Biodegradable Piezoelectric Force Sensor.

Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery that can damage directly interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which only relies on safe medical materials and requires no complex fabrication process to provide accurate information on important biophysiological forces. Here, we present a strategy for material processing, electromechanical analysis, device fabrication, and assessment of a piezoelectric Poly-l-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force sensor, which only employs medical materials used commonly in Food and Drug Administration-approved implants, for the monitoring of biological forces. We show the sensor can precisely measure pressures in a wide range of 0-18 kPa and sustain a reliable performance for a period of 4 d in an aqueous environment. We also demonstrate this PLLA piezoelectric sensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction. This piezoelectric sensor offers an appealing alternative to present biodegradable electronic devices for the monitoring of intraorgan pressures. The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices.

Highly piezoelectric, biodegradable, and flexible amino acid nanofibers for medical applications.

Amino acid crystals are an attractive piezoelectric material as they have an ultrahigh piezoelectric coefficient and have an appealing safety profile for medical implant applications. Unfortunately, solvent-cast films made from glycine crystals are brittle, quickly dissolve in body fluid, and lack crystal orientation control, reducing the overall piezoelectric effect. Here, we present a material processing strategy to create biodegradable, flexible, and piezoelectric nanofibers of glycine crystals embedded inside polycaprolactone (PCL). The glycine-PCL nanofiber film exhibits stable piezoelectric performance with a high ultrasound output of 334 kPa [under 0.15 voltage root-mean-square (Vrms)], which outperforms the state-of-the-art biodegradable transducers. We use this material to fabricate a biodegradable ultrasound transducer for facilitating the delivery of chemotherapeutic drug to the brain. The device remarkably enhances the animal survival time (twofold) in mice-bearing orthotopic glioblastoma models. The piezoelectric glycine-PCL presented here could offer an excellent platform not only for glioblastoma therapy but also for developing medical implantation fields.

Jaw bite force measurement device.

We describe a cost-effective device that uses an off-the-shelf force transducer to measure patient bite force as a diagnostic aid in determining dental implant size, number of implants, and prosthetic design for restoring partial edentulism. The main advantages of the device are its accuracy, simplicity, modularity, ease of manufacturing, and low cost.

Improved inter-residue contact prediction via a hybrid generative model and dynamic loss function.

Protein contact maps represent spatial pairwise inter-residue interactions, providing a protein's translationally and rotationally invariant topological representation. Accurate contact map prediction has been a critical driving force for improving protein structure determination. Contact maps can also be used as a stand-alone tool for varied applications such as prediction of protein-protein interactions, structure-aware thermal stability or physicochemical properties. We develop a novel hybrid contact map prediction model, CGAN-Cmap, that uses a generative adversarial neural network embedded with a series of modified squeeze and excitation residual networks. To exploit features of different dimensions, we introduce two parallel modules. This architecture improves the prediction by increasing receptive fields, surpassing redundant features and encouraging more meaningful ones from 1D and 2D inputs. We also introduce a new custom dynamic binary cross-entropy loss function to address the input imbalance problem for highly sparse long-range contacts in proteins with insufficient homologs. We evaluate the model's performance on CASP 11, 12, 13, 14, and CAMEO test sets. CGAN-Cmap outperforms state-of-the-art models, improving precision of medium and long-range contacts by at least 3.5%. As a direct assessment between our model and AlphaFold2, the leading available protein structure prediction model, we compare extracted contact maps from AlphaFold2 and predicted contact maps from CGAN-Cmap. The results show that CGAN-Cmap has a mean precision higher by 1% compared to AlphaFold2 for most ranges of contacts. These results demonstrate an efficient approach for highly accurate contact map prediction toward accurate characterization of protein structure, properties and functions from sequence.

Force and movement of non-osseointegrated implants: an in vitro study.

Dental implants have enabled a dramatic increase in the quality of life for many partially edentulous and edentulous patents. Immediate loading of newly placed dental implants is a recent advancement that attempts to meet patient demand. However, immediate loading of a just placed implant may induce implant failure to osseointegrate. Some patients can generate a biting force that can reach approximately 1300 Newtons (N) in the posterior jaws. The magnitude of bite force that would cause failure of osseointegration of newly placed implants is currently unknown. It has been proposed that osseointegration would fail if an implant is luxated in bone more than 50 to 150 microns. Fibrous tissue, not bone, would form. This study investigated the quantity of various off-axial forces required to move a nonosseointegrated 4.3 x 13 mm implant 50 microns. The previously published pilot study for this study found that the amount of horizontal force required to displace an implant 50 microns was approximately 150 N. This study found that the force needed to move the implants 100 microns at a horizontal approach, 0 degrees, averaged 50 N, with a range of 23-79 N; at 22 degrees, averaged 52 N, with a range of 27-70 N; and at 60 degrees averaged 87 N, with a range of 33-105 N.

Piezoelectric Biomaterials for Sensors and Actuators.

Recent advances in materials, manufacturing, biotechnology, and microelectromechanical systems (MEMS) have fostered many exciting biosensors and bioactuators that are based on biocompatible piezoelectric materials. These biodevices can be safely integrated with biological systems for applications such as sensing biological forces, stimulating tissue growth and healing, as well as diagnosing medical problems. Herein, the principles, applications, future opportunities, and challenges of piezoelectric biomaterials for medical uses are reviewed thoroughly. Modern piezoelectric biosensors/bioactuators are developed with new materials and advanced methods in microfabrication/encapsulation to avoid the toxicity of conventional lead-based piezoelectric materials. Intriguingly, some piezoelectric materials are biodegradable in nature, which eliminates the need for invasive implant extraction. Together, these advancements in the field of piezoelectric materials and microsystems can spark a new age in the field of medicine.

Measurement of the fatigue life of mini dental implants: a pilot study.

The fatigue life of mini or small-diameter dental implants is of particular interest because these implants are used to retain and support fixed and removable dental prostheses. The fatigue life of an implant depends on both the implant itself as well as on the physical properties of the bone. However, the capability to predict the fatigue life of a newly placed implant is currently inexistent. This pilot study represents the first step in developing such a methodology and focuses on the design of a cost-effective device to measure the fatigue life of a dental implant. In our measurements, the implant has been mounted in an essentially rigid support, but test specimens can also be bone mounted in vitro. Furthermore, we developed a finite element-based computer model capable of predicting the corresponding fatigue life. The finite element analysis was performed in ABAQUS, and the results predicted by the model correlated fairly well with our initial experimental results. Most of the 2-mm diameter implants fractured after more than a million cycles.

Force required to luxate a newly placed dental implant in bone: an in vitro pilot study.

Immediate loading of newly placed dental implants is a consideration when attempting to meet patients' demands. However, immediate loading may induce implant failure to osseointegrate, particularly in the case of a patient who can generate a biting force that can reach approximately 1300 Newtons (N) in the posterior jaws. The range of biting forces that prevent osseointegration of newly placed implants is currently unknown. However, it is suspected that osseointegration may fail if an implant is luxated in bone more than 50 microm, in which case fibrous tissue will be formed instead of bone. This pilot study was focused on finding the amount of horizontal off-axial force required to move a nonosseointegrated 4.3 x 13-mm implant 50 microm. The initial data show that the amount of horizontal force required to displace such an implant by 50 microm was on the order of 150 N. Assuming that the angle between the direction of the biting force and the vertical lies between 0 degrees and 20 degrees, our data show that a 4.3 x 13-mm implant may fail to osseointegrate for biting forces that are as low as 440 N. One implication of our study is that implants having smaller diameters may move and fail to osseointegrate for even lower biting forces.