Table 4.

List of construction strategies of engineering enthesis

Biomaterials	Fabrication technique	Stimulus	Design	Scaffolds used in different organs and animals	Results	Ref.
PGA-PLCL	Electrospinning	Glycolic acid	Creation of microporous structures with fiber diameters within the nanometer range	Rotator cuff; sheep	Display an enthesis similar to protogenetic insertion without surgical complications	[92]
hDCB-ECM	Decellularization	Chemokine (SDF-1)	Graded demineralization for gradient scaffold	Rotator cuff; rabbit model	Promote stromal cell recruitment, bone and fibrocartilage formation and ultimate tensile stress	[74]
PCL/HA/ZnO	Electrospinning	1% (ITS) phalloidin	Composite films with less bacterial attachment	In vitro	Promote cell compatibility ,adhesion, osteogenesis chondrogenesis and fibrocartilage formation	[87]
CGCaP/PEG/CG	Lyophilization; cross-linking	None	Continuous triphasic scaffolds containing osseous and tendinous tissue compartments	In vitro	Dissipate interfacial strain between mechanically disparate tissue compartments	[35]
PCL–PCL/TCP–PCL/TCP	3D printing	Loading	Three phases; different cells were separately encapsulated in GelMA and loaded seriatim on the relevant phases of the scaffold	Rotator cuff; mice	Promote cell seeding, chondrogenesis, and matrix deposition in varying phases	[77]
Tissue-specific ECM; AP	Electrospinning	ECM-derived components	Multiphasic scaffold; distal region of the C-ECM coated fibers additionally functionalized with an apatite layer	In vitro	Promote MSC differentiation, cartilage template development toward different tissues	[107]
ECM	Decellularization	HAp (mineral content)	Scaffolds with mineral gradients	In vitro	Cells in matrix with higher mineral content display osteogenic behavior at earlier times than those in the unmineralized substrate	[110]
Silk fiber	Electrospinning	SBF	A nanofibrous scaffold with gradient mineral coating	Anterior cruciate ligament; rats	Enhance integration in the tendon-to-bone enthesis with a higher ultimate load and more fibrocartilaginous tissue formation	[69]
ECM	Decellularization; freezing; section	SDF-1α	A scaffold with book-shaped structures with 5 pages (about 3 × 2.5 × 0.25 mm), page thickness = 50 μm)	Rotator cuff; rats	Avoid the complex process of in vitro loading cells on the scaffold and is convenient for clinical application	[111]
KGN; GelMA	Ultraviolet crosslinking; vacuum freeze-drying	Bone marrow stimulation	A KGN-loaded GelMA hydrogel scaffold	Rotator cuff; rabbits	Improve enthesis healing by promoting fibrocartilage formation and improving the mechanical properties	[45]
GelMA	3D printing	TGFβ family growth factors	A multi-phasic gelatin methacrylate hydrogel construct system for spatial presentation of proteins	In vitro	Guide heterogeneous and spatially confined changes in mesenchymal stem cell genes and protein expressions	[112]
HAp/PCL	Swelling	ASCs	A gradient scaffold patterned with an array of funnel-shaped channels	In vitro	Help form a functionally graded enthesis	[66]
PCL	Electrospinning	EM (electromagnetism)	Scaffolds contain nanofibers positioned in various direction	Rotator cuff; rats	Enhance early enthesis reconstruction	[67]
Trabecular bone	Demineralization	bfGF	A scaffold with an apatitic mineral gradient using a top-down approach	In vitro	Generate a model showing the dependence of mineral removal as function of time in the chelating solution and initial bone morphology	[75]
Melatonin; PCL	Electrospinning	TGF-b3, melatonin-PCL extracts	Melatonin-loaded aligned PCL electrospun fibrous membranes were fabricated	Rotator cuff; rats	Inhibit macrophage infiltration in the tendon-to-bone enthesis at the early healing phase, increase chondroid zone formation, promote collagen maturation, decrease fibrovascular tissue formation and improve the biomechanical strength of the regenerated enthesis	[65]
Silk fiber	[113]	None	[113]	Anterior cruciate ligament; sheep	Make ACL regeneration with a silk fiber-based scaffold with and without additional cell seeding	[84]
Titanium	3D printing	None	A lattice structure of 500 mm diamond unit cells, deep in the column and connected to the lattice on the top of the lateral surface of the ascending ramu	TMJ; patient	promote bone formation and reattach lateral pterygoid enthesis	[114]
PCL	3D printing	CTGF	Three-layered scaffolds with micro-precise spatiotemporal delivery of growth factors	Rotator cuff; rats	Show translational potential for improving outcomes after rotator cuff repair	[93]
PCL; PET	Layer-by-layer self-assembly	BMP-7 WAC	To roll up PCL nanofibrous membrane and PET mesh fabric into a ‘swiss roll’ structure	Anterior cruciate ligament; rabbits	Promote the integration of hybrid ligaments and bone tunnels	[94]