Table 2.

Summary of the application of different carrier materials in BTE.

Materials	Advantages	Disadvantages	Common Types	Application	References
Hydrogels	Similar to the 3D environment in vivo Effectively encapsulate EVs to maintain local concentrations and enhance EVs performance Effectively fill irregular defect environment Release EVs slowly and sustainably Targeted transport, reducing loss and ectopic effect Good biocompatibility and chemical activity	Poor mechanical properties Poor stability Inadequate adhesion of cell Failure of long-term retained of EVs	Natural materials, (Gelatin; HA-Gel; chitosan) Synthetic polymers, (PEG)High-performance composite hydrogels, (modified injectable thermosensitive hydrogels; composite hydrogels with enhanced mechanical properties)	Enhancing the performance of hydrogels(modifying hydrogels; combination application of different hydrogels) Improving the transport efficiency of EVs (adding fixed peptides; construction of fusion polypeptides)	[29,57,58,59,60,61,62,63,64,65,66,67,72]
Scaffolds	The 3D pore structure is similar to natural bone and provides space for the growth and vascularization of new tissue Good mechanical properties Absorbable and biodegradable Specific inducible surface stimuli enhance the activity of EVs	Failure of EVs Slow releasing Risk of missing the target Unable to provide similar living environments in vivo Poor effect of filling irregular voids	Classical scaffold materials (collagen sponge, bone cement scaffold, BG; β-TCP, HA scaffolds; polymer scaffolds) Innovative synthetic scaffolds	Enhancing the activity of EVs (preconditioning MSCs;inducing the expression of osteogenic related genes or proteins; combined with small molecule drugs and inducible factors such as siRNAs (externally and externally loaded)) Realizing the slow and sustained release of EVs(innovative synthetic scaffolds; scaffold materials combined with other materials;scaffold materials that provides EVs lyophilization protection)	[19,22,77,78,88,89,90,92,98,102,103,104,105,106,111,113]
Hydrogels + Scaffolds	Effectively encapsulate EVs and enhance EVs activity Sustain and slow release of EVs Effective and efficient delivery of EVs Good effect of filling bone defects Stable mechanical properties Good biocompatibility Long-term retained of EVs	The synthesis of composite materials is complicated The quality of application varies	Hydrogels filling into scaffold materials (HA-Gel hydrogels combined with nHP scaffolds; PLGA-PEG-PLGA gel microspheres combined with PLLA scaffolds) Forming new composite materials (omposite material PG/TCP; Self-healing composites)	Various new composite materials with good mechanical properties, such as self-healing, stability, adhesion and antibacterial abilities, were obtained	[47,56,77,78,115,117,118,119]