Table 4.

Mechanisms impeding lateral integration in cartilage repair.

Mechanism	Contributing Parameters/Attributes	Examples/Previous Evidence
Cellular factors	Chondrocyte viability: Cell death hinders integration between neo-cartilage and existing tissue.	- Significant cell death reported at the interface between host and repaired tissue in partial-thickness chondral defects. - In vitro wounding induces a zone of cell death characterized by necrosis and apoptosis.
	Chondrocyte phenotype: Dedifferentiation during expansion compromises chondrocyte function.	- Dedifferentiated chondrocytes show limited redifferentiation capacity, affecting integration. - Incomplete redifferentiation can compromise normal chondrocyte function.
Donor-related factors	Donor age: Age-related decline in chondrocyte function impedes integration.	- Age-related reductions in chondrocyte function affect repair outcomes. - Young tissue exhibits better repair and integration outcomes compared to aged tissue.
	Developmental origins: Differences in tissue origin affect biosynthetic capacities and matrix production.	- Tissues from different developmental origins may have varied integration capacities. - Mixing tissues from different origins may or may not result in segregation.
Extracellular matrix factors	Collagen network: Collagen deposition and crosslinking influence integration.	- Collagenase treatment enhances integration by promoting collagen deposition and chondrocyte migration. - Lysyl-oxidase-mediated crosslinking affects fusion between cartilages.
	Proteoglycans: The presence of proteoglycans inhibits chondrocyte migration and integration.	- Enzymatic removal of proteoglycans increases chondrocyte mobility and enhances integration. - Loss of proteoglycans using chemical crosslinkers enhances adhesion of cartilage surfaces.
Biomaterials and scaffold integration	Low adhesion performance: Inadequate scaffold adhesion affects tissue integration.	- Scaffolds with poor adhesion may fail to properly integrate with surrounding cartilage. - Low adhesion can result in delamination of the repaired tissue from the host cartilage.
	Inappropriate mechanical properties: Scaffold properties may not match physiological requirements, impacting integration.	- Scaffolds with mismatched mechanical properties may lead to mechanical failure and hinder integration. - Biomechanically weak scaffolds may collapse under load, preventing integration.
	Inadequate biocompatibility: Scaffold materials may elicit immune responses or cytotoxic effects, impeding integration.	- Biocompatibility issues with scaffold materials can lead to inflammation and hinder tissue integration. - Cytotoxicity of scaffold components may impair chondrocyte function and integration.
	Insufficient porosity: Low porosity limits cell infiltration and nutrient exchange, affecting integration.	- Scaffolds with inadequate porosity may restrict cell migration and proliferation, hindering tissue integration. - Poor nutrient exchange due to low porosity can impair cell viability and integration.