TENDON AND LIGAMENT REPAIR
The incorporation of HADT tissues can decrease fibrous collagen deposition scar formation in vitro and modify inflammatory responses of tenocytes. Compared with adult wound healing, fetal wound healing has the ability to form highly aligned and organized fibers with minimal scar formation, 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-1b) compared with scaffolds without amniotic tissue. In addition, the addition of amniotic membranes also down regulated 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.
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. 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 HADT tissues and may play a role in improved soft tissue healing. 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. In flexor tendon transection models in chickens, it has been shown that the use of amniotic membranes can improve flexor tendon repair. Zone II flexor tendon injuries can lead to loss of hand functions due to the formation of fibrous adhesions and restriction of tendon gliding.
One approach to prevent tissue adhesion formation is to use membranous materials, such as amniotic membrane allografts, which can act as a barrier between the healing tendon and the surrounding tissue environment. In white leghorn chickens, digital flexor tendons were incised and repaired with a modified Kessler stitch, and amniotic membrane was sutured to the tendon proximally and distally away from the cut ends, ultimately surrounding the repaired tendon tissue. By week 12, histologic analysis revealed that tendons covered with the amniotic membrane did not exhibit granulation tissue or fibrous adhesions, as was observed with groups without amniotic membrane intervention. In addition, organized, aligned collagen fibers were observed throughout the healed tendon. Using the Tang scale to evaluate adhesion formation, it was determined that amniotic membrane coverage was beneficial in preventing adhesion when compared with repaired tendons without the graft. Collectively, these data demonstrate that the amniotic membrane can be used to assist in the treatment of reconstructed tendons and prevention of adhesions. Owing to the many growth factors contained in the HADT tissue, biomolecules such as EGF, TGF-b, FGF, and PDGF-AA and PDGF-BB may stimulate cell migration and proliferation, as well as metabolic processes such as collagen synthesis to help initiate tendon healing. In another case study, a HADT allograft patch was used to supplement a ruptured ACL that was reconstructed using a hamstring autograft.
During the arthroscopic ACL reconstruction procedure, the hamstring autograft was augmented with a HADT allograft patch fixated using the Tape Locking Screw (TLS) technique. The autografts were wrapped in HADT and rolled around 2 posts to form a 4-strand closed loop with TLS strips passed through 2 ends of the tendon loops. Subsequent magnetic resonance imaging scans revealed vascularization in the hamstring graft tissue as early as 3 months post-operative and the patient’s rehabilitation progressed successfully with regards to strength and proprioception at 8 months post-operative. Although the sample size was small for this study, this represents another example of HADT uses in clinical practices for treatment of tendon and ligament injuries. Taken together, recent preclinical and clinical findings suggest that the administration of HADT allografts is a viable option to treat tendon and ligament injuries.