Optimizing mesenchymal stem cell therapy for tendon-bone healing: Multifaceted approaches and future directions

Table 2 Summary of biomaterial-enhanced stem cell therapy for tendon-bone healing

Ref.	Biomaterial	Material type	Cell type	Functions	Model
Chen et al[47], 2020	3D-printed PLGA scaffolds	Conventional biological scaffolds	Rabbit BMSCs	Support cell growth and differentiation	Rabbit RCT model
Yea et al[48], 2020	Hydroxyapatite-gradient scaffold	Conventional biological scaffolds	hUC-MSCs	Support cell adhesion, migration, and proliferation, promoting osteogenic and chondrogenic differentiation	Rat RCT model
Han et al[49], 2023	CS-FS	Conventional biological scaffolds	Rabbit BMSCs and TSPCs	Enhance cell differentiation and activity, maintaining the phenotype	Rat and rabbit RCT models
Zhang et al[50], 2024	Magnetically seeded biphasic scaffold	Conventional biological scaffolds	SPIO-BMSCs	Increase cell seeding efficiency, promote cell distribution and concentration, and enhance chondrogenic differentiation	Rat RCT model
Ji et al[53], 2023	Cocktail-like gradient gelatin/hyaluronic acid	Hydrogel-based materials	Rat BMSCs	Simulate natural gradient structure, support long-term cell culture and embedding, promote cell growth and differentiation	Rat RCT model
Rothrauff et al[54], 2019	Fibrin or GelMA	Hydrogel-based materials	Rat ADSC	Promote chondrogenic differentiation	Rat RCT model
McGoldrick et al[55], 2017	ECM hydrogel	Hydrogel-based materials	Rat ADSC	Better biocompatibility, enhance repair efficacy	Rat calcaneus-Achilles tendon injury model
Shekaran et al[58], 2016	ECM	Natural biomaterials	Human BMSCs	Promote cell proliferation and osteogenic differentiation	Mouse ectopic mineralization model
Deng et al[59], 2021	ECM	Natural biomaterials	Human BMSCs	Promote macrophage secretion of osteoinductive factors, enhance osteogenic differentiation	Mouse femoral defect model
Mifune et al[61], 2013	Cell sheets	Natural biomaterials	Human ACL-derived CD34+ cell	Increase proprioceptive recovery, graft maturation, and biomechanical strength	Rat ACLR model
Chang et al[62], 2012	Cell sheets	Natural biomaterials	Rabbit PPCs	Maintain cell differentiation capacity, promote fibrocartilage formation	Rabbit ACLR model
Tang et al[63], 2020	Cell sheets combined with acellular scaffolds	Natural biomaterials	Rabbit BMSCs	Promote cell differentiation, enhance new bone and fibrocartilage formation	Rabbit patella-patellar tendon injury model
Chen et al[64], 2020	Cell sheets	Natural biomaterials	Canine USCs	Promote fibrocartilage formation, increase trabecular thickness and biomechanical strength	Canine RCT model
Matsumoto et al[65], 2021	Cell sheets	Natural biomaterials	Human ADSCs	Bone tunnel narrowing, increased biomechanical strength	Rabbit ACLR model
Yao et al[66], 2023	Cell sheets	Natural biomaterials	Rat TDSCs	Enhance bone formation and angiogenesis, regulate macrophage polarization and MMP/TIMP expression	Rat ACLR model
Wei et al[67], 2023	Cell sheets	Natural biomaterials	LDSCs with BMP-2/TGF-β1 gene insertion	Promote osteogenic and tenogenic differentiation, improve biomechanical strength, enhance tissue maturation, inhibit bone tunnel widening	Mouse ACLR model

PLGA: Poly lactic-co-glycolic acid; BMSC: Bone marrow-derived stem cell; RCT: Rotator cuff tear; hUC-MSC: Human umbilical cord-derived mesenchymal stem cell; CS-FS: Chitosan-silk fibroin scaffold; TSPC: Tendon stem progenitor cell; SPIO: Superparamagnetic iron oxide; GelMA: Methacrylated gelatin; ADSC: Adipose-derived stem cell; ECM: Extracellular matrix; ACL: Anterior cruciate ligament; ACLR: Anterior cruciate ligament reconstruction; PPC: Periosteal progenitor cell; USC: Urine-derived stem cell; TDSC: Tendon-derived stem cell; MMP: Matrix metalloproteinase; TIMP: Tissue inhibitors of metalloproteinase; LDSC: Ligament-derived stem cell; BMP-2: Bone morphogenetic protein 2; TGF: Transforming growth factor.