A major goal of tissue repair and regeneration is to develop a biological alternative in vitro for producing an implantable structure that serves as a support and speeds regenerative growth in vivo within a defect area.
In recent years biodegradable polymers such as poly (glycolic acid), poly (L-lactic acid) (PLLA) and their copolymers poly(L-lactic-co-glycolic acid) (PLGA) have been used as scaffold materials in studies of tissue formation. (Sofia et al. Journal of Biomedical Materials research 2001, 54, 139-148). Advantages of these polymers include their biocompatibility and degradability. However, PLGA can induce inflammation due to the acid degradation products that result during hydrolysis (Sofia et al. Journal of Biomedical Materials Research 2001, 54, 139-148). There are also processing difficulties with polyesters that can lead to inconsistent hydrolysis rates and tissue response profiles. Thus, there is a need for polymeric materials that have more controllable features such as hydrolysis rates, structure, and mechanical strength, while also being bioresorbable and biocompatible. Biological polymeric materials often demonstrate combinations of properties which are unable to be reproduced by synthetic polymeric materials. (Perez-Rigueiro et al. Science, 1998; 70: 2439-2447; Hutmacher D. Biomaterials 2000. 21, 2529-2543). Bone tissue is one example; scaffolds for bone tissue regeneration require high mechanical strength and porosity along with biodegradability and biocompatibility.
Several studies have shown that bone marrow stem cells (BMSCs) can differentiate along an osteogenic lineage and form three-dimensional bone-like tissue (Holy et al. J. Biomed. Mater. Res. (2003) 65A:447-453; Karp et al., J. Craniofacial Surgery 14(3): 317-323). However, there are important limitations. Some calcium phosphate scaffolds show limited ability to degrade (Ohgushi et al. 1992. In CRC Handbook of Bioactive Ceramics. T. Yamamuro, L. L. Hench, and J. Wilson, editors. Boca Raton, Fla.: CRC Press. 235-238), or degradation is too rapid (Petite et al. 2000. Nat. Biotechnol. 18:959-963.) Difficulties in matching mechanical properties to support desired function also remain an issue (Harris et al. J. Biomed. Mater. Res. 42:396-402).
Studies have also shown that BMSCs can differentiate along chondrogenic lineage and form three-dimensional cartilage-like tissue on biomaterial substrates, such as poly(lactic-co-glycolic acid) or poly-L-lactic acid (Caterson et al. 2001. J. Biomed. Mater. Res. 57:394-403; Martin et al. 2001. J. Biomed. Mater. Res. 55:229-235). However, the use of these scaffolds for cartilage formation manifests with the same limitations as observed with their use in bone engineering.
There exists a need for new biocompatible polymers, particularly polymers suitable for formation of scaffolds for mechanically robust applications such as bone or cartilage.