Scaffold-Based Gene Therapeutics for Osteochondral Tissue Engineering

Abstract

Significant progress in osteochondral tissue engineering has been made for biomaterials designed to deliver growth factors that promote tissue regeneration. However, due to diffusion characteristics of hydrogels, the accurate delivery of signaling molecules remains a challenge. In comparison to the direct delivery of growth factors, gene therapy can overcome these challenges by allowing the simultaneous delivery of growth factors and transcription factors, thereby enhancing the multifactorial processes of tissue formation. Scaffold-based gene therapy provides a promising approach for tissue engineering through transfecting cells to enhance the sustained expression of the protein of interest or through silencing target genes associated with bone and joint disease. Reports of the efficacy of gene therapy to regenerate bone/cartilage tissue regeneration are widespread, but reviews on osteochondral tissue engineering using scaffold-based gene therapy are sparse. Herein, we review the recent advances in gene therapy with a focus on tissue engineering scaffolds for osteochondral regeneration.

Hydrogel-Based Localized Nonviral Gene Delivery in Regenerative Medicine Approaches—An Overview

“…Further, compared with recombinant growth factors that exhibit half-life in the range of minutes and a rapid inactivation in physiological conditions, gene therapy offers the possibility of directly transferring genes encoding for the therapeutic factor into the target cell population [20]. Therefore, by transfecting specific gene sequences into cells, overexpressing, or silencing the original gene, their biological functions can be regulated to achieve the desired effect [21].…”

Advances in the Application of Supramolecular Hydrogels for Stem Cell Delivery and Cartilage Tissue Engineering

“…A comprehensive review of recent advances in cartilage tissue engineering based on scaffolds combined with different genetically modified MSCs is found in our previous work (Yan et al, 2019). In this section, the focal point is the latest research progress in supramolecular hydrogels in cartilage tissue engineering applications.…”

Recent advances in polymeric biomaterials-based gene delivery for cartilage repair

“…Because nucleic acids require effective cell uptake to pass through cell membrane and cytoplasm for efficient transfection and expression, vectors are required for effectively delivering gene of interest for cartilage regeneration [ 8 ]. As a bridge of exogenous target genes enter cells to induce cartilage regeneration in situ , the vectors in delivery system directly determine the success or failure of treatment.…”

“…All these drawbacks led to the emergence of tissue engineered cartilage grafts, which have given many promising results and tremendous progress. However the generation of ideal biomimetic synthetic chondral and osteochondral replacements is still elusive, and in fact, many challenges remain [ 7 , 8 ]. For example, 1) the recombinant proteins used in tissue engineering are expensive and have a short half-life; 2) the unstable generation of chondrocyte phenotypes and the mechanical properties of engineered cartilage are hardly consistent with peripheral cartilage, which may vary greatly with age, weight, or tissue location; 3) it is difficult to achieve simultaneous differentiation into bone and cartilage, resulting in ineffective integration with surrounding normal tissue and subchondral bone.…”

“…Physiological gene therapy might overcome these barriers because it allows to continuously express therapeutic gene products, generate intricate structure of the osteochondral unit at the defect and functionally promote the formation of new cartilage [ 9 , 10 ]. However, direct injection of genes or gene complexes into the joint is limited by the fixed action sites, dilution of synovial fluid and apoptosis of transfected cells [ 8 , 11 ]. Biomaterials-guided gene delivery thus has been adapted to improve the spatiotemporal effects of gene products, as biomaterials can protect the therapeutic genes from degrading of enzymes, also allow them being delivered gradually and controllably.…”