Functional Multichannel Poly(Propylene Fumarate)‐Collagen Scaffold with Collagen‐Binding Neurotrophic Factor 3 Promotes Neural Regeneration After Transected Spinal Cord Injury

Abstract

Many factors contribute to the poor axonal regrowth and ineffective functional recovery after spinal cord injury (SCI). Biomaterials have been used for SCI repair by promoting bridge formation and reconnecting the neural tissue at the lesion site. The mechanical properties of biomaterials are critical for successful design to ensure the stable support as soon as possible when compressed by the surrounding spine and musculature. Poly(propylene fumarate) (PPF) scaffolds with high mechanical strength have been shown to provide firm spatial maintenance and to promote repair of tissue defects. A multichannel PPF scaffold is combined with collagen biomaterial to build a novel biocompatible delivery system coated with neurotrophin-3 containing an engineered collagen-binding domain (CBD-NT3). The parallel-aligned multichannel structure of PPF scaffolds guide the direction of neural tissue regeneration across the lesion site and promote reestablishment of bridge connectivity. The combinatorial treatment consisting of PPF and collagen loaded with CBD-NT3 improves the inhibitory microenvironment, facilitates axonal and neuronal regeneration, survival of various types of functional neurons and remyelination and synapse formation of regenerated axons following SCI. This novel treatment strategy for SCI repair effectively promotes neural tissue regeneration after transected spinal injury by providing a regrowth-supportive microenvironment and eventually induces functional improvement.

Tailoring synthetic polymeric biomaterials towards nerve tissue engineering: a review

“…The major limitation of PPF is its viscous liquid at room temperature that, in turn, is resulted in cumbersome handling of this polymer. The unique properties of PPF-based Polymers such as biocompatibility, absorbability, injectability, and biodegradability provide the possibility for their extensive usages in biomedicine fields such as scaffolds for tissue regeneration and controlled nanodrug delivery system, preparation of orthopaedic implants and nano-vehicles for cell transplantation [80].…”

“…To illustrate this concept, Chen et al combined PPF with collagen biomaterial to provide biocompatible scaffold with high mechanical strength and minimum deformation in a short period compared to collagen alone. They observed that multichannel PPF-Collagen scaffold with collagen-binding neurotrophic factor 3 provides more efficient regrowth-supportive microenvironment for guiding neural tissue regeneration and inhibition of fibrotic scar formation following SCI compared to control, PPF and PPF-Collagen groups (Figure 8) [80].…”

Engineered 3D Polymer and Hydrogel Microenvironments for Cell Culture Applications

“…Copolymerization with PEG has been one popular approach [134], while surface functionalization with peptides also improves cell attachment, allowing applications in drug delivery and cell culturing [120]. Other functional coatings include arginine-glycine-aspartate peptides to support proliferation of human chondrocytes for cartilage tissue engineering [124,135], as well as PPF scaffolds loaded with collagen and coated with neurotrophin-3 to promote bioactivity and specifically the growth and proliferation of neurons and axons [136]. Apart from offering structural support and pores for neuronal regrowth, the stiff PPF scaffold also provided mechanical cues guiding cells to grow in specific directions [136].…”

“…PCL (4. Human chondrocytes for cartilage tissue engineering [124,135]; Neurotrophin-3 for neurons and axons [136]; Adipose stem cell adhesion for tissue regeneration [137];…”

Application of stem cells and chitosan in the repair of spinal cord injury

“…Diverse neurotrophic factors have contributed to the poor axonal regrowth and ineffective functional recovery in the SCI repair process (Chen et al, 2018a,2018b; Mesentier‐Louro et al, 2019). It has been reported that glial cell line‐derived neurotrophic factor (GDNF) has protective potential in neurodegeneration disease(Mukhamedshina et al, 2016).…”