Modification of pore-wall in direct ink writing wollastonite scaffolds favorable for tuning biodegradation and mechanical stability and enhancing osteogenic capability.

Surface chemistry and mechanical stability determine the osteogenic capability of bone implants. The development of high-strength bioactive scaffolds for in-situ repair of large bone defects is challenging because of the lack of satisfying biomaterials. In this study, highly bioactive Ca-silicate (CSi) bioceramic scaffolds were fabricated by additive manufacturing and then modified for pore-wall reinforcement. Pure CSi scaffolds were fabricated using a direct ink writing technique, and the pore-wall was modified with 0%, 6%, or 10% Mg-doped CSi slurry (CSi, CSi-Mg6, or CSi-Mg10) through electrostatic interaction. Modified CSi@CSi-Mg6 and CSi@CSi-Mg10 scaffolds with over 60% porosity demonstrated an appreciable compressive strength beyond 20 MPa, which was ~2-fold higher than that of pure CSi scaffolds. CSi-Mg6 and CSi-Mg10 coating layers were specifically favorable for retarding bio-dissolution and mechanical decay of scaffolds in vitro. In-vivo investigation of critical-size femoral bone defects repair revealed that CSi@CSi-Mg6 and CSi@CSi-Mg10 scaffolds displayed limited biodegradation, accelerated new bone ingrowth (4-12 weeks), and elicited a suitable mechanical response. In contrast, CSi scaffolds exhibited fast biodegradation and retarded new bone regeneration after 8 weeks. Thus, tailoring of the chemical composition of pore-wall struts of CSi scaffolds is beneficial for enhancing the biomechanical properties and bone repair efficacy.

Fiber-Based Electret Nanogenerator with a Semisupported Structure for Wearable Electronics.

Fiber-based nanogenerators have great potential applications in wearable electronics such as portable nanodevices, e-skin, and artificial intelligence system. Here, we report a kind of fiber-based electret nanogenerator (FENG) with a semisupported core-shell structure. Owing to its unique structure, the open-circuit voltage and short-circuit current of the FENG reach 40 V and 0.6 µA, respectively, under a short working distance (∼25 µm). No obvious degradation of the output performance under a long-time continuous work (>16 h) and different humidity environments (20-95%) is observed, which demonstrates the FENG's good reliability and stability. Many universal materials, such as cotton rope, conductive sewing thread, and polyvinyl chloride tube, have been successfully used to fabricate FENG. Meanwhile, the FENG-based wearable fabric has been successfully developed to effectively harvest mechanical energy of human motion. The FENG is highly effective, reliable, and stable, promoting the development of fiber-based nanogenerators and their applications in self-powered wearable electronics.

Three-dimensional (3D) printed scaffold and material selection for bone repair.

Critical-sized bone defect repair remains a substantial challenge in clinical settings and requires bone grafts or bone substitute materials. However, existing biomaterials often do not meet the clinical requirements of structural support, osteoinductive property, and controllable biodegradability. To treat large-scale bone defects, the development of three-dimensional (3D) porous scaffolds has received considerable focus within bone engineering. A variety of biomaterials and manufacturing methods, including 3D printing, have emerged to fabricate patient-specific bioactive scaffolds that possess controlled micro-architectures for bridging bone defects in complex configurations. During the last decade, with the development of the 3D printing industry, a large number of tissue-engineered scaffolds have been created for preclinical and clinical applications using novel materials and innovative technologies. Thus, this review provides a brief overview of current progress in existing biomaterials and tissue engineering scaffolds prepared by 3D printing technologies, with an emphasis on the material selection, scaffold design optimization, and their preclinical and clinical applications in the repair of critical-sized bone defects. Furthermore, it will elaborate on the current limitations and potential future prospects of 3D printing technology. STATEMENT OF SIGNIFICANCE: 3D printing has emerged as a critical fabrication process for bone engineering due to its ability to control bulk geometry and internal structure of tissue scaffolds. The advancement of bioprinting methods and compatible ink materials for bone engineering have been a major focus to develop optimal 3D scaffolds for bone defect repair. Achieving a successful balance of cellular function, cellular viability, and mechanical integrity under load-bearing conditions is critical. Hybridization of natural and synthetic polymer-based materials is a promising approach to create novel tissue engineered scaffolds that combines the advantages of both materials and meets various requirements, including biological activity, mechanical strength, easy fabrication and controllable degradation. 3D printing is linked to the future of bone grafts to create on-demand patient-specific scaffolds.

Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats.

Peripheral nerve injury (PNI) is a major burden to society with limited therapeutic options, and novel biomaterials have great potential for shifting the current paradigm of treatment. With a rising prevalence of chronic illnesses such as diabetes mellitus (DM), treatment of PNI is further complicated, and only few studies have proposed therapies suitable for peripheral nerve regeneration in DM. To provide a supportive environment to restore structure and/or function of nerves in DM, we developed a novel thermo-sensitive heparin-poloxamer (HP) hydrogel co-delivered with basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) in diabetic rats with sciatic nerve crush injury. The delivery vehicle not only had a good affinity for large amounts of growth factors (GFs), but also controlled their release in a steady fashion, preventing degradation in vitro. In vivo, compared with HP hydrogel alone or direct GFs administration, GFs-HP hydrogel treatment is more effective at facilitating Schwann cell (SC) proliferation, leading to an increased expression of nerve associated structural proteins, enhanced axonal regeneration and remyelination, and improved recovery of motor function (all p < 0.05). Our mechanistic investigation also revealed that these neuroprotective and neuroregenerative effects of the GFs-HP hydrogel may be associated with activations of phosphatidylinositol 3 kinase and protein kinase B (PI3K/Akt), janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways. Our work provides a promising therapy option for peripheral nerve regeneration in patients with DM.

Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair.

Proper selection and effective delivery of combination drugs targeting multiple pathophysiological pathways key to spinal cord injury (SCI) hold promise to address the thus far scarce clinical therapeutics for improving recovery after SCI. In this study, we aim to develop a clinically feasible way for targeted delivery of multiple drugs with different physiochemical properties to the SCI site, detail the underlying mechanism of neural recovery, and detect any synergistic effect related to combination therapy. Methods: Liposomes (LIP) modified with a scar-targeted tetrapeptide (cysteine-alanine-glutamine-lysine, CAQK) were first constructed to simultaneously encapsulate docetaxel (DTX) and brain-derived neurotrophic factor (BDNF) and then were further added into a thermosensitive heparin-modified poloxamer hydrogel (HP) with affinity-bound acidic fibroblast growth factor (aFGF-HP) for local administration into the SCI site (CAQK-LIP-GFs/DTX@HP) in a rat model. In vivo fluorescence imaging was used to examine the specificity of CAQK-LIP-GFs/DTX binding to the injured site. Multiple comprehensive evaluations including biotin dextran amine anterograde tracing and magnetic resonance imaging were used to detect any synergistic effects and the underlying mechanisms of CAQK-LIP-GFs/DTX@HP both in vivo (rat SCI model) and in vitro (primary neuron). Results: The multiple drugs were effectively delivered to the injured site. The combined application of GFs and DTX supported neuro-regeneration by improving neuronal survival and plasticity, rendering a more permissive extracellular matrix environment with improved regeneration potential. In addition, our combination therapy promoted axonal regeneration via moderation of microtubule function and mitochondrial transport along the regenerating axon. Conclusion: This novel multifunctional therapeutic strategy with a scar-homing delivery system may offer promising translational prospects for the clinical treatment of SCI.

Engineering anatomically shaped vascularized bone grafts with hASCs and 3D-printed PCL scaffolds.

The treatment of large craniomaxillofacial bone defects is clinically challenging due to the limited availability of transplantable autologous bone grafts and the complex geometry of the bones. The ability to regenerate new bone tissues that faithfully replicate the anatomy would revolutionize treatment options. Advances in the field of bone tissue engineering over the past few decades offer promising new treatment alternatives using biocompatible scaffold materials and autologous cells. This approach combined with recent advances in three-dimensional (3D) printing technologies may soon allow the generation of large, bioartificial bone grafts with custom, patient-specific architecture. In this study, we use a custom-built 3D printer to develop anatomically shaped polycaprolactone (PCL) scaffolds with varying internal porosities. These scaffolds are assessed for their ability to support induction of human adipose-derived stem cells (hASCs) to form vasculature and bone, two essential components of functional bone tissue. The development of functional tissues is assessed in vitro and in vivo. Finally, we demonstrate the ability to print large mandibular and maxillary bone scaffolds that replicate fine details extracted from patient's computed tomography scans. The findings of this study illustrate the capabilities and potential of 3D printed scaffolds to be used for engineering autologous, anatomically shaped, vascularized bone grafts.

Designing tyrosine-derived polycarbonate polymers for biodegradable regenerative type neural interface capable of neural recording.

Next-generation neuroprosthetic limbs will require a reliable long-term neural interface to residual nerves in the peripheral nervous system (PNS). To this end, we have developed novel biocompatible materials and a fabrication technique to create high site-count microelectrodes for stimulating and recording from regenerated peripheral nerves. Our electrodes are based on a biodegradable tyrosine-derived polycarbonate polymer system with suitable degradation and erosion properties and a fabrication technique for deployment of the polymer in a porous, degradable, regenerative, multiluminal, multielectrode conduit. The in vitro properties of the polymer and the electrode were tuned to retain mechanical strength for over 24 days and to completely degrade and erode within 220 days. The fabrication technique resulted in a multiluminal conduit with at least 10 functioning electrodes maintaining recording site impedance in the single-digit kOhm range. Additionally, in vivo results showed that neural signals could be recorded from these devices starting at four weeks postimplantation and that signal strength increased over time. We conclude that our biodegradable regenerative-type neural interface is a good candidate for chronic high fidelity recording electrodes for integration with regenerated peripheral nerves.