Muhammad Aa’zamuddin Ahmad Radzi

Tissue engineering of articular cartilage: From bench to bed-side

Degeneration or defect of articular cartilage is a major predicament and if it is left untreated, it may lead to progressive damage and disability affecting every one disregard of their age. Although nonsurgical management of articular cartilage injury has remained largely the same over many years, surgical treatment keeps on evolving. Restorative techniques, mainly the cell-based therapies and autologous or allograft transplants continue to expand, giving surgeons more options for biologic reconstruction of the articular surfaces. Hence the field of articular cartilage tissue engineering which seeks to repair, restore and improve injured or diseased articular cartilage functionality has aroused deep interest and holds great potential for improving articular cartilage therapy. However despite this great evolution, therapeutic uncertainty in the restoration of damaged cartilage using tissue engineering approaches still remains unclear for the surgeon treating patients to make evidence-based decisions. This paper will give a general idea to different level of audiences in understanding the concept of tissue engineering from bench to bed-side regarding recent developments in this exciting field.

The potential of 3-dimensional construct engineered from poly(lactic-co-glycolic acid)/fibrin hybrid scaffold seeded with bone marrow mesenchymal stem cells for in vitro cartilage tissue engineering.

Articular cartilage is well known for its simple uniqueness of avascular and aneural structure that has limited capacity to heal itself when injured. The use of three dimensional construct in tissue engineering holds great potential in regenerating cartilage defects. This study evaluated the in vitro cartilaginous tissue formation using rabbits bone marrow mesenchymal stem cells (BMSCs)-seeded onto poly(lactic-co-glycolic acid) PLGA/fibrin and PLGA scaffolds. The in vitro cartilaginous engineered constructs were evaluated by gross inspection, histology, cell proliferation, gene expression and sulphated glycosaminoglycan (sGAG) production at week 1, 2 and 3. After 3 weeks of culture, the PLGA/fibrin construct demonstrated gross features similar to the native tissue with smooth, firm and glistening appearance, superior histoarchitectural and better cartilaginous extracellular matrix compound in concert with the positive glycosaminoglycan accumulation on Alcian blue. Significantly higher cell proliferation in PLGA/fibrin construct was noted at day-7, day-14 and day-21 (p<0.05 respectively). Both constructs expressed the accumulation of collagen type II, collagen type IX, aggrecan and sox9, showed down-regulation of collagen type I as well as produced relative sGAG content with PLGA/fibrin construct exhibited better gene expression in all profiles and showed significantly higher relative sGAG content at each time point (p<0.05). This study suggested that with optimum in vitro manipulation, PLGA/fibrin when seeded with pluripotent non-committed BMSCs has the capability to differentiate into chondrogenic lineage and may serve as a prospective construct to be developed as functional tissue engineered cartilage.

Fabrication and characterization of three-dimensional poly(lactic acid-co-glycolic acid), atelocollagen, and fibrin bioscaffold composite for intervertebral disk tissue engineering application

The use of synthetically derived poly(lactic-co-glycolic acid) scaffold and naturally derived materials in regeneration of intervertebral disks has been reported in many previous studies. However, the potential effect of poly(lactic-co-glycolic acid) in combination with atelocollagen or fibrin or both atelocollagen and fibrin bioscaffold composite have not been mentioned so far. This study aims to fabricate and characterize three-dimensional poly(lactic-co-glycolic acid) scaffold incorporated with (1) atelocollagen, (2) fibrin, and (3) both atelocollagen and fibrin combination for intervertebral disk tissue engineering application. The poly(lactic-co-glycolic acid) without any natural, bioscaffold composites was used as control. The chemical conformation, morphology, cell–scaffold attachment, porosity, water uptake capacity, thermal properties, mechanical strength, and pH level were evaluated on all scaffolds using attenuated total reflectance Fourier transform infrared, scanning electron microscope, gravimetric analysis, swelling test, differential scanning calorimetry, and Instron E3000, respectively. Biocompatibility test was conducted to assess the intervertebral disk, annulus fibrosus cells viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The attenuated total reflectance Fourier transform infrared results demonstrated notable peaks of amide bond suggesting interaction of atelocollagen, fibrin, and both atelocollagen and fibrin combination into the poly(lactic-co-glycolic acid) scaffold. Based on the scanning electron microscope observation, the pore size of the poly(lactic-co-glycolic acid) structure significantly reduced when it was incorporated with atelocollagen and fibrin. The poly(lactic-co-glycolic acid)–atelocollagen scaffolds demonstrated higher significant swelling ratios, mechanical strength, and thermal stability than the poly(lactic-co-glycolic acid) scaffold alone. All the three bioscaffold composite groups exhibited the ability to reduce the acidic poly(lactic-co-glycolic acid) by-product. In this study, the biocompatibility assessment using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cells proliferation assay demonstrated a significantly higher annulus fibrosus cells viability in poly(lactic-co-glycolic acid)–atelocollagen–fibrin compared to poly(lactic-co-glycolic acid) alone. The cellular attachment is comparable in poly(lactic-co-glycolic acid)–atelocollagen–fibrin and poly(lactic-co-glycolic acid)–fibrin scaffolds. Overall, these results may suggest potential use of poly(lactic-co-glycolic acid) combined with atelocollagen and fibrin bioscaffold composite for intervertebral disk regeneration.