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The ability to monitor, in real time, the mechanical forces on tendons after surgical repair could allow personalised rehabilitation programs to be developed for recovering patients. However, the development of devices capable of such measurements has been hindered by the strict requirements of biocompatible materials and the need for sensors with satisfactory performance. Here we report an implantable pressure and strain sensor made entirely of biodegradable materials. The sensor is designed to degrade after its useful lifetime, eliminating the need for a second surgery to remove the device. It can measure strain and pressure independently using two vertically isolated sensors capable of discriminating strain as small as 0.4% and the pressure exerted by a grain of salt (12 Pa) without interfering with one another. The device has minimal hysteresis, a response time in the millisecond range, and an excellent cycling stability for strain and pressure sensing, respectively. We have incorporated a biodegradable elastomer which was optimized to improve the strain cycling performances by 54%. An in vivo study shows that the sensor exhibits excellent biocompatibility and function in a rat model, illustrating the potential applicability of the device to the real-time monitoring of tendon healing. Text body In the U.S. alone, around 14 million people per year suffer from tendon, ligament, and joint injuries 1. After injury, tissues in the body undergo changes in their native biomechanical properties in order to repairs themselves. This is true for both hard tissues (bones) and soft tissues (tendons, skin, muscles). The objective of surgery and rehabilitation is to restore the tissues to their pre-injury function, with biomechanical properties as close as possible to native properties 2. A diagnostic tool that measures the biomechanical properties of the repair site in real-time would represent a significant step towards improved assessment of healing and the development of personalized rehabilitation strategies 3. Current clinical practice for monitoring tissue rehabilitation includes magnetic resonance imaging (MRI) or ultrasound, which provide a snapshot of tissue density and inflammation 4. Implantable sensors could give continuous information about tissue strain during rehabilitation protocols, as well as during the patient's daily activities, allowing activities to be tailored based on what the tissue can tolerate. Previously described implantable sensors have limited biocompatibility or have been designed for laboratory biomechanics studies rather than clinical practice 4,5 .

BackgroundAlthough autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit.MethodsWe developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer. Twelve adult male rats with immune deficiency underwent mid-thigh-level transection of the right sciatic nerve. The resulting 5-mm nerve gap was bridged using 8-mm Bio 3D conduits (Bio 3D group, n = 6) and silicone tube (silicone group, n = 6). Several assessments were conducted to examine nerve regeneration eight weeks post-surgery.ResultsKinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01). Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01). Histological and morphological studies revealed neural cell expression in all regions of the regenerated nerves and the presence of many well-myelinated axons in the Bio 3D group. The wet muscle weight of the tibialis anterior muscle was significantly higher in the Bio 3D group than the silicone group (0.544 ± 0.063 versus 0.396 ± 0.031, respectively; p < 0.01).ConclusionsWe confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model.

Cells, scaffolds, growth factors, and vascularity are essential for nerve regeneration. Previously, we reported that the insertion of a vascular bundle and the implantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) into a nerve conduit promoted peripheral nerve regeneration. In this study, the efficacy of nerve conduits containing a vascular bundle, BM-MSCs, and thermally decellularized allogenic nerve matrix (DANM) was investigated using a rat sciatic nerve model with a 20-mm defect. Lewis rats were used as the sciatic nerve model and for the preparation of BM-MSCs, and Dark Agouti rats were used for the preparation of the DANM. The revascularization and the immunogenicity of the DANM were investigated histologically. The regeneration of nerves through nerve conduits containing vessels, BM-MSCs, and DANM (VBD group) was evaluated based on electrophysiological, morphometric, and reinnervated muscle weight measurements and compared with that of vessel-containing conduits that were implanted with BM-MSCs (VB group). The DANM that was implanted into vessel-containing tubes (VCTs) was revascularized by neovascular vessels that originated from the inserted vascular bundle 5-7 days after surgery. The number of CD8 + cells found in the DANM in the VCT was significantly smaller than that detected in the untreated allogenic nerve segment. The regenerated nerve in the VBD group was significantly superior to that in the VB group with regard to the amplitude of the compound muscle action potential detected in the pedal adductor muscle; the number, diameter, and myelin thickness of the myelinated axons; and the tibialis anterior muscle weight at 12 and 24 weeks. The additional implantation of the DANM into the BM-MSC-implanted VCT optimized the axonal regeneration through the conduit. Nerve conduits constructed with vascularity, cells, and scaffolds could be an effective strategy for the treatment of peripheral nerve injuries with significant segmental defects.

Rotator cuff (RTC) repair outcomes are unsatisfactory due to the poor healing capacity of the tendon bone interface (TBI). In our preceding study, tendon hydrogel (tHG), which is a type I collagen rich gel derived from human tendons, improved biomechanical properties of the TBI in a rat chronic RTC injury model. Here we investigated whether adipose‐derived stem cell (ASC)‐seeded tHG injection at the repair site would further improve RTC healing. Rats underwent bilateral supraspinatus tendon detachment. Eight weeks later injured supraspinatus tendons were repaired with one of four treatments. In the control group, standard transosseous suture repair was performed. In the ASC, tHG, tHGASC groups, ASC in media, tHG, and ASC‐seeded tHG were injected at repair site after transosseous suture repair, respectively. Eight weeks after repair, the TBI was evaluated biomechanically, histologically, and via micro CT. Implanted ASCs were detected in ASC and tHGASC groups 7 weeks after implantation. ACS implantation improved bone morphometry at the supraspinatus insertion on the humerus. Injection of tHG improved biomechanical properties of the repaired TBI. RTC healing in tHGASC group was significantly better than control but statistically equivalent to the tHG group based on biomechanical properties, fibrocartilage area at the TBI, and bone morphometry at the supraspinatus insertion. In a rat RTC chronic injury model, no biomechanical advantage was gained with ASC augmentation of tHG. Clinical Significance: Tendon hydrogel augmentation with adipose derived stem cells does not significantly improve TBI healing over tHG alone in a chronic rotator cuff injury model. © 2019 Orthopaedic Research Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.