Biological Therapies in Knee

Acad. Dr. en Med. Rafael Inigo Pavlovich, FACS

Orthopedic Surgeon and Sports Physician

Knee Specialist (With academic support)

Ced. Knee specialty professions State of Son. (002)

Presea “Professional Excellence” Autonomous University of Aguascalientes 2013

Biological Therapies in Knee

Throughout the evolution of species, organisms must have developed damage repair mechanisms to remain successful. Damages of various origins, from traumatic to thermal and created by Xenobiotics (external agents such as viruses, bacteria, fungi). The repair mechanism is a process where the phenomenon of inflammation is the key to the healing of a damaged tissue. Inflammation is not an increase in volume since in the common concept we say “The knee was inflamed” or “It was inflamed at the place of the blow”. The inflammation is a complex panorama of chemical reactions aimed at repairing tissues.

When there is an injury, an inflammation mechanism is awakened that calls cells of different types to work so that the tissue in question is reintegrated into its original function. For example, a skin cut will generate a biological phenomenon that leads to the expression of collagen and thus seal again this important tissue that isolates us from the outside.The repair results in a visible scar in the case of the skin, but invisible although detectable in the case of a heart muscle infarction.

Within ourselves there is the information to generate a repair and even a regeneration. The liver is a tissue that can regenerate itself, so can the bone, but not the rest of the tissues which heal and the scar is not functional, that is, the original tissue is replaced with fibrous tissue.

Biological therapies consist of using not only cells but also tissue compounds such as platelets to accelerate repair and in some cases cell regeneration, such as cartilage in orthopedics.

In biology the orders are given by the chemical compounds that react to their specific repectors and these obey by emitting the specific signal to produce collagen and other various compounds that impact the state of the cell of many tissues.

Mother cells

Stem cells are basic human cells that have the potential to give rise to different types of cells in the body. They are simple or undifferentiated cells.

 Stem cells help create new cells in healthy tissues and can help repair tissues in structures that are injured or damaged. They are the basis for the specific cell types that make up each of the organs in the body.

When stem cells divide, they create progenitor cells. Unlike stem cells, progenitor cells can develop into cells with more specialized functions, such as brain cells, red blood cells, or of particular interest to orthopedic surgeons, specialized tissue components such as bone or cartilage.

 Orthopedic surgeons have focused on mesenchymal stem cells. Unlike embryonic stem cells, these mesenchymal stem cells are obtained from living adult tissues.

 Bone marrow stromal cells are mesenchymal stem cells that, in the right environment, can differentiate into cells that are part of the musculoskeletal system. They can help form trabecular bone, tendons, articular cartilage, ligaments, and part of the bone marrow.

 At this point, stem cells in orthopedic procedures are still in an experimental phase. Most of the procedures are performed in research centers as part of controlled clinical trials.

 Stem cell procedures are used to treat bone fractures and when these fail to join, the regeneration of arthritic articular cartilage in the joints, ligaments or tendons, and the replacement of degenerative vertebral discs.

In cartilage repair, amniotic membrane has been used to fill chondral defects (cartilage defects) with promising results in experimental lambs. The amniotic membrane is a source of stem cells.

Even this is in the early stages of research and there are already some positive results out there in terms of osteoarthritis (Attrition) although nothing conclusive.

Cultured stem cells can also produce tumors if the study is not protocolized in such a way that we may not yet know how to correctly induce them to produce the adequate tissue that is needed in all cases.

There are few studies of stem cells contained in the bone marrow that relate to cartilage regeneration, however the horizon is promising.

In the studies there are those that take advantage of the stem cells that are already in the bone and are called mesenchymal cells of the bone marrow and it is in this field where there is more experience since their isolation or cuktivo is not required. cartilage injuries use a paste made in the operating room from a sample of normal cartilage that is ground and applied to the injuries. This technique that has been an aid to these types of injuries was implemented and devised by Dr. Kevin Stone from the United States and has given good results in small injuries.

Platelet rich plasma

Another biological therapy that has remained somewhat controversial is to collect by centrifugation certain compounds that are naturally in the blood and within these corpuscles there are important healing and analgesic factors.

Its main indication is in tendon pain that has not responded to treatment, although some studies try to link it with an aid for cartilage that is in the process of wear and tear.

The application of Platelet Rich Plasma to cartilage is somewhat promising during its trans-operative application, however its application to the joint can only have analgesic effects in some cases of cartilage wear or loss.

Autologous cartilage culture

This technique was approved by the FDA in 1997 and has since been marketed by Genzyme Laboratories in the United States of America under the name Carticel® (, and throughout Europe by Verigen Laboratories under the name of MACI®.

In Mexico, it was the Doctor of Medicine Eduardo Alvarez Lozano who did a doctorate in Medicine at the University of Navarra, Spain and who on his return imported the technique from Europe and set up a cell growth laboratory at the Autonomous University of Nuevo Leon in Monterrey. where you have the permission of the respective Secretary of Health

The technique is intended to repair damaged cartilage in a joint. In this technique, cartilage cells are removed from the knee and multiplied by primary culture to increase the number of chondrocytes. When enough cells are available, they are included in a three-dimensional matrix that solidifies and is subsequently reimplanted in the knee to repair the injured cartilage area and consists of two stages:

When the laboratory receives the cartilage biopsy, it is weighed, macerated, and digested using enzymes. When the chondrocytes have separated from the cartilaginous matrix, they are washed and placed in flasks containing special culture media and serum. These jars are incubated at body temperature. In the flask, a part of the cells will stick to the bottom and begin to multiply.

After three to four weeks, when a suitable cell population is obtained, they are removed from the flask through a process called trypsinization. The cells are washed again and included in a fibrin-based three-dimensional matrix, after which, when they solidify, they give rise to a bioimplant called CONDROGRAFT, which is ready for reimplantation in the patient.

The second stage involves a surgical procedure. The joint is approached through arthroscopy. The defect is identified and the lesion is cleaned, all the cartilaginous remains are extracted, the receptor bed is prepared and the bioimplant is designed in such a way that its edges contact the healthy cartilage, then the CONDROGRAFT is fixed using a “biological glue” . Finally the patient can start his rehabilitation.

This biosurgery has given great satisfaction by providing the patient with the quality of life he deserves and a greater expectation of physical activity.

Thinking that this surgery is still “Experimental” speaks of a lack of updating in the ever-changing and renewed knowledge of current medicine and the main thing would be to deny the patient an opportunity to rehabilitate his life.

The more we go into discovering the secrets of our ultra-structure, the more questions come to the fore and therefore more doubts. However, we continue in the passionate dream of research and each day someone contributes a small piece of knowledge that further enhances the great map of the human genome.Meanwhile, let’s be attentive to new discoveries and as children let’s not lose our capacity for wonder

Recommended bibliographic references for scientific consultation

Dr. in Med. Rafael Inigo Pavlovich, Dr. Javier Lozano Pardinas

Book “LIgamentous Knee Injuries” 2012

Chapter “Immunomodulation in the reconstruction of the anterior cruciate ligament, a new frontier in healing” Marge Medical Books, 2012 PP.29-44 Spanish Arthroscopy Society

Smyth NA, Murawski CD, Fortier LA, Cole BJ, Kennedy JG.

Platelet-Rich Plasma in the Pathologic Processes of Cartilage: Review of Basic Science Evidence.

Arthroscopy. 2013 May 10. 10.1016

Torrero JI, Aroles F, Ferrer D.

Treatment of knee chondropathy with platelet rich plasma. Preliminary results at 6 months of follow-up with only one injection.

J Biol Regul Homeost Agents. 2012 Apr-Jun; 26 (2 Suppl 1): 71S-78S

Gigante A, Cecconi S, Calcagno S, Busilacchi A, Enea D.

Arthrosc Tech. 2012 Sep 14; 1 (2): e175-80.

Arthroscopic knee cartilage repair with covered microfracture and bone marrow concentrate.

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