Vascularization and biocompatibility of poly(ε-caprolactone) fiber mats for rotator cuff tear repair

Abstract

Rotator cuff tear is the most frequent tendon injury in the adult population. Despite current improvements in surgical techniques and the development of grafts, failure rates following tendon reconstruction remain high. New therapies, which aim to restore the topology and functionality of the interface between muscle, tendon and bone, are essentially required. One of the key factors for a successful incorporation of tissue engineered constructs is a rapid ingrowth of cells and tissues, which is dependent on a fast vascularization. The dorsal skinfold chamber model in female BALB/cJZtm mice allows the observation of microhemodynamic parameters in repeated measurements in vivo and therefore the description of the vascularization of different implant materials. In order to promote vascularization of implant material, we compared a porous polymer patch (a commercially available porous polyurethane based scaffold from Biomerix™) with electrospun polycaprolactone (PCL) fiber mats and chitosan-graft-PCL coated electrospun PCL (CS-g-PCL) fiber mats in vivo. Using intravital fluorescence microscopy microcirculatory parameters were analyzed repetitively over 14 days. Vascularization was significantly increased in CS-g-PCL fiber mats at day 14 compared to the porous polymer patch and uncoated PCL fiber mats. Furthermore CS-g-PCL fiber mats showed also a reduced activation of immune cells. Clinically, these are important findings as they indicate that the CS-g-PCL improves the formation of vascularized tissue and the ingrowth of cells into electrospun PCL scaffolds. Especially the combination of enhanced vascularization and the reduction in immune cell activation at the later time points of our study points to an improved clinical outcome after rotator cuff tear repair.

Modulating electrospun polycaprolactone scaffold morphology and composition to alter endothelial cell proliferation and angiogenic gene response

“…This method has been used in many aspects of tissue engineering to mimic the structure of the native ECM, allowing for improved environments for cell adhesion, migration and proliferation [16,17]. Polycaprolactone (PCL) is one of the most prominently used polymers for electrospinning, due to its widely studied biocompatibility and its ease of manufacturing [18][19][20]. To treat this, approaches such as bypass grafting are implemented [21].…”

Nanofiber Scaffolds by Electrospinning for Rotator Cuff Tissue Engineering

“…Another key factor for a successful incorporation of tissue- engineered constructs is a rapid ingrowth of cells and tissues to regenerate the tendon-bone-transition. 92 Ingrowth of cells and tissues strongly depend on a rapid vascularization of the implant material for transporting nutrients, growth factors, and supporting gas exchange and removal of waste materials. Electrospun nanofiber scaffolds can be potential candidates to fulfill these criteria.…”

“…Electrospun nanofiber scaffolds can be potential candidates to fulfill these criteria. Gniesmer et al 92 tested chitosan-graft-PCL coated electrospun PCL (CS-g-PCL) fiber mats in vivo . Previously, aligned chitosan-PCL nanofibers showed promising results.…”

“…Furthermore CS-g-PCL fiber mats also showed a reduced activation of immune cells. 92 CS-g-PCL being able to improve the formation of vascularized tissue and the ingrowth of cells into electrospun PCL scaffolds is clinically meaningful. The same group further investigated the usefulness of CS-g-PCL nanofiber mats in combination of transforming growth factor beta 3 (TGF–β3) for rotator cuff healing.…”

Using Tools in Mechanobiology to Repair Tendons

“…The most common sources of naturally derived ECM used for tendon-mimetic scaffolds include small intestine submucosa, amniotic membrane [96], collagen [97], gelatin (denatured collagen) [98], glycosaminoglycans [97], silk [99], hyaluronic acid, and fibrin (described in more detail in a recent review by Freedman and Mooney [100]). Additionally, synthetic ECM has also been used for developing scaffolds for tendon repair, including poly(glycolic acid) (PGA), poly(lactic acid) (PLA), poly(ethylene glycol) (PEG) [100], poly(ε-caprolactone) (PCL) [101], and combinations of these (e.g., poly(l-lactide-co-ε-caprolactone) (PLCL) [102]), as well as polyacrylamide [100]. The selection of ECM-derived and synthetic materials for use in tendon repair depends on the wide range of mechanical properties both in tension and compression of these materials.…”