence of tissue engineering that provided viable tissue substitutes using a combination of biomaterials, cells, and factors. This approach was ideally suited to repair damaged tissues; however the substitution and regeneration of large tissue volumes and multi-level tissues such as complex organ systems require more than optimal combinations of biomaterials and biologics.‘Regenerative Engineering’ is aimed at creating large and complex tissue systems incorporating advances in material science, stem cell technology and developmental biology. We believe that recent breakthrough technologies in advanced materials science and nanotechnology allow us to recapitulate native tissues. The novel designer polymers incorporate bioactivity and physical features specific to a regeneration application. Overall, engineered materials and scaffolds afford selective control of cell sensitivity, and precise control of temporal and spatial stimulatory cues. We aim to build multi-level systems such as organs through location-specific topographies and physico-chemical cues incorporated into a continuous phase using a combination of classical top-down tissue engineering approach with bottom-up strategies used in regenerative biology.Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration show extremely limited endogenous regenerative capacity. The development of material and structural platforms to modulate stem cell behavior to enhance regeneration is an area of great interest. In this manuscript we cover some examples of material development, and incorporation of topographical and cytokine cues to modulate the differentiation of hard and soft musculoskeletal tissues such as bone, ligament and tendon.


2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S82-S83
Author(s):  
Zachary J Collier ◽  
Katherine J Choi ◽  
Ian F Hulsebos ◽  
Christopher H Pham ◽  
Haig A Yenikomshian ◽  
...  

Abstract Introduction Blast injuries present unique challenges to civilian and military healthcare providers because of the complex and often severe nature of injuries spanning numerous anatomical regions, tissue types, and organ systems. Due to these factors, we devised a novel wound-focused classification system for implementation during triage and management of blast injuries to optimize outcomes and applied this system to patients treated at an ABA-certified burn center over 5 years. Methods A retrospective analysis of patients treated by an ABA-certified burn center for blast-related injuries from September 1, 2014 to October 31, 2019 was performed. Demographics, mechanism and distribution of injuries, interventions, and outcomes were evaluated. Injuries were classified using a wound-focused classification comprised of four zones: 1) areas closest to blast epicenter that had total or near-total tissue loss from the blast; 2) adjacent areas with thermal and chemical burns; 3) distant sites with shrapnel-related wounds; 4) injuries arising from barotrauma. Results We identified 64 patients who were mostly male (84%), averaging 38 ± 14 years old. Injury mechanisms included fireworks (19%), industrial accidents (16%), volatile fuels and drug labs (45%), and others including can, battery, lighter explosions (20%). All mechanisms had equivalent frequency of Zone 2 injuries with an average TBSA of 17 ± 18%. Drug-related blasts caused the highest TBSA (34 ± 23%) and the most full-thickness burns (33% vs average 23%). Fireworks had over five times (17% vs. 3%) more Zone 3 and three times (25% vs 8%) more Zone 4 injuries compared to the other mechanisms. Upper extremities were involved at twice the rate of other body regions (43% vs 19%). Patients presenting to our burn team over 24 hours after initial injury had infections in 50% of cases – a four-fold increase compared to non-delayed presentations (50% vs 13%). Overall, 45% required surgery (32% grafting, 3% flaps) but 100% of the drug-related blasts needed surgical intervention. Some patients (58%) required ICU admission with the highest rate (83%) in the drug-related group. Conclusions Blast injuries most often required admission for management of the Zone 2 component. Each blast mechanism resulted in distinct distributions of injury although fireworks had the greatest number of Zone 1, 3, and 4 injuries. Firework blasts were often less severe and more likely to present delayed with infectious complications. Larger blast mechanisms including drug-related lab explosions as well as industrial blasts had the highest rates of ICU admission, TBSA, full thickness depth, upper extremity involvement, and need for surgical intervention.


2018 ◽  
Vol 9 ◽  
pp. 204173141877294 ◽  
Author(s):  
Pavan Kottamasu ◽  
Ira Herman

Donor organ shortage remains a clear problem for many end-stage organ patients around the world. The number of available donor organs pales in comparison with the number of patients in need of these organs. The field of tissue engineering proposes a plausible solution. Using stem cells, a patient’s autologous cells, or allografted cells to seed-engineered scaffolds, tissue-engineered constructs can effectively supplement the donor pool and bypass other problems that arise when using donor organs, such as who receives the organ first and whether donor organ rejection may occur. However, current research methods and technologies have been unable to successfully engineer and vascularize large volume tissue constructs. This review examines the current perfusion methods for ex vivo organ systems, defines the different types of vascularization in organs, explores various strategies to vascularize ex vivo organ systems, and discusses challenges and opportunities for the field of tissue engineering.


MRS Bulletin ◽  
1996 ◽  
Vol 21 (11) ◽  
pp. 52-54 ◽  
Author(s):  
Prabhas V. Moghe

Tissue engineering involves the application of physical and life sciences to develop functional substitutes for dysfunctional organs or tissue structures. From an engineering standpoint, tissues contain two basic components—the cells that are organized into proper units, and the material surrounding the cells, called the extracellular matrix (ECM). A third, frequently overlooked feature essential to the maintenance of the activity of the engineered tissue is the three-dimensional architecture of the cell-matrix composite.A comprehensive review of the scope and impact of tissue engineering has previously appeared. Tissue-engineered devices have the potential to reduce the annual health-care cost related to tissue loss and end-stage organ failure to the order of $400 billion, eight million invasive surgical procedures, and 65 million hospital days. A common approach to engineer a functional tissue is to place cells derived from a healthy organ or tissue type (identical or similar to the dysfunctional tissue/organ) on or within matrices analogous to host-tissue ECM. These systems can then be enclosed in appropriate membranes that isolate cells from immune rejection following implantation or can be transplanted directly with the administration of drugs that prevent the immune rejection. Another application of these systems is for extracorporeal (outside the patient's body) device support of a dysfunctional organ. In either instance, the success of the engineered tissue depends critically on the interactions of cells with the tissue analogues. The objective of this article is to outline the simplest matrix-design parameters to control these interactions. While organs are comprised of very different tissue types, for the sake of simplicity, this article is primarily pertinent to the tissue engineering of one major organ, the liver. The choice of this tissue type is intended to serve as a comprehensive generalization of many different cell types since in the diversity and complexity of its activities, the liver has few parallels. The development of an artificial liver is also critically awaited, as in the United States alone, 35,000 people, including the many wait listed for the exorbitant liver organ transplants ($300,000), die each year of chronic liver disorders. In many other countries, liver disease is the second leading cause of death.


ASAIO Journal ◽  
2001 ◽  
Vol 47 (2) ◽  
pp. 173
Author(s):  
Shin-ichi Itoi ◽  
Tatsuo Nakamura ◽  
Yasuhiko Shimizu ◽  
Hiroshi Mizuno

2017 ◽  
Vol 15 (1) ◽  
pp. 25-30
Author(s):  
Bogusława Orzechowska-Wylęgała ◽  
Dariusz Dobrowolski ◽  
Domenico Puzzolo ◽  
Bogumił Wowra ◽  
Wiktor Niemiec ◽  
...  

Background The aim of this study was to investigate the application of mucous membrane keratinocyte cultures on amniotic membrane and on poly(L-lactic acid) (PLLA) Purasorb PL38 to cover tissue loss in the oral cavity. Developments in molecular biology techniques and tissue engineering allow the culturing and identification of cells that can be anchored in the wound to achieve integrity of the tissue. Transplantation of tissues obtained from the patient's own cells is superior to allogenous transplantation where there is a possibility of transfection, rejection and the need for long-term immunosuppression. Methods In 9 patients (15 procedures) keratinocytes cultured on amniotic membrane and PLLA were transplanted to cover antro-oral fistulas and bone loss after osteoradionecrosis. Results In all 6 patients with outlasting antro-oral fistulas, the defects were healed. In 3 patients with 5 cases of tissue loss after osteoradionecrosis, we obtained healing of the wound in only 1 case. Histological examination of the cultures indicated that cultured cells formed well-differentiated layers, very similar to the keratinocytes of mucous membranes, although those seeded on amniotic membrane formed a single layer of cells, while those seeded on the PLLA scaffold were arranged on 2 or more layers: these differences were shown to be statistically significant with a morphometric analysis. Conclusions Autologous transplants of epithelium cultured on amniotic membrane and PLLA constitute a new and effective way of covering nonhealing tissue loss in the oral cavity in chosen cases, using modern methods of tissue engineering.


2007 ◽  
Vol 103 (2) ◽  
pp. 710-716 ◽  
Author(s):  
Michael J. Emery ◽  
Randy L. Eveland ◽  
Seong S. Kim ◽  
Jacob Hildebrandt ◽  
Erik R. Swenson

CO2 regulation of lung compliance is currently explained by pH- and CO2-dependent changes in alveolar surface forces and bronchomotor tone. We hypothesized that in addition to, but independently of, those mechanisms, the parenchyma tissue responds to hypercapnia and hypocapnia by relaxing and contracting, respectively, thereby improving local matching of ventilation (V̇a) to perfusion (Q̇). Twenty adult rats were slowly ventilated with modified Krebs solution (rate = 3 min−1, 37°C, open chest) to produce unperfused living lung preparations free of intra-airway surface forces. The solution was gassed with 21% O2, balance N2, and CO2 varied to produce alveolar hypocapnia (Pco2 = 26.1 ± 2.4 mmHg, pH = 7.56 ± 0.04) or hypercapnia (Pco2 = 55.0 ± 2.3 mmHg, pH = 7.23 ± 0.02). The results show that lung recoil, as indicated from airway pressure measured during a breathhold following a large volume inspiration, is reduced ∼30% when exposed to hypercapnia vs. hypocapnia ( P < 0.0001, paired t-test), but stress relaxation and flow-dependent airway resistance were unaltered. Increasing CO2 from hypo- to hypercapnic levels caused a substantial, significant decrease in the quasi-static pressure-volume relationship, as measured after inspiration and expiration of several tidal volumes, but hysteresis was unaltered. Furthermore, addition of the glycolytic inhibitor NaF abolished CO2 effects on lung recoil. The results suggest that lung parenchyma tissue relaxation, arising from active elements in response to increasing alveolar CO2, is independent of (and apparently in parallel with) passive tissue elements and may actively contribute to V̇a/Q̇ matching.


2020 ◽  
Vol 834 ◽  
pp. 162-168
Author(s):  
Michala Rampichová ◽  
Vera Lukášová ◽  
Matej Buzgo ◽  
Karolína Vocetková ◽  
Vera Sovková ◽  
...  

Skeletal disorders, caused by trauma, disease, or carcinoma, may result in tissue loss and, finally, in endoprosthesis. Tissue engineering offers an alternative - tissue scaffolds. Its constructs may be seeded with autologous cells or, alternatively, attract cells from the surrounding tissues. Such a scaffold must meet several requirements, such as biocompatibility, biodegradability and suitable morphology for cell attachment and proliferation. Nonetheless, scaffold should stimulate cells migrated from the surrounding tissues to infiltrate the scaffold, proliferate and differentiate to the required cell type. In the current study, we developed a fibrous scaffold with 3D structure using emulsion centrifugal spinning. The scaffold from poly-ɛ-caprolactone contained a cocktail of growth factors, i.e. TGF-β, IGF and bFGF. The released growth factors enhanced cell proliferation and chondrogenic differentiation. The scaffold is a promising material for skeletal tissue engineering.


PLoS ONE ◽  
2011 ◽  
Vol 6 (2) ◽  
pp. e16726 ◽  
Author(s):  
Marina Martinez ◽  
Jean-Michel Brezun ◽  
Christian Xerri
Keyword(s):  

2021 ◽  
Vol 12 ◽  
pp. 204173142110037
Author(s):  
Aala’a Emara ◽  
Rishma Shah

The craniofacial region consists of several different tissue types. These tissues are quite commonly affected by traumatic/pathologic tissue loss which has so far been traditionally treated by grafting procedures. With the complications and drawbacks of grafting procedures, the emerging field of regenerative medicine has proved potential. Tissue engineering advancements and the application in the craniofacial region is quickly gaining momentum although most research is still at early in vitro/in vivo stages. We aim to provide an overview on where research stands now in tissue engineering of craniofacial tissue; namely bone, cartilage muscle, skin, periodontal ligament, and mucosa. Abstracts and full-text English articles discussing techniques used for tissue engineering/regeneration of these tissue types were summarized in this article. The future perspectives and how current technological advancements and different material applications are enhancing tissue engineering procedures are also highlighted. Clinically, patients with craniofacial defects need hybrid reconstruction techniques to overcome the complexity of these defects. Cost-effectiveness and cost-efficiency are also required in such defects. The results of the studies covered in this review confirm the potential of craniofacial tissue engineering strategies as an alternative to avoid the problems of currently employed techniques. Furthermore, 3D printing advances may allow for fabrication of patient-specific tissue engineered constructs which should improve post-operative esthetic results of reconstruction. There are on the other hand still many challenges that clearly require further research in order to catch up with engineering of other parts of the human body.


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