Surface Modification Of PLGA/β-TCP Scaffolds For Bone Tissue Engineering

Therapies for bone defects include autografts, allografts, xenografts, and artificial substitutes such as synthetic cement, metals, and ceramics. However, all of these methods have specific problems and limitations. Autografts are limited by a lack of an adequate supply of donors and by donor site morbidity. Allografts and xenografts include problems with the potential transfer of pathogens and immune rejection. Artificial substitutes may result in stress shielding to the surrounding bone or fatigue failure of the substitutes.Limitations of current orthopedic techniques have prompted researchers to investigate alternative strategies for treatment of musculoskeletal impairments.The development of treatments for musculoskeletal injuries due to trauma or disease has been outlined as one of the primary research thrusts. With this in mind, tissue engineering is one area that could have a significant impact on future treatment of these musculoskeletal impairments.In the previous study, we have fabricated poly (lactic-co-glycolic acid) (PLGA)/β-tricalciumphosphate (β-TCP) scaffold via low-temperature deposition manufacturing (LDM). In vitro and in vivo experiments had proved that the scaffold was biodegradable, highly porous with a large surface-to-volume ratio, mechanically strong, and could be easily forged into desired shapes. However, the hydrophobic surface of PLGA was not adequate for cell attachment and growth; we had to take a complicated prewetting process for cell seeding. Therefore, it is important to modify the scaffold surface for acquiring good surface characteristics for cell attachment and proliferation.Since the scaffold surface properties play an important role in determining how cells respond to the biomaterials, the development of tissue engineering has recently focused on the surface design of biodegradable scaffolds. Several approaches, such as alkali hydrolysis treatment, plasma treatment, ion irradiation and surface coating have been developed to improve the bioactivity of the surface. As the two primary components of extracellular bone matrix, apatite and collagen have been coated on various biomaterials to promote cell behavior on the scaffold.In the present study, we designed a novel kind of three-dimensional porous hybrid biomaterial consisting of PLGA,β-TCP, collagen, and apatite. The collagen microsponges were formed in the pores of PLGA/β-TCP skeleton, and apatite particulates were deposited on the surfaces of the collagen microsponges. The PLGA/β-TCP scaffold would serve as a skeleton to facilitate the formation of the collagen sponge, while the collagen and apatite would provide the hybrid scaffold with good cell interaction and osteoconductivity.This study can be subdivided into the following parts:1. Preparation of the two variants of the PLGA/β-TCP (7:3, 6:4) scaffold by using LDM system.2. Fabricating a novel hybrid scaffold of PLGA/β-TCP skeleton, collagen, and hydroxyapatite by depositing hydroxyapatite particulates on the collagen microsponge surface.3. Examining water absorption capability of the hybrid scaffold, BMSCs proliferation and differentiation on the hybrid scaffold. The results showed that hybridization of the PLGA/β-TCP skeleton with collagen/apatite sponge increased hydrophilicity and facilitated cell seeding compared to pure PLGA/β-TCP scaffolds.4. BMSCs were seeded into the hybridized and original RP scaffold in order to repair 15 mm segmental defect in the radius of rabbits. Radiograph, Micro CT and histology were used to evaluate the scaffold degradation rate and new bone formation. The results suggested that the apatite/collagen sponge composite coating could improve the RP scaffold degradation rate and new bone formation in vivo. Bony union was observed in experimental group after 1 year postoperaion.Our research has demonstrated that cell attachment, proliferation, differentiation on PLGA/β-TCP scaffold and segmental bony defect reconstruction were greatly enhanced with apatite/collagen coating. The PLGA/β-TCP scaffold modified by apatite/ collagen sponge is expected to be of useful value in bone tissue engineering.