Design and 3D Printing of Hierarchical Tissue Engineering Scaffolds Based on Mechanics and Biology Perspectives

Author(s):  
Paul Egan ◽  
Stephen J. Ferguson ◽  
Kristina Shea

Continued scientific research is crucial for developing new biomedical products, such as tissue engineering scaffolds, that are difficult to optimize due to the complexity of interfacing mechanical and biological systems. In this paper, mechanical and biological perspectives are used to propose and implement an approach for designing hierarchical scaffolds that provide structural support in the body as tissue regenerates. Three sequential steps are proposed for defining design needs, generating design alternatives, and fabricating design prototypes. Design needs are determined by considering mechanical and biological performance requirements, experimental procedures, and fabrication constraints. The primary mechanical requirement is a scaffold’s need to maintain structural integrity, while biologically the scaffold should promote cellular growth. Scaffold design alternatives of four topology types are generated by altering design parameters that describe a scaffold’s structure. Trade-offs are revealed for scaffold porosity and surface area properties that are known to influence mechanical and biological scaffold performance. Scaffolds of each topology type are designed with 80% porosity and fabricated, which enables their potential use in scientific experiments to measure how property trade-offs influence scaffold performance. On the basis of currently available knowledge, a to-scale spinal scaffold implant is designed and fabricated with a graphically maximized surface area to porosity ratio for a hierarchical scaffold, which represents a potentially high performing design from both mechanical and biological perspectives. These results demonstrate the importance of multidisciplinary approaches for designing complex biomedical tissue scaffolds that could significantly improve healthcare through the development of new clinical products.

Polymers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 3154
Author(s):  
Md Mohosin Rana ◽  
Hector De la Hoz Siegler

Poly(N-isopropylacrylamide) (PNIPAm) is a three-dimensional (3D) crosslinked polymer that can interact with human cells and play an important role in the development of tissue morphogenesis in both in vitro and in vivo conditions. PNIPAm-based scaffolds possess many desirable structural and physical properties required for tissue regeneration, but insufficient mechanical strength, biocompatibility, and biomimicry for tissue development remain obstacles for their application in tissue engineering. The structural integrity and physical properties of the hydrogels depend on the crosslinks formed between polymer chains during synthesis. A variety of design variables including crosslinker content, the combination of natural and synthetic polymers, and solvent type have been explored over the past decade to develop PNIPAm-based scaffolds with optimized properties suitable for tissue engineering applications. These design parameters have been implemented to provide hydrogel scaffolds with dynamic and spatially patterned cues that mimic the biological environment and guide the required cellular functions for cartilage tissue regeneration. The current advances on tuning the properties of PNIPAm-based scaffolds were searched for on Google Scholar, PubMed, and Web of Science. This review provides a comprehensive overview of the scaffolding properties of PNIPAm-based hydrogels and the effects of synthesis-solvent and crosslinking density on tuning these properties. Finally, the challenges and perspectives of considering these two design variables for developing PNIPAm-based scaffolds are outlined.


Author(s):  
Hugh Lippincott ◽  
Daniel F. Schmidt

Shape recovery from memory by porous scaffolds for tissue engineering offers easier insertion and self-retention following placement by minimally invasive surgery. Shape memory testing of porous polymer xerogels focuses on the compression cycle and the special aspects of the cycle and equipment used. This contrasts with normal tensile shape memory (SM) testing. In this work a dynamic mechanical analyzer (DMA) was used on small samples to quickly yield measurement of the SM restoration at various stress levels to emulate the forces exerted on the body by a tissue engineering (TE) scaffold returning to its permanent shape. The DMA testing of a hexamethyl diisocyanate trimer crosslinked castor oil (CO) / polycaprolactone (PCL) blend yielded repeated SM with no creep. The porous CO/PCL showed repeated compressive SM at 50% strain with a SM stress-free recovery ratio of 100%. The peak SM recovery work of 6.4 KJ/m3 was measured at 0.5 MPa stress and 6% to 12% strain. In addition to the potential utility of these materials in a tissue engineering setting, the test methods described here are relevant to a broad range of shape memory applications, from medical devices to morphing airframes to self-deploying structures.


2012 ◽  
Vol 529-530 ◽  
pp. 19-23 ◽  
Author(s):  
G. Daculsi ◽  
Thomas Miramond ◽  
Pascal Borget ◽  
Serge Baroth

The development of CaP ceramics involved a better control of the process of resorption and bone substitution. Micro Macroporous Biphasic CaP, (MBCP+) is a concept based on an optimum balance of the more stable phase of HA and more soluble TCP. The material is soluble and gradually dissolves in the body, seeding new bone formation as it releases Ca and P ions into the biological medium. The MBCP+ is selected for tissue engineering in a large European research program on osteoinduction and mesenchymal stem cell technology (REBORNE 7thEU frame work program, Regenerative Bone defects using New biomedical Engineering approaches,www.reborne.org). We have optimized the matrices in terms of their physical, chemical, and crystal properties, to improve cell colonization and to increase kinetic bone ingrowth. The fast cell colonization and resorption of the material are associated to the interconnected macropores structure which enhances the resorption bone substitution process. The micropore content involves biological fluid diffusion and suitable adsorption surfaces for circulating growth factors. The bioceramics developed for this project was fully characterized using X-Ray diffraction, FTIR, X-rays micro tomography, Hg porosimetry, BET specific surface area, compressive mechanical test, and SEM. Preclinical tests on the optimized scaffold were realized in critical size defects in several sites of implantation and animals (rats, rabbits, goats, dogs).The smart scaffold has a total porosity of 73%, constituted of macropores (>100µm), mesopores of 10 to 100µm and high micropores (<10µm) content of more or less 40%. The crystal size is <0.5 to 1 µm and the specific surface area was around 6m2/g. Thein vivoexperiment indicated higher colonization by osteogenic cells demonstrating suitable matrices for tissue engineering. The HA/TCP ratio of 20/80 was also more efficient for combination with total bone marrow or stem cell cultivation and expansion before to be implanted.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Zuwei Luo ◽  
Qin Zhang ◽  
Meijing Shi ◽  
Yang Zhang ◽  
Wei Tao ◽  
...  

Controlling the degradation rate of silk fibroin-based biomaterial is an important capability for the fabrication of silk-based tissue engineering scaffolds. In this study, scaffolds with different pore sizes were prepared by controlling the freezing temperature and the silk fibroin concentration.In vitrodegradation results showed that the internal pore walls of the scaffolds with a larger pore size collapsed upon exposure to collagenase IA for times ranging from 6 to 12 days, and the silk scaffolds exhibited a faster rate of weight loss. The morphological and structural features of the silk scaffolds with a smaller pore size maintained structural integrity after incubation in the protease solution for 18 days, and the rate of weight loss was relatively slow. Scaffolds with a smaller pore size or a higher pore density degraded more slowly than scaffolds with a larger pore size or lower pore density. These results demonstrate that the pore size of silk biomaterials is crucial in controlling the degradation rate of tissue engineering scaffolds.


Author(s):  
M. Wettergreen ◽  
B. Bucklen ◽  
W. Sun ◽  
M. A. K. Liebschner

Tissue engineering is developing into a less speculative field involving the careful interplay of numerous design parameters and multi-disciplinary professionals. Problem solving abilities and state of the art research tools are required to develop solutions for a wide variety of clinical issues. One area of particular interest is orthopaedic biomechanics, a field that is responsible for the treatment of over 700,000 vertebral fractures in the U.S alone last year. Engineers are currently lacking the technology and knowledge required to govern the subsistence of cells in vivo, let alone the knowledge to create a functional tissue replacement for a whole organ. Despite this, advances in Computer Aided Tissue Engineering (CATE) are continually growing. Using a combinatory approach to scaffold design, patient-specific implants may be constructed. Computer aided design (CAD), optimization of geometry using voxel finite element models or other optimization routines, creation of a library of architectures with specific material properties, rapid prototyping, and determination of a defect site using imaging modalities highlight the current availability of design resources. Our study represents a patient specific approach for constructing a complete vertebral body via building blocks. Though some of the methods described cannot be realized with current technology, namely complete construction of the vertebral body via FDM, the necessary advances are not far off. Computing power and CAD programs need to improve slightly to allow the rapid generation of complex models that would ease the fabrication of an appropriate number of building blocks. The main bottleneck of the process described in this study is the general lack of knowledge of human mechanobiology and the role of cellular interactions on artificial substrates including immune responses, and foreign body reactions. Assuming these biological parameters can be identified, a scaffold may be designed with a proper pore size and interconnectivity, microstructure, degradation rate, and surface chemistry. The advantage of the outlined process lies in adjustment of the vertebral compliance first, to ensure adequate load transfer, an important property for vertebral replacement. Subsequently, net biological properties can be fine tuned by simply scaling the final construct. Mixing and matching of geometries may be utilized to design asymmetric scaffolds, or scaffolds that exhibit a discontinuous microstructural stiffness with the goal of accentuating fluid flow. Finally, while these techniques lend themselves to the formulation of bone constructs, they can be used for other parts of the body as well that do not require load-bearing support.


Author(s):  
Craig Wiltsey ◽  
Thomas Christiani ◽  
Jesse Williams ◽  
Jamie Coulter ◽  
Dana Demiduke ◽  
...  

Tissue engineering is a rapidly growing field of research that aims to repair damaged tissues within the body. Among tissue engineering approaches is the use of scaffolds to help regenerate lost tissues. Scaffolds provide structural support for specific areas within the body, namely load bearing regions, and allow for cells to be seeded within the scaffold for tissue regeneration. Scaffolds that specifically replicate the properties and/or composition of native tissues are referred to as biomimetic scaffolds.


2007 ◽  
pp. S51-S60
Author(s):  
L Koláčná ◽  
J Bakešová ◽  
F Varga ◽  
E Košťáková ◽  
D Lukáš ◽  
...  

ECM is composed of different collagenous and non-collagenous proteins. Collagen nanofibers play a dominant role in maintaining the biological and structural integrity of various tissues and organs, including bone, skin, tendon, blood vessels, and cartilage. Artificial collagen nanofibers are increasingly significant in numerous tissue engineering applications and seem to be ideal scaffolds for cell growth and proliferation. The modern tissue engineering task is to develop three-dimensional scaffolds of appropriate biological and biomechanical properties, at the same time mimicking the natural extracellular matrix and promoting tissue regeneration. Furthermore, it should be biodegradable, bioresorbable and non-inflammatory, should provide sufficient nutrient supply and have appropriate viscoelasticity and strength. Attributed to collagen features mentioned above, collagen fibers represent an obvious appropriate material for tissue engineering scaffolds. The aim of this minireview is, besides encapsulation of the basic biochemical and biophysical properties of collagen, to summarize the most promising modern methods and technologies for production of collagen nanofibers and scaffolds for artificial tissue development.


Author(s):  
Aarti Baliga ◽  
Shashikant Borkar

In tissue engineering scaffolds take the place of the natural extra cellular matrix (ECM). The natural ECM is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The design aspect along with the choice of the material for the artificial scaffold is very crucial to cell differentiation, adhesion, proliferation, and the transport of the growth factors or other bio molecular signals. In addition to the material and design of the scaffolds, it is necessary to replicate the normal physiological situation if the scaffold has to function as an implant. The cells have to be located in the porous scaffold to form a three dimensional assembly. The article discusses the important factors to be considered while designing a scaffold for tissue engineering and regenerative medicine.


2019 ◽  
Author(s):  
R.W. Blair ◽  
N.J. Dunne ◽  
A.B. Lennon ◽  
G.H. Menary

AbstractCoronary stents for treating atherosclerosis are traditionally manufactured from metallic alloys. However, metal stents permanently reside in the body and may trigger undesirable immunological responses. Bioresorbable polymer stents can provide a temporary scaffold that resorbs once the artery heals but are mechanically inferior, requiring thicker struts for equivalent radial support, which may increase thrombosis risk. This study addresses the challenge of designing mechanically effective but sufficiently thin poly(L-lactic acid) stents through a computational approach that optimises material properties and stent geometry. Forty parametric stent designs were generated: cross-sectional area (post-dilation), foreshortening, stent-to-artery ratio and radial collapse pressure were evaluated computationally using finite element analysis. Response surface methodology was used to identify performance trade-offs by formulating relationships between design parameters and response variables. Multi-objective optimisation was used to identify suitable stent designs from approximated Pareto fronts and an optimal design is proposed that offers comparable performance to designs in clinical practice. In summary, a computational framework has been developed that has potential application in the design of high stiffness, thin strut polymeric stents that contend with the performance of their metallic counterparts.


Author(s):  
Birkan Tunç ◽  
Polat Şendur

As a result of more stringent requirements for improved fuel economy and emissions, there has been an increasing research activity to make vehicles lighter weight under some predetermined structural performance targets such as the stiffness of the vehicle body. The vehicle body structure is one of the most significant contributors to the weight of an automotive. Therefore, understanding the automotive joint properties on vehicle body performance is of significant importance as they are closely linked to structural integrity and weight of the vehicle body. In this paper, we develop a new methodology to quantify the sensitivity of critical joints of an automotive on the key performance indices. Torsional stiffness is chosen as static key performance index, while vehicle body modes are selected as dynamic key performance indices. Lower and upper sections of the A-pillar, B-pillar, C-pillar, and D-pillar of an automotive body are replaced by bushing elements having appropriate stiffness properties in the simplified model. Stiffness of bushing elements is tuned by minimizing the error between the original and simplified models on the aforementioned key performance indices. Once a satisfactory correlation is achieved between the simple model and the original model, bushing stiffness for each section is varied to determine the sensitivity of each joint. The proposed approach is demonstrated on a finite element model of 2010 Toyota Yaris. Finally, a design study is presented to improve the body key performance indices using the sensitivity results. The simulation results show that the methodology has a potential for the basic design cycle, where the targets for section properties need to be defined and at later design cycles, where the joints can be realized in design using the sensitivity of joints resulting in more efficient body structure considering the trade-offs between structural integrity and weight.


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