Biomaterials Translational ›› 2023, Vol. 4 ›› Issue (2): 85-103.doi: 10.12336/biomatertransl.2023.02.004
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Ahlam A. Abdalla), Catherine J. Pendegrass
)
Received:
2023-02-04
Revised:
2023-03-15
Accepted:
2023-05-05
Online:
2023-06-28
Published:
2023-06-28
Contact:
Ahlam A. Abdalla,Catherine J. Pendegrass
E-mail:ahlam.abdalla.21@ucl.ac.uk;c.pendegrass@ucl.ac.uk
About author:
Catherine J. Pendegrass, c.pendegrass@ucl.ac.uk.†Present Addresses: Department of Orthopaedics & Musculoskeletal Science, Division of Surgery & Interventional Sciences, University College London, Brockley Hill, Stanmore, UK
Author | Study | Model | Tear | Intervention | Outcome measure | Results |
---|---|---|---|---|---|---|
Honda et al. | In-vivo | Rabbit | Chronic full | MSC + HA | Biomechanical, histological, and immunohistochemical analyses | Positive: Improved ultimate load and faster healing |
Jo et al. | Clinical | Human | Chronic full | BMSC + arthroscopic repeated channeling | Pain scale, ROM, muscle strength, patient satisfaction questionnaire, and functional scores. Structural integrity by MRI and CT | Positive: Enhanced structural integrity of the repair and decreased retears |
Hernigou et al. | Clinical | Human | Chronic partial | BMSC + arthroscopy | MRI | Positive: Faster complete healing/retear prevention |
Taniguchi et al. | Clinical | Human | Chronic partial | ASH + BMSC | MRI | Positive: Reduced retear rates/better integrity |
Han et al. | In-vitro, in-vivo | Rat | Acute full | PRP-infused BMSC | Expression of genes that related to tissue repair, bone formation, and tendon regeneration; | Positive: Stronger signals to angiogenesis, bone formation, and tendon generation in-situ |
Biomechanical assessment | Promoted healing in-vivo | |||||
Gulotta et al. | In-vivo | Rat | Acute full | BMSC | Biomechanical & histological analyses | Negative: No change in structure, composition, or strength |
Gulotta et al. | In-vivo | Rat | Acute full | MT1-MMP-transduced MSCs | Biomechanical & histological analyses | Positive: Better fibrocartilage formation, higher ultimate load and stress to failure, and higher stiffness |
Oh et al. | In-vivo | Rabbit | Chronic full | ADSC + suture | Electromyographic, biomechanical & histological analyses | Positive: Larger load to failure and less fat infiltration |
Chen et al. | In-vivo | Murine | Acute full | ADSC imbedded in fibrin sealant scaffold | Biomechanical & histological analyses | Positive: Better biomechanical strength and histological score |
Choi et al. | In-vivo | Rat | Chronic full | ADSC sheets interposed at the enthesis | Biomechanical & histological analyses | Positive: Successful complete regeneration and biomechanical strength |
Valencia Mora et al. | In-vivo | Rat | Chronic full | ADSC, ADSC + TGF-β3 | Biomechanical & histological analyses | Positive: Reduced inflammation |
Negative: Unchanged maximum load, elastic energy, mechanical deformation, and stiffness |
Table 1. Summary of cell-based therapies literature findings
Author | Study | Model | Tear | Intervention | Outcome measure | Results |
---|---|---|---|---|---|---|
Honda et al. | In-vivo | Rabbit | Chronic full | MSC + HA | Biomechanical, histological, and immunohistochemical analyses | Positive: Improved ultimate load and faster healing |
Jo et al. | Clinical | Human | Chronic full | BMSC + arthroscopic repeated channeling | Pain scale, ROM, muscle strength, patient satisfaction questionnaire, and functional scores. Structural integrity by MRI and CT | Positive: Enhanced structural integrity of the repair and decreased retears |
Hernigou et al. | Clinical | Human | Chronic partial | BMSC + arthroscopy | MRI | Positive: Faster complete healing/retear prevention |
Taniguchi et al. | Clinical | Human | Chronic partial | ASH + BMSC | MRI | Positive: Reduced retear rates/better integrity |
Han et al. | In-vitro, in-vivo | Rat | Acute full | PRP-infused BMSC | Expression of genes that related to tissue repair, bone formation, and tendon regeneration; | Positive: Stronger signals to angiogenesis, bone formation, and tendon generation in-situ |
Biomechanical assessment | Promoted healing in-vivo | |||||
Gulotta et al. | In-vivo | Rat | Acute full | BMSC | Biomechanical & histological analyses | Negative: No change in structure, composition, or strength |
Gulotta et al. | In-vivo | Rat | Acute full | MT1-MMP-transduced MSCs | Biomechanical & histological analyses | Positive: Better fibrocartilage formation, higher ultimate load and stress to failure, and higher stiffness |
Oh et al. | In-vivo | Rabbit | Chronic full | ADSC + suture | Electromyographic, biomechanical & histological analyses | Positive: Larger load to failure and less fat infiltration |
Chen et al. | In-vivo | Murine | Acute full | ADSC imbedded in fibrin sealant scaffold | Biomechanical & histological analyses | Positive: Better biomechanical strength and histological score |
Choi et al. | In-vivo | Rat | Chronic full | ADSC sheets interposed at the enthesis | Biomechanical & histological analyses | Positive: Successful complete regeneration and biomechanical strength |
Valencia Mora et al. | In-vivo | Rat | Chronic full | ADSC, ADSC + TGF-β3 | Biomechanical & histological analyses | Positive: Reduced inflammation |
Negative: Unchanged maximum load, elastic energy, mechanical deformation, and stiffness |
Author | Study | Model | Tear | Intervention | Outcome measure | Study results |
---|---|---|---|---|---|---|
Zong et al. | In-vivo | Rat | Acute full | Ihh + MSC | Immunohistochemical staining and proliferating cell nuclear antigen staining | Positive: Increased Gli1 and Patched1 expression. More organised and stronger staining for collagen II |
Schwartz et al. | In-vivo | Murine | Acute partial | Ihh | Lineage tracing | Positive: Gli1 lineage cells that originate in utero eventually populate the entire mature enthesis. Ablation of the Hh-responsive cells during the first week of postnatal development resulted in a loss of mineralised fibrocartilage |
Schwartz et al. | In-vivo | Mouse | Acute partial | Ihh | Lineage tracing | Positive: High levels of Gli1 expression in immature mice and mature entheses had fewer Gli1+ cells |
Hettrich et al. | In-vivo | Rat | Acute full | Systemic PTH | Histologic, immunohistochemical, biomechanical analyses | Positive: Higher stiffness, bone volume and mineral content; More fibrocartilage, osteoblasts, and blood vessels formation; Better collagen orientation |
Duchman et al. | In-vivo | Rat | Acute full | Systemic rhPTH | Biomechanical and histologic analysis | Positive: Higher load to failure. Expression of intracellular and extracellular VEGF |
Oh et al. | Clinical | Human | Chronic full | Systemic rhPTH | MRI, ROM, American Shoulder and Elbow Surgeons and Constant scores, and simple shoulder test | Positive: Lower retear rate |
Table 2. Summary of signaling molecules therapies literature findings
Author | Study | Model | Tear | Intervention | Outcome measure | Study results |
---|---|---|---|---|---|---|
Zong et al. | In-vivo | Rat | Acute full | Ihh + MSC | Immunohistochemical staining and proliferating cell nuclear antigen staining | Positive: Increased Gli1 and Patched1 expression. More organised and stronger staining for collagen II |
Schwartz et al. | In-vivo | Murine | Acute partial | Ihh | Lineage tracing | Positive: Gli1 lineage cells that originate in utero eventually populate the entire mature enthesis. Ablation of the Hh-responsive cells during the first week of postnatal development resulted in a loss of mineralised fibrocartilage |
Schwartz et al. | In-vivo | Mouse | Acute partial | Ihh | Lineage tracing | Positive: High levels of Gli1 expression in immature mice and mature entheses had fewer Gli1+ cells |
Hettrich et al. | In-vivo | Rat | Acute full | Systemic PTH | Histologic, immunohistochemical, biomechanical analyses | Positive: Higher stiffness, bone volume and mineral content; More fibrocartilage, osteoblasts, and blood vessels formation; Better collagen orientation |
Duchman et al. | In-vivo | Rat | Acute full | Systemic rhPTH | Biomechanical and histologic analysis | Positive: Higher load to failure. Expression of intracellular and extracellular VEGF |
Oh et al. | Clinical | Human | Chronic full | Systemic rhPTH | MRI, ROM, American Shoulder and Elbow Surgeons and Constant scores, and simple shoulder test | Positive: Lower retear rate |
Author | Study | Model | Tear | Intervention | Outcome measure | Study results |
---|---|---|---|---|---|---|
Würgler-Hauri et al. | In-vivo | Rat | Acute full | BMP-12-14, bFGF, COMP, CTGF, PDGFB, TGF-β1 | Immunohistochemical staining | Positive: Increase in the expression of all GFs at 1 week, and followed by a return to control or undetectable levels by 16 weeks |
Kobayashi et al. | In-vivo | Rabbit | Acute full | BMP-12-14, bFGF, COMP, CTGF, PDGFB, TGF-β1 | Light microscopy after staining with hematoxylin-eosin and Elastica-Masson; Immunohistochemical staining | Positive: GFs are involved in early phases of healing promotion |
Rodeo et al. | In-vivo | Sheep | Acute full | BMP and VEGF | MRI, plain radiographs, histologic analysis, and biomechanical testing | Positive: Greater formation of new bone, fibrocartilage, and soft tissue, with an increase in tendon attachment strength |
Angeline and Rodeo | In-vivo | Sheep | Acute full | BMP and VEGF | Histologic analysis | Positive: Induced angiogenesis and vasculogenesis. Faster and better recovery |
Manning et al. | In-vivo | Rat | Acute full | TGF-β3 | Histologic and biomechanical analyses | Negative: Disorganised scar and inferior mechanical properties |
Kim et al. | In-vivo | Rat | Acute full | TGF-β3 | Histologic and biomechanical analyses | Negative: Disorganised scar and inferior mechanical properties |
Davies et al. | In-vivo | Mouse | Acute full | Inhibiting TGF-β1 | Histologic analysis | Positive: Reduced fibrosis, fatty infiltration, and muscle atrophy |
Jensen et al. | In-vivo | Mouse | Acute full and partial | TGF-β3 + cytokine + MMP inhibitors | Reviewing the literature | Positive: Enhanced healing |
Zhou et al. | In-vivo | Rat | Acute full | rhFGF-18 | Histologic analysis | Positive: Promoted chondrogenesis and promoted healing and regeneration |
Sitcheran et al. | In-vivo | Mouse | Acute full | TGF-β3 | Histologic analysis | Negative: No improvement in healing |
Gulotta et al. | In-vivo | Rat | Acute and chronic full | TNF inhibitor | Histologic and biomechanical analyses | Positive: Elevated fibrocartilage, and enhanced load to failure and stiffness |
Dorman et al. | In-vivo | Mouse | Acute full | BMP-2-7 | Histologic analysis | Positive: Fully healed enthesis without toxicity |
Kabuto et al. | In-vivo | Rat | Acute full | BMP-2-7 | Histologic and biomechanical analyses | Positive: Improved biomechanical properties |
Table 3. Summary of growth factor-based therapies literature findings
Author | Study | Model | Tear | Intervention | Outcome measure | Study results |
---|---|---|---|---|---|---|
Würgler-Hauri et al. | In-vivo | Rat | Acute full | BMP-12-14, bFGF, COMP, CTGF, PDGFB, TGF-β1 | Immunohistochemical staining | Positive: Increase in the expression of all GFs at 1 week, and followed by a return to control or undetectable levels by 16 weeks |
Kobayashi et al. | In-vivo | Rabbit | Acute full | BMP-12-14, bFGF, COMP, CTGF, PDGFB, TGF-β1 | Light microscopy after staining with hematoxylin-eosin and Elastica-Masson; Immunohistochemical staining | Positive: GFs are involved in early phases of healing promotion |
Rodeo et al. | In-vivo | Sheep | Acute full | BMP and VEGF | MRI, plain radiographs, histologic analysis, and biomechanical testing | Positive: Greater formation of new bone, fibrocartilage, and soft tissue, with an increase in tendon attachment strength |
Angeline and Rodeo | In-vivo | Sheep | Acute full | BMP and VEGF | Histologic analysis | Positive: Induced angiogenesis and vasculogenesis. Faster and better recovery |
Manning et al. | In-vivo | Rat | Acute full | TGF-β3 | Histologic and biomechanical analyses | Negative: Disorganised scar and inferior mechanical properties |
Kim et al. | In-vivo | Rat | Acute full | TGF-β3 | Histologic and biomechanical analyses | Negative: Disorganised scar and inferior mechanical properties |
Davies et al. | In-vivo | Mouse | Acute full | Inhibiting TGF-β1 | Histologic analysis | Positive: Reduced fibrosis, fatty infiltration, and muscle atrophy |
Jensen et al. | In-vivo | Mouse | Acute full and partial | TGF-β3 + cytokine + MMP inhibitors | Reviewing the literature | Positive: Enhanced healing |
Zhou et al. | In-vivo | Rat | Acute full | rhFGF-18 | Histologic analysis | Positive: Promoted chondrogenesis and promoted healing and regeneration |
Sitcheran et al. | In-vivo | Mouse | Acute full | TGF-β3 | Histologic analysis | Negative: No improvement in healing |
Gulotta et al. | In-vivo | Rat | Acute and chronic full | TNF inhibitor | Histologic and biomechanical analyses | Positive: Elevated fibrocartilage, and enhanced load to failure and stiffness |
Dorman et al. | In-vivo | Mouse | Acute full | BMP-2-7 | Histologic analysis | Positive: Fully healed enthesis without toxicity |
Kabuto et al. | In-vivo | Rat | Acute full | BMP-2-7 | Histologic and biomechanical analyses | Positive: Improved biomechanical properties |
Author | Study | Model | Tear | Intervention | Outcome measure | Study results | ||
---|---|---|---|---|---|---|---|---|
Huang et al. | In-vivo | Rabbit | Acute full | KGN-loaded GelMA hydrogel + BMSC scaffold | Macroscopy, microcomputed tomography, histology, and biomechanical tests | Positive: Promoted fibrocartilage formation and superior mechanical properties | ||
Novakova et al. | In-vivo | Sheep | Acute full | Engineered tendon construct with BMSCs | X-ray and biomechanical tests | Positive: Native-like enthesis with higher modulus | ||
Han et al. | In-vivo | Rabbit | Acute full | BMP-2 + polyaspartic acid + Smad/RUNX2 signaling | Transmission electron microscopy staining; Biomechanics and histological assessment | Positive: Increased bone and tissue mineral density and ultimate load strength | ||
Ousema et al. | In-vitro | RC tear | 3D woven PCL scaffold + IL-1 inhibition on MSCs | Histological, biomechanical, and immunohistochemistry analyses | Positive: Mechanical functionality preserved with the use of a 3D woven PCL scaffold | |||
Jiang et al. | In-vitro | RC tear | 3D PLGA scaffold + a cell-laden collagen hydrogel + ADSCs | Histological and biomechanics analyses | Positive: Improvement in mechanical properties and biocompatibility | |||
Iannotti et al. | Clinical | Human | Chronic full | SIS | Penn shoulder-score questionnaire and MRI | Negative: No improvement in healing and clinical results | ||
Malcarney et al. | Clinical | Human | Chronic full | SIS | Study discontinued due to adverse effects | Negative: Inflammatory reaction | ||
Sclamberg et al. | Clinical | Human | Chronic full | SIS | Patient questionnaire, MRI, and ASES | Negative: No improvement and worse pot-operative outcomes | ||
Ciampi et al. | Clinical | Aging human | Chronic full | Polypropylene augmentation patch | Ultrasound, muscle strength, and VAS | Positive: Improved muscle strength, pain score, and tendon integrity | ||
Cai et al. | Clinical | Aging human | Chronic full | 3D biological collagen-I mesh | MRI, VAS, UCLA SST, and Constant score | Positive: Less retear rates | ||
Hoberman et al. | In-vitro | RC tear | DBM + BMSCs + PRP | Adhesion, proliferation, and differentiation assays | Positive: Better adhesion, proliferation, and differentiation | |||
Thangarajah et al. | In-vivo | Rat | Chronic full | DBM | Histological analysis | Negative: No improvement in collagen organisation and fibrocartilage formation | ||
Thangarajah et al. | In-vivo | Rat | Chronic full | DBM + MSCs | Histological analysis | Positive: Enhanced healing | ||
Smith et al. | In-vivo | Canine | Chronic full | PRP + DBM | Histological and biomechanical analysis | Positive: Improvement in strength and histological structure | ||
Wellington et al. | Clinical | Human | Chronic full | DBM + MSCs | MRI | Negative: Supraspinatus failure | ||
Chae et al. | In-vivo | Mouse | Chronic full | 3D cell-printed tendon-bone interface construct | >Gait analysis, histological and biomechanical analysis | Positive: Fully formed enthesis, improved shoulder outcome and biomechanical properties | ||
Yoon et al. | Clinical | Aging and young human | Chronic full | ADF | ROM, VAS, and MRI | Positive: No adverse effects, improved VAS, and functional scores | ||
Warth et al. | Clinical | Human | Chronic full | PRP | MRI and Constant score | Positive: Lower retear and improved constant score | ||
Castricini et al. | Clinical | Human | Chronic partial | Autologous PRFM | MRI | Positive: Improved tendon integrity | ||
Chronic full | Autologous PRFM | MRI | Negative: No difference in constant score and tendon integrity | |||||
Giovannetti de Sanctis et al. | Systematic review | Human | Chronic partial | PRP | Shoulder function and VAS | Positive: Improved pain and shoulder function | ||
Von Wehren et al. | Clinical | Human | Chronic partial | PRP | MRI, Constant score, ASES, shoulder ROM, and VAS | Positive: Improved pain and function | ||
Xu and Xue | Systematic review | Human | Chronic full | PRP | Retear rate, Constant, UCLA, ASES, VAS, and adverse effects | Positive: Improved shoulder outcome and reduced retear rate | ||
Rha et al. | Clinical | Human | Chronic partial | PRP | Shoulder Pain and Disability Index, ROM, and ultrasound | Positive: No adverse effects, and improved shoulder pain and function | ||
Shams et al. | Clinical | Human | Chronic partial | PRP | MRI, ASES, Constant Score, SST, and VAS | Positive: Improved shoulder function and minor MRI improvement | ||
Cai et al. | Clinical | Young human | Acute partial | SH + PRP | VAS, Constant score, and MRI | Positive: Better VAS, constant score, and MRI findings | ||
Ryan et al. | Systematic review | Human | Chronic full | PRP | Constant, ASES, UCLA, SST, VAS, and retear rate | Positive: Reduced retear rates and improved clinical outcomes | ||
Lavoie-Gagne et al. | Systematic review and meta-analysis | Human | Chronic full | PRP | Clinical characteristics, retear rates, ROM, and patient reported outcomes | Positive: Reduced retear rates and improved clinical outcomes | ||
Ilhanli et al. | Clinical | Human | Chronic partial | PRP | ROM, VAS, Disabilities of Arm, Shoulder and Hand questionnaire, Neer's, Hawkins' and drop arm tests and Beck Depression Inventory questionnaire | Negative: Results were not superior to physiotherapy |
Table 4. Summary of scaffold-based therapies literature findings
Author | Study | Model | Tear | Intervention | Outcome measure | Study results | ||
---|---|---|---|---|---|---|---|---|
Huang et al. | In-vivo | Rabbit | Acute full | KGN-loaded GelMA hydrogel + BMSC scaffold | Macroscopy, microcomputed tomography, histology, and biomechanical tests | Positive: Promoted fibrocartilage formation and superior mechanical properties | ||
Novakova et al. | In-vivo | Sheep | Acute full | Engineered tendon construct with BMSCs | X-ray and biomechanical tests | Positive: Native-like enthesis with higher modulus | ||
Han et al. | In-vivo | Rabbit | Acute full | BMP-2 + polyaspartic acid + Smad/RUNX2 signaling | Transmission electron microscopy staining; Biomechanics and histological assessment | Positive: Increased bone and tissue mineral density and ultimate load strength | ||
Ousema et al. | In-vitro | RC tear | 3D woven PCL scaffold + IL-1 inhibition on MSCs | Histological, biomechanical, and immunohistochemistry analyses | Positive: Mechanical functionality preserved with the use of a 3D woven PCL scaffold | |||
Jiang et al. | In-vitro | RC tear | 3D PLGA scaffold + a cell-laden collagen hydrogel + ADSCs | Histological and biomechanics analyses | Positive: Improvement in mechanical properties and biocompatibility | |||
Iannotti et al. | Clinical | Human | Chronic full | SIS | Penn shoulder-score questionnaire and MRI | Negative: No improvement in healing and clinical results | ||
Malcarney et al. | Clinical | Human | Chronic full | SIS | Study discontinued due to adverse effects | Negative: Inflammatory reaction | ||
Sclamberg et al. | Clinical | Human | Chronic full | SIS | Patient questionnaire, MRI, and ASES | Negative: No improvement and worse pot-operative outcomes | ||
Ciampi et al. | Clinical | Aging human | Chronic full | Polypropylene augmentation patch | Ultrasound, muscle strength, and VAS | Positive: Improved muscle strength, pain score, and tendon integrity | ||
Cai et al. | Clinical | Aging human | Chronic full | 3D biological collagen-I mesh | MRI, VAS, UCLA SST, and Constant score | Positive: Less retear rates | ||
Hoberman et al. | In-vitro | RC tear | DBM + BMSCs + PRP | Adhesion, proliferation, and differentiation assays | Positive: Better adhesion, proliferation, and differentiation | |||
Thangarajah et al. | In-vivo | Rat | Chronic full | DBM | Histological analysis | Negative: No improvement in collagen organisation and fibrocartilage formation | ||
Thangarajah et al. | In-vivo | Rat | Chronic full | DBM + MSCs | Histological analysis | Positive: Enhanced healing | ||
Smith et al. | In-vivo | Canine | Chronic full | PRP + DBM | Histological and biomechanical analysis | Positive: Improvement in strength and histological structure | ||
Wellington et al. | Clinical | Human | Chronic full | DBM + MSCs | MRI | Negative: Supraspinatus failure | ||
Chae et al. | In-vivo | Mouse | Chronic full | 3D cell-printed tendon-bone interface construct | >Gait analysis, histological and biomechanical analysis | Positive: Fully formed enthesis, improved shoulder outcome and biomechanical properties | ||
Yoon et al. | Clinical | Aging and young human | Chronic full | ADF | ROM, VAS, and MRI | Positive: No adverse effects, improved VAS, and functional scores | ||
Warth et al. | Clinical | Human | Chronic full | PRP | MRI and Constant score | Positive: Lower retear and improved constant score | ||
Castricini et al. | Clinical | Human | Chronic partial | Autologous PRFM | MRI | Positive: Improved tendon integrity | ||
Chronic full | Autologous PRFM | MRI | Negative: No difference in constant score and tendon integrity | |||||
Giovannetti de Sanctis et al. | Systematic review | Human | Chronic partial | PRP | Shoulder function and VAS | Positive: Improved pain and shoulder function | ||
Von Wehren et al. | Clinical | Human | Chronic partial | PRP | MRI, Constant score, ASES, shoulder ROM, and VAS | Positive: Improved pain and function | ||
Xu and Xue | Systematic review | Human | Chronic full | PRP | Retear rate, Constant, UCLA, ASES, VAS, and adverse effects | Positive: Improved shoulder outcome and reduced retear rate | ||
Rha et al. | Clinical | Human | Chronic partial | PRP | Shoulder Pain and Disability Index, ROM, and ultrasound | Positive: No adverse effects, and improved shoulder pain and function | ||
Shams et al. | Clinical | Human | Chronic partial | PRP | MRI, ASES, Constant Score, SST, and VAS | Positive: Improved shoulder function and minor MRI improvement | ||
Cai et al. | Clinical | Young human | Acute partial | SH + PRP | VAS, Constant score, and MRI | Positive: Better VAS, constant score, and MRI findings | ||
Ryan et al. | Systematic review | Human | Chronic full | PRP | Constant, ASES, UCLA, SST, VAS, and retear rate | Positive: Reduced retear rates and improved clinical outcomes | ||
Lavoie-Gagne et al. | Systematic review and meta-analysis | Human | Chronic full | PRP | Clinical characteristics, retear rates, ROM, and patient reported outcomes | Positive: Reduced retear rates and improved clinical outcomes | ||
Ilhanli et al. | Clinical | Human | Chronic partial | PRP | ROM, VAS, Disabilities of Arm, Shoulder and Hand questionnaire, Neer's, Hawkins' and drop arm tests and Beck Depression Inventory questionnaire | Negative: Results were not superior to physiotherapy |
Figure 2. Categorised literature findings: stem cells, GFs, and scaffolds vary in effect depending on the extent of the tear, chronicity level, population, and their combinations. Majority of studies investigated acute full tears, while less studies were investigating partial and full chronic tears. Very few studies considered the age of the studied population. 3D: three-dimensional; ADF: autologous dermal fibroblast; ADSC: adipose-derived stem cell; bFGF: basic fibroblast growth factor; BMP: bone morphogenetic protein; BMSC: bone marrow mesenchymal stem cell; COMP: cartilage oligomeric matrix protein; CTGF: connective tissue growth factor; DBM: demineralised bone matrix; GelMA: gelatin methacrylol; GF: growth factor; HA: hyaluronic acid; Ihh: Indian hedgehog; KGN: kartogenin; MMP: matrix metalloproteinase; MSC: mesenchymal stem cell; PCL: polycaprolactone; PDGFB: platelet-derived growth factor-B; PLGA: polylactide-co-glycolide acid; PRFM: platelet-rich fibrin clot matrix; PRP: platelet-rich plasma; PTH: parathyroid hormone; SH: sodium hyaluronate; SIS: small intestine submucosa; TGF: transforming growth factor; TNF: tumour necrosis factor.
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