Tissue engineering in plastic and reconstructive surgery: fostering advances in the 21st century via an understanding of the present state of the art and future possibilities

Manish Anand,Manish Bhagania,Kiranmeet Kaur 대한미용성형외과학회 2023 Archives of Aesthetic Plastic Surgery Vol.29 No.2

Tissue engineering is a subfield of regenerative medicine that has been hailed as the most cutting-edge medical and surgical achievement to date. Tissue engineering aims to restore or construct whole tissues that have been lost due to congenital disabilities, trauma, or surgery. Tissue engineering is based on the premise of obtaining mesenchymal stem cells that can be used to create an embryologically comparable organ. To regenerate an organ that resembles the intended tissue to be replaced, a complex synergistic interplay between stem cells, signaling molecules, and scaffold, is required. Tissue engineering in plastic surgery is expected to reduce surgical morbidity by integrating cell signals or bio-artificial components taken from the patient’s cells, which may replace damaged bodily tissue without the need for extensive reconstructive surgery. With the advent of 3-dimensional printers for modeling scaffolds and current tissue engineering methods for the regeneration of muscle, bone, and cartilage in the laboratory, the scope of tissue engineering is no longer confined to cells and scaffolds, but also encompasses growth factors and cytokines. Although these methods seem promising, clinical success has been limited to essential tissue regeneration, with considerable difficulties remaining to overcome. This paper aims to introduce readers to tissue engineering’s existing breadth, regeneration processes, limits, and prospects.

Recent advances in stem cell therapeutics and tissue engineering strategies

권성규,권양우,이태욱,박규태,김재호 한국생체재료학회 2018 생체재료학회지 Vol.22 No.4

Background: Tissue regeneration includes delivering specific types of cells or cell products to injured tissues or organs for restoration of tissue and organ function. Stem cell therapy has drawn considerable attention since transplantation of stem cells can overcome the limitations of autologous transplantation of patient’s tissues; however, it is not perfect for treating diseases. To overcome the hurdles associated with stem cell therapy, tissue engineering techniques have been developed. Development of stem cell technology in combination with tissue engineering has opened new ways of producing engineered tissue substitutes. Several studies have shown that this combination of tissue engineering and stem cell technologies enhances cell viability, differentiation, and therapeutic efficacy of transplanted stem cells. Main body: Stem cells that can be used for tissue regeneration include mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells. Transplantation of stem cells alone into injured tissues exhibited low therapeutic efficacy due to poor viability and diminished regenerative activity of transplanted cells. In this review, we will discuss the progress of biomedical engineering, including scaffolds, biomaterials, and tissue engineering techniques to overcome the low therapeutic efficacy of stem cells and to treat human diseases. Conclusion: The combination of stem cell and tissue engineering techniques overcomes the limitations of stem cells in therapy of human diseases, and presents a new path toward regeneration of injured tissues.

The Effect of Cultured Perichondrial Cell Sheet Covered Highly Active Engineered Cartilage: in vivo Comparative Assessment

박세일,문영미,정재호,장광호,안면환 한국임상수의학회 2011 한국임상수의학회지 Vol.28 No.5

A special mesenchymal tissue layer called perichondrium has a chondrogenic capacity and is a candidate tissue for engineering of cartilage. To overcome limited potential for chondrocyte proliferation and re-absorption, we studied a method of cartilage tissue engineering comprising chondrocyte-hydrogel pluronic complex (CPC) and cultured perichondrial cell sheet (cPCs) which entirely cover CPC. For effective cartilage regeneration, cell-sheet engineering technique of high-density culture was used for fabrication of cPCs. Hydrogel pluronic as a biomimetic cell carrier used for stable and maintains the chondrocytes. The human cPCs was cultured as a single layer and entirely covered CPC. The tissue engineered constructs were implanted into the dorsal subcutaneous tissue pocket on nude mice (n = 6). CPC without cPCs were used as a controls (N = 6). Engineered cartilage specimens were harvested at 12 weeks after implantation and evaluated with gross morphology and histological examination. Biological analysis was also performed for glycosaminoglycan (GAG) and type II collagen. Indeed, we performed additional in vivo studies of cartilage regeneration using canine large fullthickness chondrial defect model. The dogs were allocated to the experimental groups as treated chondrocyte sheets with perichondrial cell sheet group (n = 4), and chondrocyte sheets only group (n = 4). The histological and biochemical studies performed 12 weeks later as same manners as nude mouse but additional immunofluorescence study. Grossly, the size of cartilage specimen of cPCs covered group was larger than that of the control. On histological examination, the specimen of cPCs covered group showed typical characteristics of cartilage tissue. The contents of GAG and type II collagen were higher in cPCs covered group than that of the control. These studies demonstrated the potential of such CPC/cPCs constructs to support chondrogenesis in vivo. In conclusion, the method of cartilage tissue engineering using cPCs supposed to be an effective method with higher cartilage tissue gain. We suggest a new method of cartilage tissue engineering using cultured perichondrial cell sheet as a promising strategy for cartilage tissue reconstruction. 조직공학적 인공연골재생에 대한 관심이 증가함에 따라 많은 연구들이 활발히 수행되고 있으나 임상적인 적용의 한계를 극복하기위한 고효능을 보유한 양질의 연골조직생산의 필요성이 증가되고 있다. 인공연골은 자연연골과는 달리 ‘연골막(perichondrium)’을 포함하고 있지 않기 때문에 장기간 생체 내에 삽입된 후에 서서히 흡수 또는 변형으로 임상적 활용에 한계가 있다고 있다. 이에 본 연구는 양질의 연골조직생산을 목적으로, 세포판 제작기법(cell sheet engineering technique) 을 기반으로 한 인체유래의 배양 연골막(cultured perichondrium)을 이용하여 만든 인공연골막세포판(cultured perichondrial cell sheet)의 생체 내 특성을 비교 분석하고, 배양된 연골막을 피복하여 고효능화를 유도한 인공연골복합체의 생체내 재생효능 및 조직특성을 비교 평가하고자 하였다. 본 연구에서는 thymic nude mouse 의 피하이식모델(study 1, n = 12)을 이용하여 담체로 hydrogel을 이용한 배양연골막 복합체의 생체내 효능을 분석하였고, 중대형동물의 대량연골 결손시의 재생효능을 평가하기 위하여 개의 무릎연골에 1 × 2 cm의 대량연골 결손모델(study 2, n = 12)을 통하여 인공배양세포판을 이식하였다. 이식12주 후 이식편을 회수하여 생화학, 분자생물학 및 면역조직학 분석을 시행한 결과, 배양연골막 복합체의 생체내 효능이 단독이식군에 비해 변형이나 과증식 없이 우수한 결과를 나타내었다. 본 연구의 결과로 토대로 배양연골막을 피복한 인공연골막의 관절내 효과를 규명하여 실제 임상적용을 조기화하는 기반을 제공하고 인공연골의 문제점이었던 변형과 흡수를 줄인 고효능 인공연골 제작기법을 제공하는데 유용할 것으로 기대된다.

Strategies for Constructing Tissue-Engineered Fat for Soft Tissue Regeneration

Zhao Jing,Lu Feng,Dong Ziqing 한국조직공학과 재생의학회 2024 조직공학과 재생의학 Vol.21 No.3

Background: Repairing soft tissue defects caused by inflammation, tumors, and trauma remains a major challenge for surgeons. Adipose tissue engineering (ATE) provides a promising way to solve this problem. Methods: This review summarizes the current ATE strategies for soft tissue reconstruction, and introduces potential construction methods for ATE. Results: Scaffold-based and scaffold-free strategies are the two main approaches in ATE. Although several of these methods have been effective clinically, both scaffold-based and scaffold-free strategies have limitations. The third strategy is a synergistic tissue engineering strategy and combines the advantages of scaffold-based and scaffold-free strategies. Conclusion: Personalized construction, stable survival of reconstructed tissues and functional recovery of organs are future goals of building tissue-engineered fat for ATE. Background: Repairing soft tissue defects caused by inflammation, tumors, and trauma remains a major challenge for surgeons. Adipose tissue engineering (ATE) provides a promising way to solve this problem. Methods: This review summarizes the current ATE strategies for soft tissue reconstruction, and introduces potential construction methods for ATE. Results: Scaffold-based and scaffold-free strategies are the two main approaches in ATE. Although several of these methods have been effective clinically, both scaffold-based and scaffold-free strategies have limitations. The third strategy is a synergistic tissue engineering strategy and combines the advantages of scaffold-based and scaffold-free strategies. Conclusion: Personalized construction, stable survival of reconstructed tissues and functional recovery of organs are future goals of building tissue-engineered fat for ATE.

Adipose Tissue: A Valuable Resource of Biomaterials for Soft Tissue Engineering

최지숙,조용우,최영찬,김재동,김은지,이희용,권익찬 한국고분자학회 2014 Macromolecular Research Vol.22 No.9

Extracellular matrices (ECMs), isolated through decellularization of mammalian tissues, have been successfullyused in a variety of tissue engineering and regenerative medicine applications. The composition and spatialstructure of ECMs provide not only specific instructive cues for the growth, migration, and differentiation of variouscells in vitro, but afford ideal substrates for in vivo tissue reconstruction. Adipose tissue, which is the most prevalentand expendable tissue in the body and can be harvested in large quantities with minimal morbidity, has received muchattention as a rich source of ECMs. Recent studies have designed different processes to isolate intact ECMs fromadipose tissue and have fabricated various three-dimensional (3-D) tissue engineering scaffolds such as microparticles,powders, sponges, sheets, and hydrogels for use in regenerative medicine, particularly for patients requiringsoft tissue regeneration. Indeed, because of the abundance of ECM components within adipose tissue, combinedwith the relative ease of large tissue harvesting, adipose tissue is a valuable resource in tissue regeneration therapy,encompassing autotransplantation, allotransplantation, and xenotransplantion. We briefly review extraction anddecellularization techniques of ECMs from adipose tissue, biological characterization and fabrication of ECM-basedtissue engineering scaffolds, and their use in soft tissue engineering.

Bone Tissue Engineering Using Marrow Stromal Cells

Jo, In-Ho,Lee, Jung-Min,Suh, Hwal,Kim, Hyong-Bum Korean Society for Biotechnology and Bioengineerin 2007 Biotechnology and Bioprocess Engineering Vol.12 No.1

Bone tissue defects cause a significant socioeconomic problem, and bone is the most frequently transplanted tissue beside blood. Autografting is considered the gold standard treatment for bone defects, but its utility is limited due to donor site morbidity. Hence, much research has focused on bone tissue engineering as a promising alternative method for repair of bone defects. Marrow stromal cells (MSCs) are considered to be potential cell sources for bone tissue engineering. In bone tissue engineering using MSCs, bone is formed through intramembranous and endochondral ossification in response to osteogenic inducers. Angiogenesis is a complex process mediated by multiple growth factors and is crucial for bone regeneration. Vascular endothelial growth factor plays important roles in bone tissue regeneration by promoting the migration and differentiation of osteoblasts, and by inducing angiogenesis. Scaffold materials used for bone tissue engineering include natural components of bone, such as calcium phosphate and collagen I, and biodegradable polymers such as poly(lactide-coglycolide). However, ideal scaffolds for bone tissue engineering have yet to be found. Bone tissue engineering has been successfully used to treat bone defects in several human clinical trials to regenerate bone defects. Through investigation of MSC biology and the development of novel scaffolds, we will be able to develop advanced bone tissue engineering techniques in the future.

Review: Scaffold Characteristics, Fabrication Methods, and Biomaterials for the Bone Tissue Engineering

Jae-Won Jang,Kyung-Eun Min,Cheolhee Kim,Jesik Shin,Jiwoon Lee,Sung Yi 한국정밀공학회 2023 International Journal of Precision Engineering and Vol.24 No.3

The goal of tissue engineering is to replace or regenerate damaged tissue. Scaffold fabrications and biomaterial selections are crucial factors for artificial tissue and bone tissue engineering, which are important due to the limited availability of tissue donors. This paper reviews the scaffold design considerations, manufacturing methods, and biomaterials for bone tissue engineering, and discusses current challenges and future perspectives. Scaffolds are required to have non-hazardous properties such as biocompatibility and biodegradability for the human body, and the necessary mechanical properties to support body weight, or to perform other roles, depending on the type of tissue. Moreover, scaffold structures such as porosity, pore size, and pore shape should be optimized to achieve cell viability and proliferation. Many conventional fabrication methods including thermally induced phase separation, emulsion freeze-drying, solvent casting, gas forming, and electrospinning have been studied and developed, but 3D printing is more suitable for bone tissue engineering because of its ability to manufacture complicated structures. Biomaterials can be divided into four categories: polymer, ceramic, metal, and composites. Composites blend two or more biomaterials to achieve desired properties for matching individual patient conditions. Finding a balance between fabrication method and biomaterial selection, in order to match properties between the scaffold and the target tissue, will be key to the field of bone tissue engineering in the future.

Novel Perfusion Bioreactor Systems for Tissue Engineering

임기택,조종수,정연훈,김장호,선우훈,백수정,전성후,박주영,정필훈,정종훈,손현목 한국조직공학과 재생의학회 2009 조직공학과 재생의학 Vol.6 No.1

Bioreactor systems that use a new aeration concept have recently been introduced. Bioreactors can assist in the development of new tissues in vitro by providing appropriate stimuli to the cell cultures. The design of bioreactors for tissue engineering is very complex and is often tailored to individual cell- engineered-tissue products. Critical elements in bioreactor systems based on cells and scaffolds include cell seeding, the nutrient and gas supply to cells, and mechanical stimuli. Flow perfusion systems have been shown to enhance cell growth, differentiation, and tissue formation as well as provide for the appropriate and necessary mass transfer of nutrients, gases, metabolites, and regulatory molecules. The beneficial effects of fluid flow induced convective transport and shear stress have been exploited in various types of bioreactors because fluid flow-through cell and tissue engineered constructs increase nutrient transport. These systems are called flow-perfusion bioreactors. In this paper, we review the characteristics of bioreactor systems used for cell culture in tissue engineering, and provide a schematic design for a novel bioreactor system that incorporates the elements we deem critical for such systems. Bioreactor systems that use a new aeration concept have recently been introduced. Bioreactors can assist in the development of new tissues in vitro by providing appropriate stimuli to the cell cultures. The design of bioreactors for tissue engineering is very complex and is often tailored to individual cell- engineered-tissue products. Critical elements in bioreactor systems based on cells and scaffolds include cell seeding, the nutrient and gas supply to cells, and mechanical stimuli. Flow perfusion systems have been shown to enhance cell growth, differentiation, and tissue formation as well as provide for the appropriate and necessary mass transfer of nutrients, gases, metabolites, and regulatory molecules. The beneficial effects of fluid flow induced convective transport and shear stress have been exploited in various types of bioreactors because fluid flow-through cell and tissue engineered constructs increase nutrient transport. These systems are called flow-perfusion bioreactors. In this paper, we review the characteristics of bioreactor systems used for cell culture in tissue engineering, and provide a schematic design for a novel bioreactor system that incorporates the elements we deem critical for such systems.

Feature Article : Mechanical Stimulation of Mesenchymal Stem Cells for Tissue Engineering

( Jang Ho Kim ),( Chong Su Cho ),( Yun Hoon Choung ),( Ki Taek Lim ),( Hyun Mok Son ),( Hoon Seon Woo ),( Soo Jung Baik ),( Soung Hoo Jeon ),( Joo Young Park ),( Pill Hoon Choung ),( Jong Hoon Chung ) 한국조직공학과 재생의학회 2009 조직공학과 재생의학 Vol.6 No.1

Tissue engineering is a rapidly growing field that utilizes cell/scaffolds constructs with chemical signaling molecules as potential therapeutic products for tissue regeneration. Mesenchymal stem cells(MSCs) provide excellent novel strategies for tissue engineering application. Recently, it has been recognized that understanding mechanical stimulation is an important key to the development of efficient and controllable methods as well as chemical signaling for differentiation of MSCs and tissue engineering application. Especially, a number of studies indicated that the mechanical stimuli can enhance the synergy effects for differentiation of MSCs and tissue formation or regeneration. In this review, we introduced the various mechanical stimuli techniques, the effects of mechanical stimuli to MSCs, and tissue engineering applications. Furthermore, we discussed the further research directions of MSCs and mechanical stimuli based on this review for tissue engineering.

Polycaprolactone/Gelatin/Polypyrrole/Graphene Conductive Aligned Fibrous Scaffold with Ferulic Acid Encapsulation for Tissue Engineering Applications

Alireza Talebi,Pegah Madani Nasab,Sheyda Labbaf,Paul Roach 한국섬유공학회 2023 Fibers and polymers Vol.24 No.9

Tissue engineering approaches aim to overcome the limitations of organ transplants and facilitate tissue repair and regeneration, with demand now at a worldwide high for advanced therapies due to our global aging population. Neural tissue engineering is challenging with tissue dynamics and cellular complexity constraints necessary for tissue function. Here, a conductive, highly aligned, fibrous polycaprolactone/gelatin/polypyrrole/graphene scaffold is demonstrated for potential nerve tissue repair. A simple and efficient electrospinning technique with a rotating drum fabrication approach is utilized to create aligned fibrous structures with a diameter of 380 ± 37 nm (no graphene) to 265 ± 30 nm (up to 3 wt% graphene). The conductivity of the scaffold in wet conditions was found range from 0.76 ± 0.1 S m-1 with no graphene, to 3.96 ± 0.2 S m-1 with 3% wt graphene, with corresponding ultimate tensile strengths measuring 2.6 ± 0.1-5.5 ± 0.4 MPa, respectively. Samples were found to biodegrade during incubation in saline solution over 42 days by ~ 48.5%. Fibroblasts were used as a cell model to test for scaffold toxicity, with all samples presenting good cell adhesion and limited cytotoxicity. Overall, the results demonstrated an aligned fibrous platform with good mechanical and electrically conductive properties useful for tissue engineering applications, particularly for nerve tissue. Development of novel materials with a range of properties enabling optimization of cell adhesion through to tissue development will further support the development of regenerative medicine approaches.