Physical cues like morphology, light, electric signal, mechanic signal, magnetic signal, and heat can be used as alternative regulators for expensive but short‐acting growth factors in bone tissue engineering to promote osteogenic differentiation and bone regeneration. As physical stimulation applied directly to the tissue cannot be focused on the bone defect area to regulate the cell behaviors and fate in situ, this limits the efficiency of precise bone regeneration. Biomaterials‐mediated in situ physical cues, as an effective strategy combining the synergistic effect of materials themselves, are put forward and studied widely to promote osteogenic differentiation and bone repair efficiently and precisely. Different types of physical cues provide different choices to better satisfy the requirements for targeted bone defect repair. In this review, the recent research about different biomaterials‐mediated physical cues accelerating osteogenesis in vitro and promoting in situ bone formation in vivo is introduced. Meanwhile, the corresponding possible mechanisms of various physical cues regulating cell responses are also discussed. This review provides useful and enlightening guidance for the utilization of intrinsically physical properties of functional materials to achieve efficient bone regeneration, leading to the design and construction of smart biomaterials for practical applications, and eventually promoting clinical translation.

Materials‐Mediated In Situ Physical Cues for Bone Regeneration

Advances in the use of calcium silicate-based materials in bone tissue engineering

Bioelectret poly(lactic acid) membranes with simultaneously enhanced physical interception and electrostatic adsorption of airborne PM0.3.

The osteogenic function of mesenchymal stem cells (MSCs) is mainly attributed to the paracrine effect of extracellular vesicles. MSC-derived exosomes are interesting candidates as biopharmaceuticals for drug delivery and for the engineering of biologically functionalized materials, and have emerged as cell-free regenerative medicine in recent years. In this study, bone marrow mesenchymal stem cell (BMSC)-derived exosomes were loaded with photothermal material layered black phosphorus (BP) modified poly(N-isopropylacrylamide) (PNIPAAm) thermosensitive hydrogels to explore their effects on bone defect repair. In vitro, it was confirmed that the local high heat of nano-BP irradiated using a near-infrared (NIR) laser could trigger the reversible cascade reaction of hydrogels, and that the mechanical contraction of hydrogels led to the controllable release of a large number of exosomes along with the release of water molecules. Furthermore, in vitro investigations demonstrated that BP hydrogels loaded with BMSC-derived exosomes had favourable biocompatibility and could promote the proliferation and osteogenic differentiation of MSCs. Experiments conducted in vivo confirmed that this system significantly promoted bone regeneration. Therefore, the results of our study indicated that the nanoplatform based on BP thermosensitive hydrogels could provide a new clinical treatment strategy for controlled release and on-demand drug delivery, while the cell-free system composed of BMSC-derived exosomes had great application potential in bone tissue repair with the synergism of BP.

Black phosphorus thermosensitive hydrogels loaded with bone marrow mesenchymal stem cell-derived exosomes synergistically promote bone tissue defect repair.

Tissue engineering of hair follicles (HFs) has enormous potential for hair loss treatment. However, certain challenges remain, including weakening of the dermal papilla cell (DPC) viability, proliferation, and HF inducibility, as well as the associated inefficient and tedious preparation process required to generate extracellular matrix (ECM)-mimicking substrates for biomolecules or cells. Herein, we utilized gelatin methacryloyl (GelMA) and chitosan hydrogels to prepare scalable, monodispersed, and diameter-controllable interpenetrating network GelMA/chitosan-microcarriers (IGMs) loaded with platelet-rich plasma (PRP) and seeded with DPCs, on a high-throughput microfluidic chip.The ECM-mimicking hydrogels used for IGMs exhibited surface nano-topography and high porosity. Mass production of IGMs with distinct and precise diameters was achieved by adjusting the oil and aqueous phase flow rate ratio. Moreover, IGMs exhibited appropriate swelling and sustained growth factor release to facilitate a relatively long hair growth phase. DPCs seeded on PRP-loaded IGMs exhibited good viability (> 90%), adhesion, spreading, and proliferative properties (1.2-fold greater than control group). Importantly, PRP-loaded IGMs presented a higher hair inducibility of DPCs in vitro compared to the control and IGMs group (p < 0.05). Furthermore, DPC/PRP-laden IGMs were effectively mixed with epidermal cell (EPC)-laden GelMA to form a PRP-loaded DPC/EPC co-cultured hydrogel system (DECHS), which was subcutaneously injected into the hypodermis of nude mice. The PRP-loaded DECHS generated significantly more HFs (~ 35 per site) and novel vessels (~ 12 per site) than the other groups (p < 0.05 for each).Taken together, these results illustrate that, based on high-throughput microfluidics, we obtained scalable and controllable production of ECM-mimicking IGMs and DECHS, which simulate an effective micro- and macro-environment to promote DPC bioactivity and hair regeneration, thus representing a potential new strategy for HF tissue engineering. 

/pdf/scalable-and-high-throughput-production-of-an-injectable-mdz2wag9.pdf

Scalable and high-throughput production of an injectable platelet-rich plasma (PRP)/cell-laden microcarrier/hydrogel composite system for hair follicle tissue engineering

The study aimed to compare the dentoskeletal effects of Vanbeek Activator, Herbst, Twin-Block and Mandibular Advancement with clear aligners in children with skeletal Class II malocclusions.A sample with sixty-three patients (37 males, 26 females) was included and divided into untreated control group (C, n = 12), Vanbeek Activator group (V, n = 14), Herbst group (H, n = 11), Twin-Block group (TB, n = 12) and MA group (MA, n = 14). Cephalometric analysis and Johnston Pitchfork analysis were performed to quantify the skeletal and dentoalveolar components in molar relationship and overjet correction. Compare the differences of cephalometric data and Johnston-analysis data.The treatment changes showed significant differences in SNB, FH-NP, NA-PA, Co-Go, Co-Pog, ANB, lower facial height ratio, U1-PP, U6-PP, L1-MP and U1-L1. All the appliances improved overjet relationships significantly (Vanbeek, Herbst, Twin-Block and MA were 2.77 mm, 5.53 mm, 4.73 mm and 3.66 mm respectively) with significant retraction of maxillary incisors. The lower incisor displacement of group V and MA was negative, while that of group H and TB was positive and there were significant differences. Molar relationships were also improved by 3.45 mm, 6.85 mm, 3.48 mm and 0.92 mm for Vanbeek, Herbst, Twin-Block and MA. Mandible displacement showed a trend of group H > TB > V > MA. The displacement of maxillary molars in group H was greater than that in group C, TB and MA, and that of mandibular ones was greater than that in group C, V and MA, significantly. Herbst, Twin-Block and MA have more significant dentoalveolar effect than Vanbeek, while Vanbeek has more skeletal effect than the others especially in restraining maxillary growth.Four appliances are all effective in mandibular advancement, modification of class II molar relationship and deep overjet, with unavoidable increase in lower facial ratio. Vanbeek Activator has the most skeletal effects. Vanbeek and MA have a good control of mandibular incisors while more compensatory lower incisors proclination in Herbst and Twin-Block. Herbst has greater maxillary molar distalization. MA allows aligning and leveling meanwhile leading the mandible forward. 

/pdf/does-mandibular-advancement-with-clear-aligners-have-the-2e713c4c.pdf

Does mandibular advancement with clear aligners have the same skeletal and dentoalveolar effects as traditional functional appliances?

The repair of tissue defects has attracted considerable attention and remained a substantial challenge. Calcium silicate (CaSiO3, CS) bioceramics have attracted the interest of researchers due to their excellent biodegradability. Recent studies have demonstrated that nanoscale-modified bioactive materials with favorable biodegradability could promote bone tissue regeneration, providing an alternative approach for the repair of bone defects. However, the direct construction of biodegradable nanostructures in situ on CS bioceramics was still difficult.In this study, flower-like nanostructures were flexibly prepared in situ on biodegradable CS bioceramics via hydrothermal treatment. The flower-like nanostructure surfaces exhibited better hydrophilicity and more significantly stimulated cell adhesion, alkaline phosphatase (ALP) activity, and osteogenic differentiation. Furthermore, the CS bioceramics with flower-like nanostructures effectively promoted bone regeneration and were gradually replaced with newly formed bone due to the favorable biodegradability of these CS bioceramics. Importantly, we revealed an osteogenesis-related mechanism by which the FAK/p38 signaling pathway could be involved in the regulation of bone mesenchymal stem cell (BMSC) osteogenesis by the flower-like nanostructure surfaces.Flower-like nanostructure surfaces on CS bioceramics exerted a strong effect on promoting bone repair and regeneration, suggesting their excellent potential as bone implant candidates for improving bone regeneration. 

/pdf/in-situ-construction-of-flower-like-nanostructured-calcium-njyvrvhe.pdf

In situ construction of flower-like nanostructured calcium silicate bioceramics for enhancing bone regeneration mediated via FAK/p38 signaling pathway

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Does mandibular advancement with clear aligners have the same skeletal and dentoalveolar effects as traditional functional appliances?

In situ construction of flower-like nanostructured calcium silicate bioceramics for enhancing bone regeneration mediated via FAK/p38 signaling pathway