Biomanufacturing organized collagen-based microfibers as a Tissue ENgineered Device (TEND) for tendon regeneration

Abstract

Approximately 800, 000 surgical repairs are performed annually in the U.S. for debilitating injuries to ligaments and tendons of the foot, ankle, knee, wrist, elbow and shoulder, presenting a significant healthcare burden. To overcome current treatment shortcomings and advance the treatment of tendon and ligament injuries, we have developed a novel electrospun Tissue ENgineered Device (TEND), comprised of type I collagen and poly(D,L-lactide) (PDLLA) solubilized in a benign solvent, dimethyl sulfoxide (DMSO). TEND fiber alignment, diameter and porosity were engineered to enhance cell infiltration leading to promote tissue integration and functional remodeling while providing biomechanical stability. TEND rapidly adsorbs blood and platelet-rich-plasma (PRP), and gradually releases growth factors over two weeks. TEND further supported cellular alignment and upregulation of tenogenic genes from clinically relevant human stem cells within three days of culture. TEND implanted in a rabbit Achilles tendon injury model showed new in situ tissue generation, maturation, and remodeling of dense, regularly oriented connective tissue in vivo. In all, TEND’s organized microfibers, biological fluid and cell compatibility, strength and biocompatiblility make significant progress towards clinically translating electrospun collagen-based medical devices for improving the clinical outcomes of tendon injuries.

Advanced Nanofiber-Based Scaffolds for Achilles Tendon Regenerative Engineering

“…The injection in the rabbit AT injury model revealed that LP-PRP and LR-PRP improved AT recovery more than LP-PRP ( Yan et al, 2017 ). Maghdouri-white et al developed a novel type of TEND consisting of PDLLA and type I collagen ( Maghdouri-White et al, 2021 ). For 2 weeks, annealed TEND rapidly adsorbs PRP and gradually releases PDGF-BB and TGF-β1.…”

The Silk, Versatile Material for Biological, Optical, and Electronic Fields: Review

“…TEND (Tissue Engineered Device), obtained by mixing type 1 collagen and PDLLA (poly DL-lactide) solubilized in DMSO (dimethyl sulfoxide), represents an effective solution. The morphological dimensioning of this structure allows improving cell adhesion, ensuring tissue integration and mechanical resistance [99].…”

Effect of Mammalian Tissue Source on the Molecular and Macroscopic Characteristics of UV-Cured Type I Collagen Hydrogel Networks

“…Molecular alignment, fibrillary organisation, and covalent crosslinking of collagen molecules are key in dictating the macroscopic properties of specific biological tissues in vivo [1] and have been widely pursued for the development of functional collagen-based biomaterials and medical devices. In light of its major role in wound healing and tissue remodelling, collagen has therefore been successfully applied in wound dressings [3,4], guided bone regeneration membranes [5], tendon repair scaffolds [6], pelvic reconstruction meshes [7,8], as well as tracheal [9,10] and corneal [11] implants. Consequently, multiple design strategies, including blending with synthetic polymers [12], fibre spinning [13], and covalent crosslinking [14], have been developed for a range of collagen raw materials generating varying preclinical success.…”