The biologics movement mostly started with hyaluronic acid (HA) in 1997. This natural lubricant of joints and tissues was created from chicken coxcombs. Surgeons started patients off with injections once a week for five weeks until a more crosslinked or dense version became available in the US (DUROLANE) in 2018 as a single shot. The mechanism of action was to increase lubrication in the joint, and even though the lubricant left the joint within 24 hours, patient relief often lasted up to six months. The problems were very few, except that one version (Synvisc) could cause local inflammatory reactions, but most did not.

In 1998, Dr Robert E Marx, an oral and maxillofacial surgeon at the University of Miami, released data on the use of platelets concentrated from the patient’s own blood (called PRP). Rapidly, this all-natural, from-the-patient therapy exploded, as the growth factors held within the platelets effectively improve tissue health by their anti-inflammatory and anabolic actions.

Many disciplines in medicine adopted this therapy, including plastic surgeons for facial appearances and hair loss surgeons for scalp stimulation. The problems for the scientists were that each patient had a different platelet concentration at various times of day, and each machine produced varying levels of growth factors and cells. The outcome studies were thus difficult to compare. Efforts to standardise the “dose” and the mechanism of PRP formulation mostly failed. At The Stone Research Foundation and Stone Clinic, we conducted a prospective double blind randomized study on the joint fluid before and after various injections, and concluded that one mechanism of action was the stimulation of the synovial cells lining the joint to produce a greater volume of natural hyaluronic acid. Other data indicated that recruitment factors released by the cells induced the patient’s own stem cells to migrate to the site of injury.

Since the healing actions seemed to be from “stem” cells (most accurately called mesenchymal stromal cells, or progenitor cells), these cell populations began to be harvested from bone marrow and fat and added to the lubrication and PRP injections. Patients travelled to Mexico and various other countries for treatments they believed were more potent than what was available in the US, although there was no convincing data to support that belief.

In response, and to potentially improve the outcomes, the richest source of growth factors and stem cells (made up of birth tissues of Wharton’s jelly and amniotic membranes and fluids, harvested from healthy young mothers) soon arrived on the biologic injections scene. The logic was that nothing is growing faster than the fetus, the tissues were extremely rich in all the key factors, and the tissues were discarded at the time of C-Sections of young, healthy mothers. There was strong evidence of augmented healing from these birth tissues in diabetic ulcers and burn patients when these membranes were placed on difficult-to-heal or even infected wounds. The FDA, concluding that these potent sources acted as drugs when injected, and therefore required multibillion-dollar studies to become approved, banned the use of these wound care birth tissues for arthritic joint injection. While a few companies have accepted that challenge, the use of birth tissues expanded in the US as doctors of all specialities saved their patients from the trouble of travelling overseas, improved their outcomes, and avoided the painful bone marrow and fat aspirations.

The reason why biologic joint injections are so popular is that: (1) Almost all versions of them appear to work at least to some degree, (2) They have been extremely safe despite the fact that there are limited controls and widely varied sources, and (3) there are very few complications reported. (This may in part be due to the fact that birth tissues have a natural antibiotic and immune modulatory effect, which is why the mother does not reject the fetus even though the fetus is genetically only half of the mother.)

One other mechanism of action, and possibly the most potent reason multiple forms of biologic injections work, is, as mentioned above, their ability to recruit the patients’ own stem cell reserves. Everyone, from young to old, has billions of stem cells in their body. While older people have fewer they still require billions just to stay alive every day. When a recruitment factor from PRP, birth tissues, fat, or bone is injected, it sends a siren call to those cells, and they migrate to the site of injury to direct the healing response. This is why the concentration of cells in one injection or another may not matter, nor what the source is. Our scientific and clinical interest is to find the most potent recruitment factors and optimise them for the best injection, but they all seem to work to some degree.

Once the injection is given, there is evidence that augmenting its effect with stimulation by shockwave and other energy sources, combined with immediate exercise, improves the outcomes.

A wide variety of patients we see today, those with injuries to their joints, tendons, menisci, and ligaments of the body, as well as those who suffer from arthritis, choose to try an injection of our cocktail of recruitment factors, combined with a rehab program, before they consider surgery or to make surgery more effective. So many of them do well that over half of our practice now centres around injections. It is gratifying for us to help people excel with a needle, rather than a knife.

END OF ARTICLE