Scaffolds in tissue engineering bone and cartilage
Dietmar W. Hutmacher, Scaffolds in tissue engineering bone and cartilage, Biomaterials, Volume 21, Issue 24, 15 December 2000, Pages 2529
Summary: This paper introduces the research on the scaffolds in tissue engineering of bone and cartilage. The material used for scaffold, design characteristics, as well as the fabrication technologies are described and evaluated in the paper.
There are six phases in tissue engineering program for bone and cartilage: the fabrication of scaffold (I), seeding of stem cells into scaffold in vitro (II), growth of premature tissue in dynamic environment (III), growth of mature tissue in bioreactor (IV), surgical transplantation (V) and transplant remodeling (VI). The first phase, the design and fabrication of a porous 3D scaffold is emphasized in this paper. The material used for scaffold should be highly biocompatible, and it can degrade and resorb at a same controlled rate as the seeded tissue cells proliferate and excrete their own ECM. Several scaffold materials, including hydroxyapatite (HA), poly(α-hydroxyesters), and natural polymers such as collagen and chitin, are investigated. The materials are selected based on their ability to withstand mechanical loading in vitro and in vivo, and their intrinsic mechanical property to template the cell proliferation and differentiation to phase IV.
In order to achieve significant strength, a physical and chemical structure allowing for hydrolytic attack and breakdown is very essential. In the scaffold design, concept of tensegrity is applied to make the entire scaffold structure evenly distributes and balances mechanical stresses. Also the diffusion of nutrients in to 3D scaffold is another consideration to ensure the survival and function of seeded cells.
Currently, there is a number of fabrication technologies applied to process material into 3D scaffolds. In this paper, key characteristics and parameters of each technique are summarized and compared, and advantages and disadvantages of techniques are further studied. At the end of the paper, the example of tissue engineering of an articular cartilage-bone interface is introduced under the concepts discussed above.
Significance: Nowadays, bone and cartilage generation by autogenous cell or tissue transplantation is considered to be one of the most promising techniques in tissue engineering. The 3D scaffold can provide the necessary support for seeded cells to proliferate and maintain their differentiated function, it can also define the various shapes of the new bone and cartilage. Selection of materials and design concepts could eliminate problems of donor site scarcity, immune rejection and pathogen transfer. The summarization of current scaffold fabrication technologies provides research teams comprehensive information to assist them with their choice for a specific method under different criteria.
Summary: This paper introduces the research on the scaffolds in tissue engineering of bone and cartilage. The material used for scaffold, design characteristics, as well as the fabrication technologies are described and evaluated in the paper.
There are six phases in tissue engineering program for bone and cartilage: the fabrication of scaffold (I), seeding of stem cells into scaffold in vitro (II), growth of premature tissue in dynamic environment (III), growth of mature tissue in bioreactor (IV), surgical transplantation (V) and transplant remodeling (VI). The first phase, the design and fabrication of a porous 3D scaffold is emphasized in this paper. The material used for scaffold should be highly biocompatible, and it can degrade and resorb at a same controlled rate as the seeded tissue cells proliferate and excrete their own ECM. Several scaffold materials, including hydroxyapatite (HA), poly(α-hydroxyesters), and natural polymers such as collagen and chitin, are investigated. The materials are selected based on their ability to withstand mechanical loading in vitro and in vivo, and their intrinsic mechanical property to template the cell proliferation and differentiation to phase IV.
In order to achieve significant strength, a physical and chemical structure allowing for hydrolytic attack and breakdown is very essential. In the scaffold design, concept of tensegrity is applied to make the entire scaffold structure evenly distributes and balances mechanical stresses. Also the diffusion of nutrients in to 3D scaffold is another consideration to ensure the survival and function of seeded cells.
Currently, there is a number of fabrication technologies applied to process material into 3D scaffolds. In this paper, key characteristics and parameters of each technique are summarized and compared, and advantages and disadvantages of techniques are further studied. At the end of the paper, the example of tissue engineering of an articular cartilage-bone interface is introduced under the concepts discussed above.
Significance: Nowadays, bone and cartilage generation by autogenous cell or tissue transplantation is considered to be one of the most promising techniques in tissue engineering. The 3D scaffold can provide the necessary support for seeded cells to proliferate and maintain their differentiated function, it can also define the various shapes of the new bone and cartilage. Selection of materials and design concepts could eliminate problems of donor site scarcity, immune rejection and pathogen transfer. The summarization of current scaffold fabrication technologies provides research teams comprehensive information to assist them with their choice for a specific method under different criteria.
12 comments:
This research is especially appropriate considering how prevalent cartilage (e.g. meniscus and ACL) and bone degeneration are in our population of young and old athletes. As athletes push themselves to extreme degrees and continue to exercise at later ages, they risk more severe injuries including degenerative long-term ones. The idea that we can engineer scaffolds to be seeded with autogenous cells to replace damaged tissue is encouraging because it begins to address the problems of biocompatibility in synthetic biomaterials. The paper I summarized utilized similar methods for engineering pulmonary heart valves, however a key difference is that they used biological scaffolds derived from the patients own body or from a donor. I wonder if it may be possible to transition to using biological scaffolds in this case as well to escape the issues of inflammation and immune response that challenge biocompatibility?
I know very little about bio-materials and tissue engineering scaffolds, but I was wondering if you knew how they worked. Do the scaffold materials simply degenerate over time once they are implanted? Or are the scaffolds responsive to the ECM created by the cells seeded within them? What are the by-products of scaffold degeneration? Are the materials completely metabolized by cells? Are any of the by-products mildly toxic? It seems like rigorous testing of many biomaterials have been done, but are there many studies about the long term effects of using these scaffolds for tissue regeneration? The paper seems to imply that it worked well initially, but it would be interesting to know about its long term effects.
Joy:
Actually they do make the scaffold into biological scaffolds by seeding the stem cells from patient or donor (same as your case) into scaffold. The materials I talked about are only for fabricating the scaffold structure, which will degrade later to allow seeded cells to proliferate.
Jennifer:
I think the degradation of scaffold material is controlled by researchers since it has to be maintained at same rate as seeded cell grow. The degradation might be affected by seeded cells if the scaffold material is biological, like collagen.
Could you comment on the relative efficiency and safety of the various materials mentioned in the paper? For instance, the paper mentioned that poly(alpha-hydroxy acids) can undergo a degradation phenomenon in which degraded polymers are trapped, leading to catastrophic release of acidic components later. On the other hand, it is still used as material to scaffold.
I am also interested in your thoughts regarding the 2 strategies described for integrating scaffold, replacement tissue (bone/cartilage), and the host tissue. Strategy I appears to focus improving strength at the cost of compatibility whereas strategy II appears to be the reverse.
Lastly, can you explain how tensegrity works? How does it distribute mechanical forces? How does this work in the biological environment, where cells in different regions could be applying greatly varied loads on the framework?
Spectator:
Concept of tensegrity: Geodesical 3-D constructs were designed by applying tensegrity so that the entire scaffold structure evenly distributes and balances mechanical stresses. The walls, layers or struts that make up the interconnecting scaffold framework are connected into triangles, pentagons or hexagons, each of which can bear tension or compression.
You discuss in your paper different kinds of scaffolds that can be used and biocompatibility plays a big role in what material scaffolds are made of. Besides anticoagulants, what other chemical interventions can be used to allow a scaffold to be minimally detected by the immune system? Furthermore, for most implants into the body, protein adsorption is preferably kept to a minimum, in order to evade the immune system response. Do you think that protein adsorption is a big factor with these scaffolds?
Atul:
The scaffold is actually made by the tissue(cells) from the patient, therefore, immune response should not be a big issue. Also I don't think protein absorption is an big factor in this case.
You mentioned that scaffolds are generated using a time of fabrication techniques, and it got me really interested. Are these techniques feasible for large scale production of scaffolds or is it more a research level technology? What are some of the rate-limiting steps in some of the techniques used. Are there ways to make them more efficient?
Aron:
I believe this technology is more research level. The rate limiting steps include degradation rate, resorption rate, proliferation rate.
Hi Ye,
You have discussed the many different scaffold materials which are being explored in current research; does the paper mention the relative efficiency of these materials? Also you stated that the materials are tested in vitro and iv vivo for their abilities to withstand mechanical loading but are there any specific techniques discussed on how this is accomplished in vivo?
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