Hybrid Biomaterials for Tissue Engineering: A Preparative Method for PLA or PLGA–Collagen Hybrid Sponges

Tissue engineering has emerged as a promising alternative approach in the treatment of malfunctioning or lost organs. In this approach, a temporary scaffold is needed to serve as an adhesive substrate for the implanted cells and a physical support to guide the formation of the new organs. Transplanted cells adhere to the scaffold, proliferate, secrete their own extracellular matrices (ECM), and stimulate new tissue formation. During this process, the scaffold gradually degrades and is eventually eliminated. Therefore, in addition to facilitating cell adhesion, promoting cell growth, and allowing the retention of differentiated cell functions, the scaffold should be biocompatible, biodegradable, highly porous with a large surface/volume ratio, mechanically strong, and malleable into desired shapes. The most commonly used three-dimensional porous scaffolds are constructed from two classes of biomaterials. One class consists of synthetic biodegradable polymers such as aliphatic polyesters, poly(glycolic acid) (PGA), poly(lactic acid) (PLA), and their copolymer of poly-(DL-lactic-co-glycolic acid) (PLGA). The other class consists of naturally derived polymers such as collagen. PLA, PGA, and PLGA are biocompatible and among the few synthetic polymers approved by the Food and Drug Administration for specific human clinical applications, such as surgical sutures and some implantable devices. They have the potential advantages of being easily formed into scaffolds having the same shape as the tissue to be replaced and, if designed with sufficient mechanical strength, can retain this structure until the new tissue forms. Their rate of biodegradation can also be tailored to match the rate of regeneration of the new tissue. The disadvantages of these synthetic polymers are the lack of cell-recognition signals, which results in insufficient cell adhesion, and hydrophobicity, which hinders even seeding of sufficient cell mass in three dimensions. In contrast, naturally derived polymers have the potential advantages of specific cell interactions and easy seeding of cells because of their hydrophilicity. However, scaffolds constructed from naturally derived polymers are mechanically unstable, and do not easily contribute to the creation of tissue structures with a specific predefined shape for transplantation. As a result, hybrid three-dimensional porous scaffolds of synthetic and naturally derived biodegradable polymers have been developed for tissue engineering. A hybrid biomaterial of collagen fibers embedded within a PLA matrix has been reported to strengthen collagen fibers for application to tendon or ligament reconstruction. A method of coating PLLA sponge (PLLA = poly-(L-lactic acid)) with collagen or embedding collagen gel within PLLA sponge has been used to improve the interaction between PLLA sponge and hepatocytes. However, the surface area/volume ratios of these hybrid biomaterials remained unchanged. A novel kind of hybrid biodegradable porous scaffold has been developed by our group by nesting collagen microsponge in the pores of poly(alpha ester) sponge. This kind of hybrid biomaterial not only retains the advantages of both biodegradable synthetic poly(alpha ester)s and naturally derived collagen, also increased the surface area/volume ratio for transplanted cells. At first, PLA or PLGA sponges were prepared by a particulate-leaching technique using sieved sodium chloride particulates or pre-prepared ice particulates as a porogen. After sodium chloride or pre-prepared ice particulates were removed by washing with water or freeze-drying, porous structures were formed. The PLA or PLGA sponge showed the same pore size and morphology as the NaCl or ice particulates that were used. Their pore structure can be controlled by adjusting the particulate size or weight ratio of NaCl or ice to the polymer. Subsequently, the PLA or PLGA sponges were immersed in type I or type II acidic collagen solutions (pH 3.2) under a vacuum so that the sponge pores filled with the collagen solution. The collagen solution-containing PLA or PLGA sponges were then frozen at ±80 C and freeze-dried to allow the formation of