Regenerative medicine as a treatment for heel pain caused by plantar fasciosis.
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 it’s 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 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.
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 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 membranes tissues can decrease fibrous collagen deposition 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.
- Hortensius RA, Ebens JH, Harley BA. Immunomodulatory effects of amniotic membrane matrix incorporated into collagen scaffolds. J Biomed Mater Res A. 2016;104:1332–1342.
- Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol. 2007;127:514–525.
- Price RD, Myers S, Leigh IM, et al. The role of hyaluronic acid in wound healing: assessment of clinical evidence. Am J Clin Dermatol. 2005;6:383–402.
- 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.
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