Tissue Engineering of Large Full-Size Meniscus Defects by a Polyurethane Scaffold: Accelerated Regeneration by Mesenchymal Stromal Cells

Abstract

The endogenous healing potential of avascular meniscal lesions is poor. Up to now, partial meniscectomy is still the treatment of choice for meniscal lesions within the avascular area. However, the large loss of meniscus substance predisposes the knee for osteoarthritic changes. Tissue engineering techniques for the replacement of such lesions could be a promising alternative treatment option. Thus, a polyurethane scaffold, which is already in clinical use, loaded with mesenchymal stromal cells, was analyzed for the repair of critical meniscus defects in the avascular zone. Large, approximately 7 mm broad meniscus lesions affecting both the avascular and vascular area of the lateral rabbit meniscus were treated with polyurethane scaffolds either loaded or unloaded with mesenchymal stromal cells. Menisci were harvested at 6 and 12 weeks after initial surgery. Both cell-free and cell-loaded approaches led to well-integrated and stable meniscus-like repair tissue. However, an accelerated healing was achieved by the application of mesenchymal stromal cells. Dense vascularization was detected throughout the repair tissue of both treatment groups. Overall, the polyurethane scaffold seems to promote the vessel ingrowth. The application of mesenchymal stromal cells has the potential to speed up the healing process.

Meniscus Regeneration Strategies

“…The first 12-month report showed tissue ingrowth into the scaffold at this time and consistent MRI and histology data (Verdonk et al 2011). In an animal model, this biomaterial showed an accelerated in growth in the surrounding native cartilage when seeded with mesenchymal stem cells (Koch et al 2018). However, at the moment this biomaterial is not available for clinical use.…”

“…Due to their potential for differentiation, trophic modulation, and good availability, MSCs appear to be the best cell source to support meniscal healing (Zellner et al 2017). In different animal models, MSCs showed promising results regarding the development of differentiated meniscus-like repair tissue in small or large meniscus defects or meniscus tears, even in the avascular zone (Angele et al 2008;Zellner et al 2010Zellner et al , 2013Koch et al 2018). Vangsness et al injected allogenic MSCs for meniscal treatment following partial meniscectomy in a clinical setting and detected meniscus regeneration and improvement in knee pain (Vangsness Jr. et al 2014).…”

Novel multilayer meniscal scaffold provides biomechanical and histological results comparable to polyurethane scaffolds: An 8 week rabbit study

“…Recently; bone marrow stem cell impregnated silk fibroin scaffolds showed better feasibility in terms of structure and function in a rabbit model 22 . Koch et al also reported accelerated meniscal healing withpolyurethane scaffolds loaded with mesenchymal stromal cells 23 . Similarly platelet derived growth factor (PDGF)-coated meniscus scaffolds demonstrated increased migration of meniscal cells and consequently improved biomechanical properties 24 …”

The Importance of the Knee Joint Meniscal Fibrocartilages as Stabilizing Weight Bearing Structures Providing Global Protection to Human Knee-Joint Tissues

“…A number of animal models have been employed in these studies including goats [83], rabbits [92,93], minipigs [69,94], sheep [84,85,86,87,88,95] and rats [26,29,63,96]. MSCs have been sourced from bone marrow [95,97,98,99,100,101], adipose tissues [98,99,102,103] and synovium [62,94,98,103]. The utility of a number of bioscaffolds seeded with therapeutic cells have also been examined to promote repair of inner zone meniscal defects (reviewed in [18]).…”

“…These scaffolds include a stem cell/collagen-derived scaffold [91], polyurethane [104] and a scaffold-free tissue-engineered construct derived from allogeneic synovial MSCs [98] besides a number of conventional tissue engineering synthetic resorbale bioscaffolds [105]. Fibrin-glue has also been evaluated as a cell delivery vehicle for meniscal repair [89,97,103,106]. Examination of the cell directive properties of MSCs over meniscal cells co-cultured in scaffold free micromass pellet cultures has demonstrated a significant increase in cellular proliferation, type I and II collagen and aggrecan production [105].…”