Facilitated Endogenous Repair: Making Tissue Engineering Simple, Practical, and Economical

Abstract

Facilitated endogenous repair is a novel approach to tissue engineering that avoids the ex vivo culture of autologous cells and the need for manufactured scaffolds, while minimizing the number and invasiveness of associated clinical procedures. The strategy relies on harnessing the intrinsic regenerative potential of endogenous tissues using molecular stimuli, such as gene transfer, to initiate reparative processes in situ. In the simplest example, direct percutaneous injection of an osteogenic vector is used to stimulate bone healing. If necessary, additional progenitor cells and space-filling scaffolds can be provided by autologous bone marrow, muscle, fat, and perhaps other tissues. These can be harvested, processed, and reimplanted by simple, expedited, intraoperative procedures. Examples of repair of experimental osseous and osteochondral lesions in laboratory animals are described. If successful, these strategies will provide methods for tissue regeneration that are not only effective but also inexpensive, safe, and clinically expeditious. Although orthopaedic examples are given here, the technology should be more generally applicable.

Endochondral Ossification for Enhancing Bone Regeneration: Converging Native Extracellular Matrix Biomaterials and Developmental Engineering In Vivo

“…25,46,47,116 Some strategies for stimulating isolated stem cells include the use of inductive and conductive signaling molecules, either in purified form (e.g., BMP-2) 114,115 or from extracted endogenous tissue and fluids (e.g., PRP). 117 Kitamura et al 117 showed histological and mechanical evidence that BMSCs loaded with PRP regenerated bone in a dog mandible defect model comparable to autologous bone controls.…”

RECENT RESEARCH ON THE GROWTH PLATE: Mechanisms for growth plate injury repair and potential cell-based therapies for regeneration

“…Since bone formation and bony repair occur rapidly within the growth plate injury site (starting after 1 week following the injury), there is the possibility that the long length of time it takes for MSC harvest, in vitro expansion and implantation could limit the usefulness of this in vitro MSC expansion/transplantation cell-based therapy for growth plate regeneration initially after growth plate injuries. Ultimately, potential mobilisation and use of a patient's own endogenous MSCs to regenerate the growth plate injury site immediately following injury would be ideal with the development of an in situ endogenous progenitor cell therapy, which can potentially circumvent all these limitations of the in vitro MSC approach (De Bari et al 2003, Evans et al 2007) as well as the need for the surgical removal of the formed bony repair tissue later on. However, more work in future on this area is needed to identify the most optimal signals and support to mobilise sufficient amounts of endogenous MSCs into the growth plate injury site and promote their expansion and cartilage regeneration at the growth plate injury site.…”

Articular cartilage repair by genetically modified bone marrow aspirate in sheep

“…In contrast to more complex approaches in tissue engineering, we advocate the use of simpler methods that harness the intrinsic regenerative potential of endogenous tissues, using biological stimuli to initiate and promote natural healing in situ. This concept has been termed facilitated endogenous repair by Evans et al 46 and the ultimate goal is to enable clinicians to use tissue engineering that is not only successful but also cheap, safe and clinically expeditious. The proposed method is a single-step procedure that can be easily implemented in standard clinical settings, avoids the usual drawbacks associated with gene therapy because it is administered locally, and excludes the expensive in vitro production of autologous and engineered tissues.…”