Linear Ordered Collagen Scaffolds Loaded with Collagen-Binding Basic Fibroblast Growth Factor Facilitate Recovery of Sciatic Nerve Injury in Rats

Abstract

Natural biological functional scaffolds, consisting of biological materials filled with promoting elements, provide a promising strategy for the regeneration of peripheral nerve defects. Collagen conduits have been used widely due to their excellent biological properties. Linear ordered collagen scaffold (LOCS) fibers are good lumen fillers that can guide nerve regeneration in an ordered direction. In addition, basic fibroblast growth factor (bFGF) is important in the recovery of nerve injury. However, the traditional method for delivering bFGF to the lesion site has no long-term effect because of its short half-life and rapid diffusion. Therefore, we fused a specific collagen-binding domain (CBD) peptide to the N-terminal of native basic fibroblast growth factor (NAT-bFGF) to retain bFGF on the collagen scaffolds. In this study, a natural biological functional scaffold was constructed using collagen tubes filled with collagen-binding bFGF (CBD-bFGF)-loaded LOCS to promote regeneration in a 5-mm rat sciatic nerve transection model. Functional evaluation, histological investigation, and morphometric analysis indicated that the natural biological functional scaffold retained more bFGF at the injury site, guided axon growth, and promoted nerve regeneration as well as functional restoration.

Gelatin-methacrylamide gel loaded with microspheres to deliver GDNF in bilayer collagen conduit promoting sciatic nerve growth

“…Collagen, a primary constituent of natural extracellular matrix, has been employed as material of scaffolds for tissue engineering due to many excellent properties: low antigenicity, promotion of cell attachment, and full bioabsorption. 7,8 Bio-Gide ® is a kind of bilayer collagen membrane derived from porcine dermis. 9 Moreover, it has been approved by the US Food and Drug Administration and widely used in clinics for guided tissue/bone regeneration.…”

“…[11][12][13] However, if combined with growth factors or seed cells, nerve regeneration will get better outcome. 8,14 It is an important yet-to-be-solved problem about how to combine scaffold with growth factors or seed cells to establish an optimal microenvironment efficiently and effectively.…”

Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats

“…Its ingredient, heparin, showed high affinity to a variety of GFs [27], allowing it to carry bFGF and NGF to cell-surface receptors to enhance intracellular signal transduction. Furthermore, while GFs have shown convincing efficacy when administered alone with/without biomaterials [22,23,28,29], the regeneration of injured peripheral nerves is a dynamic process that requires several GFs and cytokines to stimulate axonal outgrowth and remodeling of the intracellular cytoskeleton [30], so single GF administration are unlikely to adequately satisfy the curative demands of patients with multi-illnesses [31]. …”

Tissue engineering of the peripheral nervous system

“…These growth factors have some limitations that could be solved by the use of controlled delivery systems, where they are efficiently immobilized or cross-linked into NC and/or intraluminal fillers [139,145,147,[152][153][154][155]. These studies also demonstrate that the combined use of physical fillers and growth factors or the combination of two growth factors provide a synergetic effect to the regenerative microenvironment, promoting a comparable nerve regeneration to the use of autograft [140,141,146,148,153,158,160].…”

“…NC were also functionalized by the incorporation of growth factors and/or essential ECM and/or peptide sequences within the biomaterials. These growth factors were incorporated within the NCs wall [144][145][146][147][148], encapsulated into intraluminal biodegradable microspheres [149][150][151][152] and combined with aligned biomaterials [68,117,[153][154][155]. The incorporation of chitosan and chondroitin sulfate into the wall of the poly-DL-lactic acidbased NC showed an improvement of the nerve regeneration, but comparable results to the autograft were only obtained by the immobilization of NGF into the inner NCs wall [148].…”