Bioactive scaffolds based on collagen filaments with tunable physico-chemical and biological features.

Native tissues such as nerve bundles, blood vessels and tendons have extracellular matrices with a characteristic linear orientation, which cannot be fully achieved with the current technology for the development of regenerative biomaterials. In this study, bioactive and oriented collagen filaments have been fabricated using a combination of wet-spinning and carbodiimide-based crosslinking. The wet-spinning techniques, including extrusion and collection rates, and their influences on collagen filaments were studied and optimized. The diameter of the attained collagen filaments can be adjusted ranging from 30 µm to 650 µm. Further characterizations, such as circular dichroism, scanning electron microscopy, small-angle X-ray scattering and Fourier transform infrared spectra analysis, showed that the native structure of the collagen was greatly preserved after the filament preparation process. The measurements of weight swelling ratio and degradation rate indicate that the crosslinking method can efficiently regulate the physico-chemical properties of collagen filaments, including water absorption and degradation behaviors. In particular, the mechanical strength of collagen filaments can be greatly improved via crosslinking. In addition, cells can adhere and spread on collagen filaments in well-aligned patterns, showing appropriate biological features. It can be concluded that the bioactive collagen filaments with tunable properties are preferable for developing tissue engineering scaffolds with characteristic orientation features. With further study of the interactions between collagen filaments and cells, this work may shed light on the development of collagen based biomaterials that would be beneficial in the field of tissue engineering.

Canine ACL reconstruction with an injectable hydroxyapatite/collagen paste for accelerated healing of tendon-bone interface.

Healing of an anterior cruciate ligament (ACL) autologous graft in a bone tunnel occurs through the formation of fibrovascular scar tissue, which is structurally and compositionally inferior to normal fibrocartilaginous insertion and thus may increase the reconstruction failure and the rate of failure recurrence. In this study, an injectable hydroxyapatite/type I collagen (HAp/Col Ⅰ) paste was developed to construct a suitable local microenvironment to accelerate the healing of bone-tendon interface. Physicochemical characterization demonstrated that the HAp/Col Ⅰ paste was injectable, uniform and stable. The in vitro cell culture illustrated that the paste could promote MC3T3-E1 cells proliferation and osteogenic expression. The results of a canine ACL reconstruction study showed that the reconstructive ACL had similar texture and color as the native ACL. The average width of the tunnel, total bone volume, bone volume/tissue volume and trabecular number acquired from micro-CT analysis suggested that the healing of tendon-bone interface in experimental group was better than that in control group. The biomechanical test showed the maximal loads in experimental group achieved approximately half of native ACL's maximal load at 24 weeks. According to histological examination, Sharpey fibers could be observed as early as 12 weeks postoperatively while a typical four-layer transitional structure of insertion site was regenerated at 48 weeks in the experimental group. The injectable HAp/Col Ⅰ paste provided a biomimetic scaffold and microenvironment for early cell attachment and proliferation, further osteogenic expression and extracellular matrix deposition, and in vivo structural and functional regeneration of the tendon-bone interface.

In vivo Evaluation of Fibrous Collagen Dura Substitutes.

Dura substitutes are applied in duraplasty to repair lost or damaged dura. Collagen-based dura substitutes are mainstream products in both the US and Chinese markets. In this study, dura substitute devices with potential dura regeneration ability are evaluated. The dura substitutes are composed of fibrous type I collagen that were purified from bovine tendon. Physical and chemical characterization demonstrated that the tested dura substitute has desirable porous scaffolding structures and is composed of highly purified type I collagen. The collagen dura substitutes were further investigated in vivo with a rabbit model for 6 months to evaluate their safety and performance to repair and regenerate dura. No inflammation or infection was observed during the course of in vivo study. The integration of the collagen dura substitutes with surrounding tissue was normal as compared to native tissue. The macroscopic and microscopic histological assessments of the sampled animal tissue showed that the damaged dura were regenerated. The collagen dura substitutes were resorbed between 3 and 6 months along with newly regenerated dura. Both tissue adhesion and dura repair was the worst in blank control group as compared to those in the collagen dura substitutes. Taken together, regenerative collagen dura substitutes demonstrated with suitable physicochemical properties. The in vivo evaluation in a rabbit model further demonstrated the safety and performance of such substitutes for dura repair and regeneration.