Figure 4. Treatment of acute VML restores mass and force production.

(a) Schematic model of our VML treatment procedure using bioconstructs. TA muscles are isolated from donor mice (1). These muscles are used to obtain either: decellularized scaffolds, MuSCs, MRCs or ECM proteins to generate hydrogels (2). Scaffolds are reconstituted with isolated cells and hydrogel to generate bioconstructs (3). Bioconstructs are cultured in a bioreactor while the hydrogel cured, allowing media to perfuse across the bioconstructs (4). Once ready, bioconstructs are transplanted into VML injured TA muscles (5). (b) In vivo force production measurements of TA muscles treated with different bioconstructs following VML injury. After 30 days, the distal tendons were attached to a force transducer and contractions were induced through sciatic nerve stimulation (n=8). (c) Ex vivo force production measurements. The same muscles measured in b were then dissected and cultured in a chamber. The distal tendons were attached to a transducer and contractions were induced electrically in the culture bath (n=8). (d) The mass of each TA muscle was measured following ex vivo force measurements (n=6). In (b–d) average values of muscles that did not received VML injuries are labelled ‘uninjured’ and are indicated by a blue dotted line; average values of muscles that received a VML injury without any treatment are labelled ‘VML’ and are indicated by a red dotted line. Data are±s.e.m. For statistical analysis, t-tests were used. **P<0.001; ****P<0.00001, n.s.: not significant.