Article Authors: Gordon Slater|Tandose Sambo
Introduction
Tissue Engineering (TE) is a medical innovation that is revolutionizing how orthopaedic treatments are administered. They optimize current orthopaedic treatments for injuries such as sports related injuries, and increase the patient performance and recovery time. As a combination of therapies, the activities all work synergistically in order to restore the body’s healing. As TE applications become more prevalent, it is useful to understand their benefits.
An orthopaedic injury, like all injuries, is a cause of concern to the patient from various perspectives. Injured patients are faced with both physical and mental stresses after their condition develops. First, there’s the inconvenience of potential immobility, coupled with the economic stress of having to pay for healing and recovery. Some orthopaedic conditions require the utilization of surgical procedures in order to restore the patient to optimal health. Recovery from a surgical procedure can be extensive and take up to a few months in some instances.
One of the functions of orthopaedic surgery is the utilisation of intervention methods that aim to restore the mechanical integrity of the body. With time, there are some aspects of the body’s healing mechanisms that deteriorate, and the healing of tissues such as cartilage and ligaments takes a longer time to achieve. Some bone and tissue functions that do have the ability to restore, do not do this to the original capacity.
The healing of orthopaedic tissues is found to be directly correlated to the incorporation of four main elements: cells, morphogenetic signals, scaffolds and mediums that will support the mechanical structure of the body. Bioengineering procedures have enabled the development of tissue regenerative materials that will restore both the mechanical integrity of bone, and also facilitate the restoration of the ligaments, cartilage and even blood vessels that are associated with particular regions of the body such as the ankles and the knees. Based on this fact, body parts can be regenerated and restored.
Via medical research, source tissues for tissue engineering are collected from various bodily sources and the importance of each of the differing cell sources is yet to be identified. In the medical realm:
- Stem cell research is understudy to identify the most effective cells to introduce to specific healing sites.
- For morphogenetic signals their influence by growth factors or other sources such as platelet rich plasma is currently being elucidated
- Smart scaffolds that integrate with the body are also under investigation
As medical knowledge on a topic expands, it will be possible to overcome the obstacles to the current incorporation of engineered tissue into the orthopaedic treatment plan. In the future, as synthetic and biologic material properties are better understood it will be possible to combine all of these elements in order to apply them to therapies. Industry best practices and federal approvals still have to be established before the full implementation can be accepted globally.
Regenerative Treatments
The human body is designed to heal itself. Medical science utilises knowledge of these healing mechanisms to enhance the restoration of health when there is an onset of an illness. The body’s skeleton is one prime example of a mechanism that has to heal itself in situ. Bone cells regenerate spontaneously, and new cells are always being regenerated, to replace the ones that have been absorbed by the body. One of the beautiful things about bone is that in its natural state, bone will heal without scarring.
When excessive stresses are introduced to the body, with enough lateral forces to a bone, it will be possible to shear or break the bone in such a way that the bone will have to have external intervention for healing and restoration. Some aspects of the body do not have the ability to heal after injury. Changes in orthopaedic surgery that are dedicated to the restoration of bone include the development of bone morphogenetic proteins that catalyse healing processes of the bone.
How Bones Heal
The body has built in healing mechanisms that are able to facilitate the restoration of bone once there’s a fracture. The healing of bones is a long process and can take up to twelve weeks. The healing process takes place in a series of sequential mechanisms.
Stages of Indirect Healing
Acute Inflammatory Response
The human body is a very smart mechanism, and the healing process begins almost immediately after the fracture has occurred. The body usually instantaneously senses that there’s an injury. The body may initially go into shock to numb the pain of the trauma, and then start the process of healing the wounded site. Inflammation is the first step of the bone healing process. The acute inflammatory response is an activity that takes place within 24 hours of the fracture, and lasts for approximately seven days subsequent to the fracture.
The healing process is initiated by the formation of a haematoma. The body is nourished by the blood, and the bones do have a blood supply. Once there is a fracture, blood will rush to the site and accumulate around the fractured site. The concentrated blood will then start to clot, and with the constituents of peripheral and intramedullary cells and bone marrow cells. This framework will cause the formation of a callus.
Recruitment of Mesenchymal Stem Cells
The stem cell has long been identified as the regenerative life force in our bodies. With their ability to divide and duplicate, as well as generate new and different stem cells that are relevant to a healing site, it is possible to regenerate cartilage cells and even bone cells. This is great news for the broken bone. With the ability to rebuild the bone naturally, having an abundance of these cells will save the individual time during the healing processes.
Stem cell therapy as a regenerative medicine, is also emerging as a means to heal the body. The stem cells are those parts of our bodies that are able to create new cells as needed by the body. With time, our stem cell count diminishes. Via external injections however, healing can be restored to a site. In the regenerative realm, researchers are studying how stem cells can be used to replace, repair, reprogram and even renew diseased cells. When healthy cells abound, the appropriate mechanisms of healing will follow.
As undifferentiated, yet intelligent cells, stem cells have the amazing ability to grow and develop into the cells the body needs for a healing mechanism. The sources of these stem cells vary from sites such as a placenta (embryonic stem cells), garnered from a labor and delivery exercise, to adult stem cells that are extracted from places like the fat of the body, and genetically reprogrammed to the desired purpose. The latter stem cells are known as induced pluripotent stem cells. The current medical studies are aiming to identify how reprogrammed stem cells specifically generate specialized stem cells that are able to repair cells in healing sites such as the heart, foot and ankle and also in the nervous system. Bone is unable to regenerate unless specific mesenchymal stem cells are recruited, proliferated and differentiated into osteogenic cells.
Fibrin-rich granulation tissue forms after the haematoma has developed. Efforts to stabilize the site are facilitated by the formation of endochrondals. Soft callus formation takes place by the 7 day stage of healing. A hard callus starts to form in parallel with the soft callus. The hard callus will eventually enable the bone to bear weight at the appropriate time.
Revascularization and Neoangiogenesis
Within the bone, there is a blood supply that enables the bones to stay healthy and regenerate. The blood is the source of all healing mechanisms, and it will be critical for bone repair. Via the appropriate mechanisms, blood vessels are directed to the healing site, to ensure that healing cells have access to the repair.
Mineralization and Resorption of the Cartilaginous Callus
During the healing process, the soft callus is resorbed in the body, and the hard callus remains as the permanent structural support of the bone. Via the mechanism of embryological bone development and involvement of the processes of cellular proliferation and differentiation, an increase in cellular volume and matrix deposition, the bone integrity is restored.
Bone Remodeling
With the restorative process, there is a second restorative stage after the development of the hard callus. The hard callus is subsequently remodelled, in order to generate a lamellar bone structure that contains what is classified as a central medullary cavity. Just as the soft callus is resorbed and replaced by the hard callus, the hard callus is resorbed by the body and replaced by the lamellar bone created by system osteoblasts. As a sequential process, the establishment of lamellar bone structure takes place at the 3-4 week mark.
How Long Does Bone Healing Take?
Bone healing takes approximately six to twelve weeks, in order to achieve a desired outcome. Healing in children is often faster in children than in adults. Via consultations, the foot and ankle surgeon will be able to determine if the patient is able to bear weight on the bone.
Regeneration of the Skeletal System
Within the skeletal system, as outlined above it is important for the various elements to be incorporated into the healing mechanism in order for it to be effective. The skeleton bears mechanical loads and it moves with mechanical stimuli. Tissue engineering technologies have been incorporated that will enable the restoration of the relevant tissues that will keep the bone function at peak. The generation of these tissues involves the utilization of patient autologous cells, growing them in a culture, and then seeding them onto a scaffold. Bioreactors are the incubators of our cell cultures. Success of this method is a promising technique that will lead to proliferation of regenerative methods in orthopaedic care.
As the ideal methods for culturing cells is under debate, the truth of the application cannot be overseen. Practicality will result in an initial focus on minimally invasive procedures that will incorporate these engineered tissues. With time, and better understanding, more sophisticated applications can be identified.
Article References
[1] Mayo Clinic: https://www.mayoclinicproceedings.org/article/S0025-6196(13)00477-1/pdf