A macro- and micro-designed chitosan-alginate scaffold with sustained growth factor release for chondrogenesis.

摘要

Cartilage regeneration is a promising field with many attempts at creating a tissue-engineered cartilage substitute. While many tissue-engineered skin and bone products exist and continue to enter the market, there remains no FDA-approved solution to regenerate the avascular, aneural cartilage tissue other than autologous chondrocyte implantation, which is both costly and requires weeks of cell culture time, not to mention healthy cartilage from which to harvest the chondrocytes. Many attempts to create biomaterial scaffolds for implantation are being made, yet these technologies often require seeded cells, and the resulting cartilage (if there is proper cartilage regeneration and not fibrocartilage production) often lacks the zonal architecture that gives native cartilage its unique structural and functional properties. Lots of recent focus has been given to growth factor delivery from within scaffolds to assist cartilage regeneration, specifically to signal ECM production by chondrocytes. However, most diffusion-based growth factory delivery systems suffer from a large burst release and do not provide a sustained release over the course of many weeks, which is required for cartilage production. Materials with growth factors chemically conjugated to their surface offer some advantage of a gradual release as the bulk material degrades and permanent presentation of the bioactive molecule, but certain growth factors require internalization for activation of their signaling cascades and conjugation chemistry to surfaces can be inefficient or render the protein biologically inactive. This project aims to develop an acellular scaffold implant with biomimetically designed micro- and macro-architecture that also delivers a chondrogenic growth factor via a sustained release mechanism to promote cartilage regeneration. This scaffold would be implanted into the joint during resurfacing and would facilitate the instant uptake of underlying bone marrow and residing mesenchymal stem cells, which would then be guided to differentiate into chondrocytes once in contact with the slowly diffusing chondrogenic growth factor. This system would address the many challenges facing cartilage tissue engineers today and has the potential to become an off-the-shelf solution for cartilage regeneration.