77 / 2018-07-09 03:05:26

Improved bone and cartilage regeneration in a rapid-manufactured functionally-graded osteochondral

tissue engineering scaffold,cartilage,osteochondral

全体主题 > vi. BAMOS (Biomaterials and Additive Manufacturing: Osteochondral Scaffold innovation)

Introduction
The lack of a gold standard treatment for osteochondral lesions has become a major concern in Orthopaedics as it represents a risk factor for “early onset” secondary osteoarthritis [1]. Tissue engineering approaches have shown potential in restoring joint’s function; however, in case of large defects they often result in the formation of a mechanically inferior fibrocartilage [2]. We have developed a functionally graded multi-layered scaffold to address large osteochondral defects, with focus on improving bone ingrowth and cartilage quality. This study investigated the efficacy of this scaffold in vivo following implantation in sheep knee and a clinical dog shoulder.
Materials and methods
The tri-layered scaffold was fabricated using a combination of additive manufacturing and freeze-drying techniques. Titanium lattices were fabricated using a DMLS system. The final scaffold had strut thickness of 1.5 mm, pitch size of 0.75 mm, and porosity of 72%. The middle PLA layer was manufactured using a FlashForge system. The fibers were extruded at nozzle temperature of 210°C to form a section with pore size of 0.5mm and porosity of 70% (Fig.1). A multi-layered collagen/hydroxyapatite scaffold was used as control. Ten sheep were operated on and either the scaffold or the control was implanted in the knee. The tissue was retrieved 3 months post-op. Bone ingrowth into the titanium matrix and quality of the cartilage was assessed macroscopically and histologically. The scaffold was also implanted in a clinical dog shoulder in collaboration with Prof. Fitzpatrick. Arthroscopic and histological examinations were performed 3 months and 1.5 years post-op, respectively.

Fig. 1 Representation of scaffold and individual layers
Results
In our clinical dog study, arthroscopic examinations revealed formation of a smooth cartilage and restoration of joint’s curve. In the sheep study, it was observed that gross morphological appearance of regenerated cartilage was superior in the scaffold group compared to the control group. Collagen-II and Safranin-O stainings confirmed formation of a hyaline-like cartilage in the scaffold group. Histological examinations revealed that the bone ingrowth was significantly higher (p=0.01) in the scaffold group (~40%) than that in the control group (~15%).

Fig. 2 Cartilage and bone regeneration in dog shoulder and sheep knee using scaffold.
Conclusions
We have demonstrated that using a rapid manufacturing technique, a functionally graded scaffold can be fabricated that supports bone growth and smooth/homogenous cartilage formation. The observed enhancement in regeneration of cartilage in both animal models is believed to be due to the strong support provided by the Ti matrix and new bone growth into this matrix.