Dual growth factor‐immobilized asymmetrically porous membrane for bone‐to‐tendon interface regeneration on rat patellar tendon avulsion model

Abstract

Insufficient repair of the bone-to-tendon interface (BTI) with structural/compositional gradients has been a significant challenge in orthopedics. In this study, dual growth factor (platelet-derived growth factor-BB [PDGF-BB] and bone morphogenetic protein-2 [BMP-2])-immobilized polycaprolactone (PCL)/Pluronic F127 asymmetrically porous membrane was fabricated to estimate its feasibility as a potential strategy for effective regeneration of BTI injury. The growth factors immobilized (via heparin-intermediated interactions) on the membrane were continuously released for up to 80% of the initial loading amount after 5 weeks without a significant initial burst. From the in vivo animal study using a rat patellar tendon avulsion model, it was observed that the PDGF-BB/BMP-2-immobilized membrane accelerates the regeneration of the BTI injury, probably because of the continuous release of both growth factors (biological stimuli) and their complementary effect to create a multiphasic structure (bone, fibrocartilage, and tendon) like a native structure, as well as the role of the asymmetrically porous membrane as a physical barrier (nanopore side; prevention of fibrous tissue invasion into the defect site) and scaffold (micropore side; guidance for tissue regeneration).

Biomimetic strategies for tendon/ligament-to-bone interface regeneration

“…However, single factor can not fully mimic the complex process of physiological events during the interface healing. To enhance the regeneration of tissues with heterogeneous cell types and matrix compositions, delivering multiple bioactive growth factors into the target region is essential [ 96 ]. For example, Kim et al fabricated platelet-derived growth factor-BB (PDGF-BB)/bone morphogenetic protein-2 (BMP-2)-immobilized membrane to facilitate interface healing in a rat patellar tendon avulsion model [ 96 ].…”

“…To enhance the regeneration of tissues with heterogeneous cell types and matrix compositions, delivering multiple bioactive growth factors into the target region is essential [ 96 ]. For example, Kim et al fabricated platelet-derived growth factor-BB (PDGF-BB)/bone morphogenetic protein-2 (BMP-2)-immobilized membrane to facilitate interface healing in a rat patellar tendon avulsion model [ 96 ]. The results demonstrated that delivery of single growth factor might be insufficient to reconstruct the tendon-to-bone interface with a multiphasic structure, whereas the delivery of both PDGF-BB and BMP-2 may provide a synergistic effect to generate a multiphasic structure similar to the native enthesis structure.…”

Impact of PDGF‐BB on cellular distribution and extracellular matrix in the healing rabbit Achilles tendon three weeks post‐operation

“…It is well known that PDGF-BB enhances proliferation of fibroblasts [17][18][19]. In addition, PDGF-BB acts via chemotaxis and has an influence on the cell migration.…”

PDGF Enzymatic Activity in Patients With Delayed Fracture Consolidation

“…Bayer с соавторами рассматривают различные варианты доставки микросферами фактора роста и морфогенетического белка [4]. следует отметить, что применение pdgF в трав-матологической практике является перспектив-ным направлением, и в настоящее время в мире идет активный поиск способов доставки, сро-ков и длительности эффективного применения pdgF для ускорения костной регенерации [3][4][5]. недавно корейскими учеными было доказано ускорение регенерации при использовании мик-росфер с ассиметричными порами в мембранах, которые высвобождали pdgF-ВВ и ВМР-2 [5].…”

“…следует отметить, что применение pdgF в трав-матологической практике является перспектив-ным направлением, и в настоящее время в мире идет активный поиск способов доставки, сро-ков и длительности эффективного применения pdgF для ускорения костной регенерации [3][4][5]. недавно корейскими учеными было доказано ускорение регенерации при использовании мик-росфер с ассиметричными порами в мембранах, которые высвобождали pdgF-ВВ и ВМР-2 [5]. по данным других авторов, проводивших исследова-ние на животных, использование тромбоцитар-ного и эндотелиального (VegF) факторов роста сосудов в комбинации с ВМР-2 более эффективно для костной регенерации по сравнению с моноте-рапией ВМР-2 [6].…”