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Minimally invasive approach to the repair of injured skeletal muscle with a shape-memory scaffold.

ABSTRACT: Repair of injured skeletal muscle by cell therapies has been limited by poor survival of injected cells. Use of a carrier scaffold delivering cells locally, may enhance in vivo cell survival, and promote skeletal muscle regeneration. Biomaterial scaffolds are often implanted into muscle tissue through invasive surgeries, which can result in trauma that delays healing. Minimally invasive approaches to scaffold implantation are thought to minimize these adverse effects. This hypothesis was addressed in the context of a severe mouse skeletal muscle injury model. A degradable, shape-memory alginate scaffold that was highly porous and compressible was delivered by minimally invasive surgical techniques to injured tibialis anterior muscle. The scaffold controlled was quickly rehydrated in situ with autologous myoblasts and growth factors (either insulin-like growth factor-1 (IGF-1) alone or IGF-1 with vascular endothelial growth factor (VEGF)). The implanted scaffolds delivering myoblasts and IGF-1 significantly reduced scar formation, enhanced cell engraftment, and improved muscle contractile function. The addition of VEGF to the scaffold further improved functional recovery likely through increased angiogenesis. Thus, the delivery of myoblasts and dual local release of VEGF and IGF-1 from degradable scaffolds implanted through a minimally invasive procedure effectively promoted the functional regeneration of injured skeletal muscle.

SUBMITTER: Wang L

PROVIDER: S-EPMC4435589 | biostudies-other | 2014 Aug

REPOSITORIES: biostudies-other

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Minimally invasive approach to the repair of injured skeletal muscle with a shape-memory scaffold.

Wang Lin L Cao Lan L Shansky Janet J Wang Zheng Z Mooney David D Vandenburgh Herman H

Molecular therapy : the journal of the American Society of Gene Therapy 20140428 8

Repair of injured skeletal muscle by cell therapies has been limited by poor survival of injected cells. Use of a carrier scaffold delivering cells locally, may enhance in vivo cell survival, and promote skeletal muscle regeneration. Biomaterial scaffolds are often implanted into muscle tissue through invasive surgeries, which can result in trauma that delays healing. Minimally invasive approaches to scaffold implantation are thought to minimize these adverse effects. This hypothesis was address ...[more]

PMID: 24769909

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Project description:This study's objectives were to test correlations among groups of biomarkers that are associated with condylar morphology and to apply artificial intelligence to test shape analysis features in a neural network (NN) to stage condylar morphology in temporomandibular joint osteoarthritis (TMJOA). Seventeen TMJOA patients (39.9 ± 11.7 y) experiencing signs and symptoms of the disease for less than 10 y and 17 age- and sex-matched control subjects (39.4 ± 15.2 y) completed a questionnaire, had a temporomandibular joint clinical exam, had blood and saliva samples drawn, and had high-resolution cone beam computed tomography scans taken. Serum and salivary levels of 17 inflammatory biomarkers were quantified using protein microarrays. A NN was trained with 259 other condyles to detect and classify the stage of TMJOA and then compared to repeated clinical experts' classifications. Levels of the salivary biomarkers MMP-3, VE-cadherin, 6Ckine, and PAI-1 were correlated to each other in TMJOA patients and were significantly correlated with condylar morphological variability on the posterior surface of the condyle. In serum, VE-cadherin and VEGF were correlated with one another and with significant morphological variability on the anterior surface of the condyle, while MMP-3 and CXCL16 presented statistically significant associations with variability on the anterior surface, lateral pole, and superior-posterior surface of the condyle. The range of mouth opening variables were the clinical markers with the most significant associations with morphological variability at the medial and lateral condylar poles. The repeated clinician consensus classification had 97.8% agreement on degree of degeneration within 1 group difference. Predictive analytics of the NN's staging of TMJOA compared to the repeated clinicians' consensus revealed 73.5% and 91.2% accuracy. This study demonstrated significant correlations among variations in protein expression levels, clinical symptoms, and condylar surface morphology. The results suggest that 3-dimensional variability in TMJOA condylar morphology can be comprehensively phenotyped by the NN.

Dataset Information

Minimally invasive approach to the repair of injured skeletal muscle with a shape-memory scaffold.

Publications

Minimally invasive approach to the repair of injured skeletal muscle with a shape-memory scaffold.

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