Why Does Amniotic Membrane Ease Tendinopathic Pain?

Two new studies, sponsored by MiMedx Group, Inc., have found intriguing evidence which may explain the ability of human amniotic membrane to reduce inflammation and pain associated with tendinopathy.

According to the research teams behind these studies, two painful processes lie at the heart of tendinopathy—prolonged inflammation and persistent vasculature.

Persistent vasculature refers to a process when vascular structures either fail to wither, or regress, or grow to a pathological extent. This can occur in fetuses and when it does, it is most commonly referred to as persistent hyperplastic primary vitreous (PHPV).

One of the key functions of amniotic tissues in-utero is to prevent persistent vasculature syndrome. Hypervascularity is also a hallmark of chronic tendinopathy. The second of these two new studies found fascinating evidence that dehydrated amniotic membrane was able to interrupt this hypervascularity.

The first study, “Human amniotic membrane modulates Wnt/β-catenin and NF-_Kβ signaling pathways in articular chondrocytes in vitro” published in the December 2021 issue of Osteoarthritis and Cartilage Open, evaluated dehydrated human amniotic membrane as a treatment option for osteoarthritis.

For the study, 3-D human articular chondrocyte pellets were stimulated with an inflammatory cocktail and then treated with varying doses of dehydrated human amniotic membrane.

The researchers found that dehydrated human amniotic membrane (supplier MiMedx Group) regulates the degradative processes in human articular chondrocytes. The research group concluded that dehydrated human amniotic membrane is a promising investigational new drug for osteoarthritis and should be studied further.

The second study, “Dehydrated human amniotic membrane regulates tenocyte expression and angiogenesis in vitro: Implications for a therapeutic treatment of tendinopathy,” modeled tendinopathy in vitro to evaluate dehydrated human amniotic membrane as a treatment option.

“Prolonged inflammation and persistent vasculature are common complications associated with poor healing. Damaged tendon, replaced with scar tissue, never completely regains the native structural or biomechanical properties,” the researchers wrote.

The findings were published on October 5, 2021, in the Journal of Biomedical Materials Research.

For this study, the researchers first stimulated human tenocytes with interleukin-1 beta to induce tendinopathy. Then they introduced dehydrated human amniotic membrane to evaluate its role in regulating the inflammatory environment and matrix degradation.

They found it diminished the effects of the interleukin-1 beta, including the downregulation of IL^, MCP1, MMP1 and MMP3. It also reversed the proinflammatory-induced expression of type III collagen which indicated an immature matrix formation and weakened mechanical properties in tendon tissue.

“Regulation of extracellular matrix components alludes to a potential role for dehydrated human amniotic membrane in the direct repair of the damaged tissue,” the researchers wrote.

Next, they tested the effects of dehydrated human amniotic membrane on vessel formation. For this, human endothelial cells were grown on top of a single layer of human tenocytes. It turns out that it also promotes angiogenesis which was evident by the organization of vascular networks. However, when dehydrated human amniotic membrane is introduced in a culture with an already established network, it tended to disrupt the network.

“This dynamic response is the first documentation of dehydrated human amniotic membrane stimulating differential outcomes based upon the environment in which it is placed. Hypervascularity is a hallmark of chronic tendinopathy; therefore, these results suggest dehydrated human amniotic membrane treatment may function to reduce the presence of abnormal vessels within the tendon and ultimately repair the damaged tissue,” they wrote.

“These studies reaffirm our commitment to advancing the science of amniotic tissue,” Timothy R. Wright, chief executive officer of MIMEDX, said in a statement.

“Through our continued investment in research and clinical development, we aim to demonstrate the utility of PURION Processed mdHACM as a platform for regenerative medicine. With each new study, we broaden our understanding of the product’s mechanism of action and further our potential for applying these scientific findings to advance meaningful medicines in areas of unmet clinical need.”