Dehydrated human amniotic membrane regulates tenocyte expression and angiogenesis in vitro: Implications for a therapeutic treatment of tendinopathy

Abstract

Tendon injuries are among the most common ailments of the musculoskeletal system.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. This study evaluated the effects of micronized dehydrated human amnion/chorion membrane (μdHACM) on the inflammatory environment and hypervascularity associated with tendinopathy. Stimulation of human tenocytes with interleukin-1 beta (IL1β) induced the expression of inflammatory and catabolic markers, resulting in secretion of active MMPs and type 3 collagen that is associated with a degenerative phenotype. Treatment with μdHACM diminished the effects of IL1β, reducing the expression of inflammatory genes, proteases, and extracellular matrix components, and decreasing the presence of active MMP and type 3 collagen. Additionally, a co-culture model was developed to evaluate the effects of μdHACM on angiogenesis associated with tendinopathy. Micronized dHACM differentially regulated angiogenesis depending upon the cellular environment in which it was placed. This phenomenon can be explained in part through the detection of both angiogenic protagonists and antagonists in μdHACM. Observations from this study identify a mechanism by which μdHACM regulates inflammatory processes and angiogenesis in vitro, two key pathways implicated in tendinopathic injuries.

A decellularized flowable placental connective tissue matrix supports cellular functions of human tenocytes in vitro

“…Although excessive inflammation is thought to impair healing, recent evidence suggests that placental-derived products can interact with tenocytes and reduce the inflammatory response to support tendon healing [ 30 , 34 ]. This study sought to evaluate the effect of placental CTMs on tenocyte inflammatory gene expression (i.e., CXCL8 , TNF , TGFβ1 , TGFβ3 , and MMP1 ).…”

“…Previous research has demonstrated that the regulatory proteins contained within micronized dehydrated human amnion-chorion membrane (dHACM) reduce the expression of inflammatory genes, proteases, and ECM components, and decrease the presence of active MMPs and type III collagen [ 34 ]. The findings of the current report align with the previous report by Moreno and colleagues [ 34 ] but also suggest that the decellularization of placental tissue may promote better regulation of inflammatory processes by human tenocytes. Although decellularization is performed to reduce the host inflammatory response, it can also affect the structures and entities within the ECM, disrupting its functional characteristics [ 1 , 5 , 13 ].…”

“…Furthermore, the present report only used gene expression to evaluate tenocyte phenotype. Although gene expression has been used to evaluate tenocyte phenotype in other published reports [ 20 , 34 ], confirming gene expression with protein levels would better elucidate the biological significance of these findings. Lastly, and perhaps most importantly, this simplified in vitro study may not predict the clinical outcomes associated with the application of these CTMs.…”

Functional biomaterials for tendon/ligament repair and regeneration

“…μdHACM treatment was found to reverse the pro-inflammatory-induced increase in type 3 collagen expression and decrease the IL1β-induced type 1 and type 3 collagen levels. Researchers have also found that μdHACM can promote angiogenesis [ 99 ]. The decellularized biological scaffold can also be an effective alternative for future tendon ligament injuries after ensuring mechanical properties and avoiding rejection in vivo [ 100 ].…”

Dramatic improvement in the mechanical properties of polydopamine/polyacrylamide hydrogel mediated human amniotic membrane

“…[10][11][12][13][14] However, the mechanical properties, particularly the tensile property of the hAMs used in surgeries, are insufficient, severely restricting the promotion and application of hAMs. [15][16][17][18] Hydrogel is a material that contains a large amount of water in an internal three-dimensional network, and it has similar physical and biological properties to the extracellular matrix, making it an ideal bioadhesive material for various tissues. [19][20][21][22][23][24][25][26] Hydrogels' superior adhesion, biocompatibility, degradation, and antibacterial properties have led to rapid advancements in the eld of bioadhesion in recent years.…”