Leveraging “Raw Materials” as Building Blocks and Bioactive Signals in Regenerative Medicine

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

“…While it remains debatable whether native ECM represents nature's ideal biological scaffold, particularly because resident cells exhibit physiologically relevant synthesis and maintenance within it, these materials have received significant attention for their potential efficacy in the regenerative tissue market. 17,18,20,21 Traditional bone ECM strategies: ABG intrinsically involves the grafting of native bone ECM tissue with associated autologous cells into bone defects, and it remains the gold standard of treatment in bone regeneration due to its inherent osteoconductivity, osteoinductivity, and osteogenic capacity.…”

“…Native ECM biomaterials possess both conductive and inductive potential that are difficult to match with synthetic designs (e.g., non-native polymers). [17][18][19][20] In addition, it is increasingly evident that the structural components of native ECM also provide a regulatory role for key processes in cellular development and tissue regeneration. 21,45 These processes include cell adhesion, proliferation, differentiation, migration, and survival along with modulating signaling activity of soluble bioactive molecules.…”

“…These materials possess both conductive scaffold moieties and inductive signaling molecules that have been difficult to match with synthetic designs. [17][18][19][20][21] Within the realm of bone biomimetics, native ECM-based biomaterials (e.g., DBM) have been a key protagonist. 15 However, there may be underexplored potential to enhance the bone regenerative response with native ECM biomaterials that instead mimic the initial inflammatory or fibrocartilaginous ECM (i.e., ''pro-'' or ''soft'' callus) observed in the early reparative stage of the native bone fracture healing process.…”

“…Traditional strategies have approached tissue-engineered construction through a combination of factors described in the tissue engineering triad: cells, signals, and scaffolds. However, the use of ''raw'' ECM biomaterials may serve to bridge the gap between the latter two components of this triad by recognizing their integrated contribution to the local ECM, 20 potentially obviating the need for additional incorporation of cells and signaling molecules. Crucial to developmentally engineering the process of EC ossification inside an implant will not only be the selection of native biomaterials that mimic the relevant tissue's ECM composition but also materials which serve to modulate the developmental process.…”

Microsphere-Based Gradient Implants for Osteochondral Regeneration: a Long-Term Study in Sheep

“…As a translational study, growth factors were intentionally not encapsulated within the microspheres in the current study, as to avoid US FDA designation as a combination drug product, although this upgrade can be made in the future to create further product separation in a competitive market. Instead, a 'raw materials' approach was taken whereby natural materials are leveraged both as building blocks to be incorporated into regenerating tissue and as signaling molecules to elicit desirable responses from infiltrating cells [40]. Our previous studies have demonstrated favorable cell responses to chondroitin sulfate [20,[41][42], and β-TCP is a well-known building block for bone regeneration, which is more easily integrated into regenerating bone than the hydroxyapatite we have used in our previous microsphere-based scaffold studies [10,35,43].…”