Peptides for joint repair – The use of cells to repair and replace damaged tissues or organs is an emerging field in reparative medicine. Until recently, this discipline was for repairing and restoring lost function due to disease, damage or loss of body parts and may or may not involve an in vitro component.
The material used as a substitute (vascular, abdominal, or bone prostheses) was implanted in the patient and had to integrate with the recipient’s tissue. The responses that this entails are foreign body, immunological and antigenic recognition.
The remodeling phenomenon improves the structure and function of the damaged or lost organ and tissue. It depends on a wide variety of factors; including the composition of the implanted material, the presence of a cellular component and processing methods.
Peptides for Tendon Repair
Today, reparative medicine encompasses many other disciplines: cellular and molecular biology, surgery, engineering, and chemistry, among others. The conjunction of all these fields makes it possible for the so-called living tissue engineering to emerge. It is a science that began from 2 perspectives: cell therapy and the science of biomaterials.
The union of these two aspects makes possible the design and, later, the construction of substitutes (constructs). It can repair, regenerate, functionally, and structurally replace tissue organs of patients that have lost their full functionality or been mechanically damaged or physiologically. Thus, the research controls the design of the material to its implantation and correct functioning in the recipient individual.
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Normal tissue is from structural and cellular components. For it to carry out its function, both components are interrelated so that one supports the other. There is a vascular network responsible for transporting different external signals (cytokines, growth factors, hormones, etc.) to the cells. These nourish and oxygenate the cells and, simultaneously, eliminating cellular waste. It is the basic model tissue engineering must build to achieve substitutes for clinical use.
Biomedical engineers have begun to develop specific techniques for synthesizing functional tissues. The great barrier to overcome is in transferring the experimental results to the large-scale production of these constructs with appropriate materials in the field of reparative medicine. The last point implies delving into the necessary methodology. It allows, on the one hand, to maintain the viable cell population in the biomaterial and, on the other, to induce its proliferation and differentiation in the appropriate environment.
For this, bioreactors have instruments capable of inducing histogenesis under certain conditions. Its large-scale use and promising results could produce three-dimensional tissues and composite tissues for repairing and regenerating damaged organs and tissues in reparative medicine.
Currently, tissue engineering is a reality in animal experimentation, with little success in human clinical practice. The results are encouraging, although it is necessary to delve into the mechanisms of tissue construction to achieve structurally and functionally replicas that can replace non-functional organs and tissues.
Peptides for Joint Repair
Cell therapy is the field with the most significant objective perspective in human clinical practice. This science is based on the therapeutic use of cellular products, among which the transfer of cells or tissues, autologous or heterologous, to damaged tissues or organs stands out. The best-known cell therapy is bone marrow transplantation to treat hematological tumors and some solid tumors.
Although the use of myoblasts in myocardial repair, the treatment of dermal ulcers and extensive burns with skin grown in vitro, the treatment of corneal ulcers and alterations of the corneal membrane with amniotic membrane, immunotherapy and, recently, the treatment of fistulas in Crohn’s disease through the use of stem cells from subdermal fat.
Currently, local defects affecting the articular cartilage of the knee are successfully repaired in clinical medicine.
Cell Therapy and Cartilage
Lesions that affect cartilage, such as osteoarthritis, entail alterations in the characteristics of the cellular and structural components. The symptomatology depends on the magnitude and location of the injury. With traditional therapeutic methods (therapeutic gymnastics and taking anti-inflammatory drugs), symptoms generally improve. In the advanced stages of articular cartilage destruction, we speak of osteoarthritis. The entire joint is swollen and cannot be fully flexed or straightened. Resting pain also occurs at this stage. The therapeutic concept depends on the magnitude and location of the cartilage lesions. In any case, we face emerging diseases and will also see more frequently every day in consultations and hospitals.
Two hundred fifty years ago, Hunter was the first to describe that damaged articular cartilage was not capable of repairing itself. Cartilage is an avascular tissue, which directly implies the normal inflammatory response.
With hemorrhage, fibrin plug formation, cellular protein synthesis and mesenchymal cell migration are absent, limiting usual self-repair processes. The factors that influence the repair process are the injury’s age, depth and damage, whether traumatic, chronic or associated with instability, a previous meniscectomy or genetic predisposition.
Peptides for Cartilage Repair
Age is a crucial factor to consider, given that the number of mesenchymal cells with the capacity to regenerate tissues decreases with age. Thus we find one in every 10,000 cells in newborns, one in every 400,000 in individuals aged 50 and, one in 2,000,000 in octogenarians. The depth of the injury also affects the repair process, superficial wounds do not penetrate the chondral surface, and there is no blood supply (inflammatory cells and fibroblasts generate a new matrix, even if it is not ideal).
Injuries from trauma will repair better than areas with degenerative defects. Structural instability and other associated pathologies are often related to irregular forces on the joint surfaces.
Current treatments such as microfracture allow the exit of stem cells to the area of injury, abrasion (to create new cartilage ) or debridement.
These techniques facilitate repair by improving chondral function and symptomatology. It also favors the formation of fibrocartilage instead of regular, hyaline cartilage.
Fibrocartilage seems to be deposited by fibroblasts that reach the area of injury via the bloodstream after the surgical procedure.
Other treatments such as:
-autografts (limited by the viability of the patient’s tissue)
-osteochondral allografts, which tend to degenerate over time
-autologous transplantation of chondrocytes or chondrogenic progenitors
Whether in polymers or hydrogels, they have shown promising results in reducing pain and joint cartilage dysfunction.
Autologous chondrocyte implantation is today a reality as cell therapy in treating focal cartilage defects in the femoral condyles of the knees. We can find a wide range of products for medical use. Many are in the clinical trial phase, whose therapeutic basis is the implantation of autologous chondrocytes, alone or accompanied by different matrices.
However, this technique currently has some drawbacks: the age of the patients is critical, given that they cannot exceed 55 years.
The process requires two surgical interventions (obtaining cartilage and implanting chondrocytes). The seeding and culture of autologous chondrocytes is a long process (3-4 weeks). Patients with primary cartilage defects cannot be included in the autologous implantation program, since they lack competent cells.
These limitations can be overcome through the use of an alternative cell source. Model cells from umbilical cords can be frozen and stored. It is a methodology that may provide new clinical applications in human cell therapy.
The current challenge lies in the formation of complex cartilaginous structures. Experimentally, there are groups that, using molds in bioreactors, have synthesized human ears, nasoseptal implants and temporomandibular discs
Within the field of knee femoral condyle repair, basic research is focusing its efforts on several avenues:
What is the Best Peptide for Healing?
To do this, they use polymers of lactic acid, hydroxy acids or copolymers of lactic and glycolic acids to support cell growth. The disadvantage of these polymers is that there is a loss of cell attachment over time. To solve this problem, there are already groups working on RGD16 peptides that, together with the polymers, would favor cell adhesion, improving the quality of the construct.
- Use of growth factors (TGF-ß) to improve both the quality and the time of the repair.
- Synthesis of neocartilage on cultured bone as support and, once grown, implant it in the injured area.
The indicated therapeutic alternatives, also called “bio-prostheses”, could regenerate the worn or missing cartilage coverage only if collateral damage, such as meniscal tears, joint instability or erroneous axial positions, are simultaneously eliminated. We see then that therapeutic variability is considerable and is not always the most appropriate. In the future, other treatments based fundamentally on undifferentiated cells, such as adult stem cells, will have an important field of application for these processes, as will some gene therapies.