Plantar fasciitis is an inflammatory condition of the fascia. If plantar fasciitis persists, chronic inflammation can lead to long-term degenerative changes of the fascia known as plantar fasciosis. The fascia, in plantar fasciosis, can become thick and relatively hardened with loss of normal flexibility. The plantar fascia is a broad band of fascial tissue that spans the foot from the heel to the ball of the foot. It acts both to support the foot and function as a spring to aid in propulsion.
The plantar fascia, like most fascia in the body, has little or no blood supply of its own but derives that supply from surrounding muscle tissue. As the fascia thickens due to chronic inflammation, it becomes more difficult for blood to perfuse it, so the center of the fascia, the area furthest away from the blood vessels, becomes diseased.
Not all longstanding or seemingly difficult cases of heel pain are due to plantar fasciosis. The best way to determine if fasciosis is present is via imaging, specifically diagnostic ultrasound (sonography), which is the gold standard for analysis of such tissue due to its ability to show fine details.
The goal of treatment of fasciosis involves the induction or stimulation of the process of tissue repair, that is, getting the body to remove the diseased tissue and replace it with normal tissue. That is the basis of regenerative medicine.
The first form of regenerative medicine for fasciosis was ESWT, or extracorporeal shockwave therapy. ESWT involves the application of sonic shockwaves, similar to the technology used to break down kidney stones, to induce regeneration of the fascia. ESWT induces neovascularization, the production of new blood vessels, and effectively thins the fascia, making it more flexible, more functional, and less painful. The process takes approximately 12 weeks, but patients generally experience relief starting about the sixth week after treatment.
Tissue regeneration can also be encouraged by the introduction of growth factors into the fascia. Growth factors are proteins that signal tissue repair. That occurs by stimulating cell growth, cell differentiation (formation of different types of cells), and tissue repair. Tissue repair involves removal of diseased tissue and its replacement with healthy tissue. We generally explain that ESWT is a two-part process: stimulation of breakdown of bad tissue followed by creation of good tissue, although the processes can occur simultaneously. The addition of growth factors can accelerate the second half: tissue regeneration.
One of the earlier means of providing growth factors was by use of PRP or platelet-rich plasma. This involves drawing blood and removing the portion of plasma that contains platelets. Platelets are involved in the clotting mechanism but also are a source of growth factors. Stem cells are the most concentrated source of growth factors, although the process of extracting stem cells is a bit involved and expensive. Growth factors of stem cell origin can be obtained from other sources. There have been ethical questions with respect to embryonic stem cells but not so for amniotic stem cells. Amniotic stem cells are present in amniotic fluid, the umbilical cord, and amniotic membrane.
Amniotic stem cells contain naturally occurring anti-inflammatory agents such as cytokines as well as growth factors which stimulate tissue growth. Amniotic fluid is a very concentrated source of stem cells, so its use is more practical than trying to extract stem cells from a patient’s own bone marrow or fat cells. Amniotic fluid has “immune privilege,” which means that rejection of the fluid is rare. The use of amniotic stem cells is safe, effective, and well researched. The end product used has few stem cells but retains the necessary growth factors. All amniotic stem cell donors go through a rigorous screening process, as determined by the Food and Drug Administration (FDA) and American Association of Tissue Banks (AATB). Another concentrated source of growth factors comes from the umbilical cord, Wharton's Jelly. The final product used for injections has few, if any, live stem cells but contains their byproducts, the growth factors. Regenerative medicine is an effective option for treatment of plantar fasciosis. Plantar fasciosis is a degenerative condition, not an inflammatory condition. Plantar fasciitis that is left untreated or partially treated can become chronic. As the fascia continues to thicken due to chronic inflammation, blood supply to it is reduced. Fascia does not have its own blood supply but is supplied by muscles nearby. As the fascia continues to thicken, there is reduced blood supply to its central portion, which becomes scar tissue–like– stiff and painful.
We have discussed ESWT and the Topaz procedure as treatments for plantar fasciosis. Use of growth factors originating in stem cells can effectively treat plantar fasciosis. The source of the growth factors used to regenerate good fascia is donated amniotic fluid. The fluid does not have contain the actual stem cells but the substances that trigger new tissue growth. Other sources include Wharton's Jelly from the umbilical cord. Wharton's jelly may contain additional beneficial substances beyond amniotic fluid, such as hyaluronic acid.
Human amniotic membrane (HAM) consists of two conjoined layers, the amnion and chorion, and forms the innermost lining of the amniotic sac or placenta. When prepared for use as an allograft, the membrane is harvested immediately after birth, cleaned, sterilized, and either cryopreserved or dehydrated. Many products available using amnion, chorion, amniotic fluid, and umbilical cord are being studied for the treatment of a variety of conditions, including chronic full-thickness diabetic lower-extremity ulcers, venous ulcers, knee osteoarthritis, plantar fasciitis, and ophthalmic conditions. The products are formulated either as patches, which can be applied as wound covers, or as suspensions or particulates, or connective tissue extractions, which can be injected or applied topically. Fresh amniotic membrane contains collagen, fibronectin, and hyaluronic acid, along with a combination of growth factors, cytokines, and anti-inflammatory proteins such as interleukin-1 receptor antagonist. There is evidence that the tissue has anti-inflammatory, antifibroblastic, and antimicrobial properties. HAM is considered nonimmunogenic and has not been observed to cause a substantial immune response. It is believed that these properties are retained in cryopreserved HAM and dehydrated HAM products, resulting in a readily available tissue with regenerative potential. In support, one d-HAM product has been shown to elute growth factors into saline and stimulate the migration of mesenchymal stem cells both in vitro and in vivo.
HAM is an established treatment for corneal reconstruction and is being evaluated for the treatment of various conditions, including skin wounds, burns, leg ulcers, and prevention of tissue adhesion in surgical procedures. Additional indications studied in preclinical models include tendonitis, tendon repair, and nerve repair. The availability of HAM opens the possibility of regenerative medicine for a wide variety of conditions.
The incorporation of amniotic membrane tissues can decrease fibrous collagen deposition and scar formation in vitro and modify inflammatory responses of tenocytes.52 Compared with adult wound healing, fetal wound healing has the ability to form highly aligned and organized fibers with minimal scar formation,53 suggesting that fetal tissues and the fetal environment may be uniquely capable of supporting tissue regeneration. Therefore, one approach to recapitulate fetal healing is to use ECM-based biomaterials that originate from environments with anti-inflammatory and antimicrobial properties, such as amniotic tissue. It was shown that when amniotic membrane tissue was incorporated into tenocyte-laden collagen-glycosaminoglycan scaffolds, cells exhibited increased metabolic activity in both basal and proinflammatory environments (induction with IL-1β) compared with scaffolds without amniotic tissue.52 In addition, the addition of amniotic membranes also downregulated the gene expression of the proinflammatory molecules tumor necrosis factor-α and matrix metalloproteinase-3 in tenocytes, indicating that this biomaterial could alter the inflammatory response associated with scar formation in tendon healing to better mimic fetal soft tissue healing.52 Methods of incorporating hyaluronic acid (HA) have also been explored to reduce scar formation, as HA is known to play a role in chronic wound healing by promoting cell proliferation and motility.54,55 As a critical component of several orthopedic tissues including cartilage and synovial fluid, HA contributes both mechanical properties as well as the ability to regulate cellular activity through interaction with growth factors and binding of cell surface receptors, such as CD44. In particular, HA is an ECM component that has been detected and quantified in dHACM tissues and may play a role in improved soft tissue healing.56 Thus, the use of amniotic membranes that contain HA could potentially be an effective method to help modulate the inflammatory environment to decrease scar formation during tendon and ligament healing.
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Liu Y, Skardal A, Shu XZ, et al. Prevention of peritendinous adhesions using a hyaluronan-derived hydrogel film following partial-thickness flexor tendon injury. J Orthop Res. 2008;26:562–569.
Lei J, Priddy LB, Lim JJ, et al. Identification of ECM components and biological factors in micronized dehydrated human amnion/chorion membrane. Adv Wound Care. 2016;6:43–53. In press.
For treatment of plantar fasciitis, a prospective, randomized, blinded clinical trial with 45 patients revealed that micronized dHACM administration is a viable treatment option to decrease pain. Micronized dHACM was first reconstituted in 0.9% saline at 0.5 or 1.25 cc. For administration of either the dHACM treatment or saline control, patients received a 2 cc injection of Marcaine to the medial origin of the plantar fascia, followed by an injection of 0.9% saline control or 0.9% saline containing the reconstituted micronized dHACM.
Zelen CM, Poka A, Andrews J. Prospective, randomized, blinded, comparative study of injectable micronized dehydrated amniotic/chorionic membrane allograft for plantar fasciitis—a feasibility study. Foot Ankle Int. 2013;34:1332–1339.
