Injection molding of chondrocyte/alginate constructs in the shape of facial implants

Abstract

Over one million patients per year undergo some type of procedure involving cartilage reconstruction. Polymer hydrogels, such as alginate, have been shown to be effective carriers for chondrocytes in subcutaneous cartilage formation. The goal of our current study was to develop a method to create complex structures (nose bridge, chin, etc.) with good dimensional tolerance to form cartilage in specific shapes. Molds of facial implants were prepared using Silastic ERTV. Suspensions of chondrocytes in 2% alginate were gelled by mixing with CaSO(4) (0.2 g/mL) and injected into the molds. Constructs of various cell concentrations (10, 25, and 50 million/mL) were implanted in the dorsal aspect of nude mice and harvested at times up to 30 weeks. Analysis of implanted constructs indicated progressive cartilage formation with time. Proteoglycan and collagen constructs increased with time to approximately 60% that of native tissue. Equilibrium modulus likewise increased with time to 15% that of normal tissue, whereas hydraulic permeability decreased to 20 times that of native tissue. Implants seeded with greater concentrations of cells increased proteoglycan content and collagen content and equilibrium and decreased permeability. Production of shaped cartilage implants by this technique presents several advantages, including good dimensional tolerance, high sample-to-sample reproducibility, and high cell viability. This system may be useful in the large-scale production of precisely shaped cartilage implants.

The Local Matrix Distribution and the Functional Development of Tissue Engineered Cartilage, a Finite Element Study

“…Alternatively, for the same ECM content compression may also passively increase tissue properties by altering the functional organization and entanglement of the ECM network. A continuous increase in stiffness with time has been observed in several studies, 5,11,36 while others have found an initial increase followed by a plateau. 37,38,40,48 As shown in Fig.…”

“…2(b) for the model at 56 days. 11 At 12 weeks homogeneous GAG staining was observed which was attributed to alginate degradation. Related to this, the importance of matrix diffusivity has been demonstrated by modulating the degradation behavior of PEG hydrogels.…”

Long-Term Morphological and Microarchitectural Stability of Tissue-Engineered, Patient-Specific AuriclesIn Vivo

“…However, the degradation of these polymers has been reported to cause inflammatory reactions. 3,4 Natural polymer scaffolds and hydrogels, such as alginate 13 and fibrin, 14 are easily molded and have high biocompatibility, 4 but are limited by low stiffness, making them difficult to handle. 15 Chondrocytes encapsulated in alginate and then implanted also become fibrochondrogenic.…”

Shaped, Stratified, Scaffold-free Grafts for Articular Cartilage Defects

“…These methods have been used for engineering of elastic and nonarticular cartilage such as auricle [7,21,41], nose [8,21], and tympanic membrane [17]. Several shaped osteochondral constructs containing articular cartilaginous sections, for phalanx [20,35] and mandibular condyle [1], for example, have been fabricated.…”

“…In the molding approach, a mixture of cell and scaffold is placed together into a mold where the scaffold is polymerized, and the shaped construct is cultured. Scaffolds for the molding method are commonly hydrogels, including agarose [19], alginate [8], and photopolymerizable polyethylene glycol derivative [1]. While the results of these studies are promising, the resultant constructs may change from the desired shape due to growth and remodeling, and the surface contours of these constructs have not been analyzed.…”