Platelet-rich plasma promotes skeletal muscle regeneration and neuromuscular functional reconstitution in a concentration-dependent manner in a rat laceration model.

Abnormal function of injured muscle with innervation loss is a challenge in sports medicine. The difficulty of rehabilitation is regenerating and reconstructing the skeletal muscle tissue and the neuromuscular junction (NMJ). Platelet-rich plasma (PRP) releases various growth factors that may provide an appropriate niche for tissue regeneration. However, the specific mechanism of the PRP's efficacy on muscle healing remains unknown. In this study, we injected PRP with different concentration gradients (800, 1200, 1600 × 109 pl/L) or saline into a rat gastrocnemius laceration model. The results of histopathology and neuromyography show that PRP improved myofibers regeneration, facilitated electrophysiological recovery, and reduced fibrosis in a concentration-dependent manner. Furthermore, we found that PRP promotes the activity of satellite cells by upregulating the expression of the myogenic regulatory factor (MyoD, myogenin). Meanwhile, PRP promotes the regeneration and maturation of acetylcholine receptor (AChR) clusters of the Neuromuscular junction (NMJ) on the regenerative myofibers. Finally, we found that the expression of the Agrin, LRP4, and MuSK was upregulated in the PRP-treated groups, which may contribute to AChR cluster regeneration and functional recovery. The conclusions proposed a hypothesis for PRP treatment's efficacy and mechanism in muscle injuries, indicating promising application prospects.

In vivo evaluation of osseointegration ability of sintered bionic trabecular porous titanium alloy as artificial hip prosthesis.

Hydroxyapatite (HA) coatings have been widely used for improving the bone-implant interface (BII) bonding of the artificial joint prostheses. However, the incidence of prosthetic revisions due to aseptic loosening remains high. Porous materials, including three-dimensional (3D) printing, can reduce the elastic modulus and improve osseointegration at the BII. In our previous study, we identified a porous material with a sintered bionic trabecular structure with in vitro and in vivo bio-safety as well as in vivo mechanical safety. This study aimed to compare the difference in osseointegration ability of the different porous materials and HA-coated titanium alloy in the BII. We fabricated sintered bionic trabecular porous titanium acetabular cups, 3D-printed porous titanium acetabular cups, and HA-coated titanium alloy acetabular cups for producing a hip prosthesis suitable for beagle dogs. Subsequently, the imaging and histomorphological analysis of the three materials under mechanical loading in animals was performed (at months 1, 3, and 6). The results suggested that both sintered bionic porous titanium alloy and 3D-printed titanium alloy exhibited superior performances in promoting osseointegration at the BII than the HA-coated titanium alloy. In particular, the sintered bionic porous titanium alloy exhibited a favorable bone ingrowth performance at an early stage (month 1). A comparison of the two porous titanium alloys suggested that the sintered bionic porous titanium alloys exhibit superior bone in growth properties and osseointegration ability. Overall, our findings provide an experimental basis for the clinical application of sintered bionic trabecular porous titanium alloys.

Microfracture Augmentation With Direct In Situ Radial Shockwave Stimulation With Appropriate Energy Has Comparable Repair Performance With Tissue Engineering in the Porcine Osteochondral Defect Model.

BACKGROUND: The first-line clinical strategy for small cartilage/osteochondral defects is microfracture (MF). However, its repair efficacy needs improvement. HYPOTHESIS: Appropriate energy radial shockwave stimulation in MF holes would greatly improve repair efficacy in the porcine osteochondral defect model, and it may obtain comparable performance with common tissue engineering techniques. STUDY DESIGN: Controlled laboratory study. METHODS: Osteochondral defect models (8-mm diameter, 3-mm depth) were established in the weightbearing area of Bama pigs' medial femoral condyles. In total, 25 minipigs were randomly divided into 5 groups: control (Con; without treatment), MF, MF augmentation (MF+; treated with appropriate energy radial shockwave stimulation in MF holes after MF), tissue engineering (TE; treated with compounds of microcarrier and bone marrow mesenchymal stem cells), and sham (as the positive control). After 3 months of intervention, osteochondral specimens were harvested for macroscopic, radiological, biomechanical, and histological evaluations. The statistical data were analyzed using 1-way analysis of variance. RESULTS: Based on the macroscopic appearance, the smoothness and integration of the repaired tissue in the MF+ group were improved when compared with the Con and MF groups. The histological staining suggested more abundant cartilaginous matrix deposition in the MF+ group versus the Con and MF groups. The general scores of the macroscopic and histological appearances were comparable in the MF+ and the TE groups. The high signal areas of the osteochondral unit in the magnetic resonance images were significantly decreased in the MF+ group, with no difference with the TE group. The micro-computed tomography data demonstrated the safety of direct in situ radial shockwave performance. Biomechanical tests revealed that the repaired tissue's Young modulus was highest in the MF+ group and not statistically different from that in the TE group. CONCLUSION: Direct in situ radial shockwave stimulation with appropriate energy significantly improves the short-term repair efficacy of MF. More encouragingly, the MF+ group in our study obtained repair performance comparable with the TE therapy. CLINICAL RELEVANCE: This strategy is easy to perform and can readily be generalized with safety and higher cartilage repair efficacy. Moreover, it is expected to be accomplished under arthroscopy, indicating tremendous clinical transformative value.

Enhanced regeneration of bone defects using sintered porous Ti6Al4V scaffolds incorporated with mesenchymal stem cells and platelet-rich plasma.

A new highly controlled powder sintering technique was used for the fabrication of a porous Ti6Al4V scaffold. The platelet-rich plasma (PRP) was prepared using whole blood. The PRP was used as a cell carrier to inject bone marrow mesenchymal stem cells (MSC) into the pores of the Ti6Al4V scaffold in the presence of calcium chloride and thrombin, and then the composite construct of porous Ti6Al4V loaded with PRP gel and MSC was obtained. The bare Ti6Al4V scaffold and the Ti6Al4V scaffold loaded with MSC were used as controls. The characteristics and mechanical properties of the scaffold, and the biological properties of the constructs were evaluated by a series of in vitro and in vivo experiments. The results show that the sintered porous Ti6Al4V has good biocompatibility, and high porosity and large pore size, which can provide sufficient space and sufficient mechanical support for the growth of cells and bones without an obvious stress shielding effect. However, Ti6Al4V/MSC/PRP showed a significantly higher cell proliferation rate, faster bone growth speed, more bone ingrowth, and higher interfacial strength. Therefore, the porous Ti6Al4V scaffolds incorporated with MSC and PRP may be more effective at enhancing bone regeneration, and is expected to be used for bone defect repair.