Designing porous scaffolds for tissue engineering

Author(s):  
William Bonfield

Biomaterials are either modified natural or synthetic materials, with an appropriate response in the host tissue, which find application in a wide spectrum of implants and prostheses used in reconstructive medicine. The subsequent integration and longevity of the implanted device depends on the effectiveness of the associated biological repair. Hence, there has been considerable interest in the development of novel, second generation, biomaterials, which are favourably bioactive in terms of promoting the desired cellular response in vivo . Such biomaterials in a porous form can also act as cellular scaffolds and allow in vitro , as well as in vivo incorporation of the appropriate tissue cells, with potential control of the sequence of cell attachment, proliferation and the production of extra-cellular matrix. Such generic tissue engineering depends critically on the porous architecture of the biomaterial scaffold so as to allow both the cellular ingress and vascularization required to create a living tissue. The particular requirements of tissue-engineering scaffolds with respect to macro- and micro-porosity, as well as chemistry, are reviewed.

Author(s):  
I. M. Sebastine ◽  
D. J. Williams

Tissue engineering aims to restore the complex function of diseased tissue using cells and scaffold materials. Tissue engineering scaffolds are three-dimensional (3D) structures that assist in the tissue engineering process by providing a site for cells to attach, proliferate, differentiate and secrete an extra-cellular matrix, eventually leading cells to form a neo-tissue of predetermined, three-dimensional shape and size. For a scaffold to function effectively, it must possess the optimum structural parameters conducive to the cellular activities that lead to tissue formation; these include cell penetration and migration into the scaffold, cell attachment onto the scaffold substrate, cell spreading and proliferation and cell orientation. In vivo, cells are organized in functional tissue units that repeat on the order of 100 μm. Fine scaffold features have been shown to provide control over attachment, migration and differentiation of cells. In order to design such 3D featured constructs effectively understanding the biological response of cells across length scales from nanometer to millimeter range is crucial. Scaffold biomaterials may need to be tailored at three different length scales: nanostructure (<1μm), microstructure (<20–100μm), and macrostructure (>100μm) to produce biocompatible and biofunctional scaffolds that closely resemble the extracellular matrix (ECM) of the natural tissue environment and promote cell adhesion, attachment, spreading, orientation, rate of movement, and activation. Identification of suitable fabrication techniques for manufacturing scaffolds with the required features at multiple scales is a significant challenge. This review highlights the effect and importance of the features of scaffolds that can influence the behaviour of cells/tissue at different length scales in vitro to increase our understanding of the requirements for the manufacture of functional 3D tissue constructs.


2021 ◽  
Author(s):  
Sajad Bahrami ◽  
Nafiseh Baheiraei ◽  
Mostafa Shahrezaee

Abstract Variety of bone-related diseases and injures and limitations of traditional regeneration methods need to introduce new tissue substitutes. Tissue engineering and regeneration combined with nanomedicine can provide different natural or synthetic and combined scaffolds with bone mimicking properties for implant in the injured area. In this study, we synthesized collagen (Col) and reduced graphene oxide coated collagen (Col-rGO) scaffolds and evaluated their in vitro and in vivo effects on bone tissue repair. Col and Col-rGO scaffolds were synthesized by chemical crosslinking and freeze-drying methods. The surface topography, mechanical and chemical properties of scaffolds were characterized and showed three-dimensional (3D) porous scaffolds and successful coating of rGO on Col. rGO coating enhanced mechanical strength of Col-rGO scaffolds compared with Col scaffolds by 2.8 folds. Furthermore, Col-rGO scaffolds confirmed that graphene addition not only did not any cytotoxic effects but also enhanced human bone marrow-derived mesenchymal stem cells (hBMSCs) viability and proliferation with 3D adherence and expansion. Finally, scaffolds implantation into rabbit cranial bone defect for 12 weeks showed increased bone formation, confirmed by Hematoxylin-Eosin (H&E) and alizarin red staining. Altogether, the study showed that rGO coating improves Col scaffold properties and could be a promising implant for bone injuries.


Materials ◽  
2021 ◽  
Vol 14 (17) ◽  
pp. 4777
Author(s):  
Anuj Kumar ◽  
Sung-Soo Han

Bacterial nanocellulose (BNC, as exopolysaccharide) synthesized by some specific bacteria strains is a fascinating biopolymer composed of the three-dimensional pure cellulosic nanofibrous matrix without containing lignin, hemicellulose, pectin, and other impurities as in plant-based cellulose. Due to its excellent biocompatibility (in vitro and in vivo), high water-holding capacity, flexibility, high mechanical properties, and a large number of hydroxyl groups that are most similar characteristics of native tissues, BNC has shown great potential in tissue engineering applications. This review focuses on and discusses the efficacy of BNC- or BNC-based biomaterials for hard tissue regeneration. In this review, we provide brief information on the key aspects of synthesis and properties of BNC, including solubility, biodegradability, thermal stability, antimicrobial ability, toxicity, and cellular response. Further, modification approaches are discussed briefly to improve the properties of BNC or BNC-based structures. In addition, various biomaterials by using BNC (as sacrificial template or matrix) or BNC in conjugation with polymers and/or fillers are reviewed and discussed for dental and bone tissue engineering applications. Moreover, the conclusion with perspective for future research directions of using BNC for hard tissue regeneration is briefly discussed.


Author(s):  
Qingwei Zhang ◽  
Wei Zhang ◽  
Jephte Augustin ◽  
Donggang Yao ◽  
David M. Wootton ◽  
...  

Tissue engineering is a rapidly growing interdisciplinary field which offers a promising new technology to create artificial constructs for regeneration of tissues. One important aspect of bone tissue engineering is to build scaffolds with interconnected 3-D porous structure in order to mimic natural bone architecture. In this work, co-continuous micro-porous scaffolds made of Poly-L-lactic acid (PLLA) with 50% porosity and PLLA/hydroxyapatite (HA) with 40% porosity were prepared by injection molding of an immiscible polymer blend with polystyrene as sacrificial material. The sacrificial material was then removed by solvent leaching with cyclohexane. The porous PLLA/HA matrix supported murine osteoblast (7F2) cell growth for up to 9 days, suggesting that that the introduction and replacement of sacrificial material had no negative effects on cell proliferation. In vitro studies also indicate an increase in mineralization by osteoblasts cultured on the porous structure, as compared to cells cultured on solid scaffold. One month subcutaneous degradation tests showed a mild foreign body reaction and complete fibrous encapsulation. Following surgical implantation of the scaffolds into circular defects in canine tibia, we observed after 12 weeks new bone tissue grew into the porous structures. Taken together our data suggest that interconnected porous structures with good cytocompatibility and increased mineralization in vitro paired with enhanced osteoinductive properties in vivo suggest a great potential of the porous PLLA/HA for inducing and sustaining bone tissue repair.


2012 ◽  
Vol 2 (3) ◽  
pp. 366-377 ◽  
Author(s):  
Zhen Pan ◽  
Jiandong Ding

Porous scaffolds fabricated from biocompatible and biodegradable polymers play vital roles in tissue engineering and regenerative medicine. Among various scaffold matrix materials, poly(lactide- co -glycolide) (PLGA) is a very popular and an important biodegradable polyester owing to its tunable degradation rates, good mechanical properties and processibility, etc. This review highlights the progress on PLGA scaffolds. In the latest decade, some facile fabrication approaches at room temperature were put forward; more appropriate pore structures were designed and achieved; the mechanical properties were investigated both for dry and wet scaffolds; a long time biodegradation of the PLGA scaffold was observed and a three-stage model was established; even the effects of pore size and porosity on in vitro biodegradation were revealed; the PLGA scaffolds have also been implanted into animals, and some tissues have been regenerated in vivo after loading cells including stem cells.


2018 ◽  
Vol 65 (1) ◽  
pp. 37-44
Author(s):  
Dijana Trišić ◽  
Vukoman Jokanović ◽  
Đorđe Antonijević ◽  
Dejan Marković

Summary Stem cells have shown great potential for in vitro tissue engineering, regenerative medicine, cell therapy and pharmaceutical applications. All these applications, especially in clinical trials, will require guided production of high-quality cells. Traditional culture techniques and applications have been performed for the majority of primary and established cell lines and standardized for various analyses. Still, these culture conditions are unable to mimic dynamic and specialized three-dimensional microenvironment of the stem cells’ niche from in vivo conditions. In an attempt to provide biomimetic microenvironments for stem cells in vitro growth, three-dimensional culture techniques have been developed. In our study advantages of newly developed porous scaffolds as the most promising in vitro imitation of niche that provides physical support, enables cell growth, regeneration and neovascularization, while they are replaced in time with newly created tissue was explained. Furthermore, dynamic cultivation techniques have been described, as new way of cell culturing that will be the main subject of our future research. In that manner, by developing an optimal dynamic culturing method, high-quality new cells and tissues would be possible to obtain, for any future clinical application.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Weigang Li ◽  
Chunwei Huang ◽  
Tian Ma ◽  
Jiachen Wang ◽  
Wenbin Liu ◽  
...  

Abstract Background Intervertebral fusion is the most common surgery to treat lumbar degenerative disease (LDD). And the graft material used in the operation is derived from the iliac crest to promote fusion. However, autografts possess the fatal disadvantage of lack of source. Therefore, economical and practical bone substitutes are urgently needed to be developed. Sinusoidal electromagnetic fields (EMF) combined with tissue engineering techniques may be an appropriate way to promote intervertebral fusion. Methods In this research, porous scaffolds made of polycaprolactone (PCL) and nano-hydroxyapatite (nHA) were used as cell carriers. Then, the scaffolds loaded with bone marrow mesenchymal stem cells (BMSCs) were treated with sinusoidal electromagnetic field and the osteogenic capability of BMSCs was tested later. In addition, an intervertebral disc of the tail vertebra of the rat was removed to construct a spinal intervertebral fusion model with a cell-scaffold implanted. The intervertebral fusion was observed and analyzed by X-ray, micro-CT, and histological methods. Results BMSCs stimulated by EMF possess splendid osteogenic capability under an osteogenic medium (OM) in vitro. And the conditioned medium of BMSCs treated with EMF can further promote osteogenic differentiation of the primitive BMSCs. Mechanistically, EMF regulates BMSCs via BMP/Smad and mitogen-activated protein kinase (MAPK)-associated p38 signaling pathways. In vivo experiments revealed that the scaffold loaded with BMSCs stimulated by EMF accelerated intervertebral fusion successfully. Conclusion In summary, EMF accelerated intervertebral fusion by improving the osteogenic capacity of BMSCs seeded on scaffolds and might boost the paracrine function of BMSCs to promote osteogenic differentiation of the homing BMSCs at the injured site. EMF combined with tissue engineering techniques may become a new clinical treatment for LDD.


2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Caterina Cristallini ◽  
Elisa Cibrario Rocchietti ◽  
Mariacristina Gagliardi ◽  
Leonardo Mortati ◽  
Silvia Saviozzi ◽  
...  

The biomaterial scaffold plays a key role in most tissue engineering strategies. Its surface properties, micropatterning, degradation, and mechanical features affect not only the generation of the tissue construct in vitro, but also its in vivo functionality. The area of myocardial tissue engineering still faces significant difficulties and challenges in the design of bioactive scaffolds, which allow composition variation to accommodate divergence in the evolving myocardial structure. Here we aimed at verifying if a microstructured bioartificial scaffold alone can provoke an effect on stem cell behavior. To this purpose, we fabricated microstructured bioartificial polymeric constructs made of PLGA/gelatin mimicking anisotropic structure and mechanical properties of the myocardium. We found that PLGA/gelatin scaffolds promoted adhesion, elongation, ordered disposition, and early myocardial commitment of human mesenchymal stem cells suggesting that these constructs are able to crosstalk with stem cells in a precise and controlled manner. At the same time, the biomaterial degradation kinetics renders the PLGA/gelatin constructs very attractive for myocardial regeneration approaches.


2007 ◽  
Vol 361-363 ◽  
pp. 931-934 ◽  
Author(s):  
Conor T. Buckley ◽  
K.U. O’Kelly

Tissue-engineering scaffold-based strategies have suffered from limited cell depth viability when cultured in vitro, with viable cells existing within the outer 250-500μm from the fluid-scaffold interface. This is primarily believed to be due to the lack of nutrient delivery into and waste removal from the inner regions of the scaffold construct. Other issues associated with porous scaffolds involve poor seeding efficiencies and limited cell penetration resulting in heterogeneous cellular distributions. This work focuses on the development a novel hydroxyapatite multi-domain porous scaffold architecture (i.e. a scaffold providing a discrete domain for cell occupancy and a separate domain for nutrient delivery) with the specific objectives of embodying in one scaffold the structures required to optimise cell seeding, cell proliferation and migration and potentially to facilitate vascularisation once implanted in vivo. This paper presents the development of the multidomain architecture and preliminary results on cell viability which show a significant improvement in cell viability in the scaffold interiors.


2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.


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