BMJ Open Sport and Exercise Medicine

ABSTRACTInjectable carbonated hydroxyapatite (ICHA) cement was developed by adding 2% Hydroxypropyl methylcellulose (HPMC) to carbonated hydroxyapatite (CHA) cement, improving its rheological properties and injectability for minimally invasive orthopedic use. The cement's physical and chemical properties, including curing time, strength, porosity, and consistency, were tested in vitro. Scanning electron microscopy, X‐ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to analyze the cured cement. Bone marrow stromal cells were cultured with ICHA cement extracts and specimens to test cell growth (MTT assay) and cytotoxicity. In vivo, the cement was implanted into rabbit muscles to assess inflammation and capsule formation, along with other biocompatibility tests, including hemolysis and pyrogen testing. ICHA cement sets without heat generation, with a 9‐min initial setting time and a 15‐min final setting time, similar to CHA cement. The strength reaches 20 MPa after 1 day and peaks at 35 MPa after 7 days. Its porosity is slightly higher than CHA cement, and it resists dilution well, preventing disintegration in water. The consistency of ICHA cement is lower than CHA cement at different time points (p < 0.001), showing a logarithmic change pattern. With adjustable setting time, good resistance to dilution, and compressive strength similar to cancellous bone, ICHA cement is well suited for clinical use. Its composition closely resembles natural bone, offering strong fixation and stability for tibial plateau healing, which supports early movement and reduces the risk of joint stiffness and post‐traumatic arthritis.

ABSTRACTTo examine natural bone's bioelectrical traits, notably its piezoelectricity, and to look into how these characteristics influence bone growth and repair. In the context of exploring the potential of piezoelectric biomaterials, such as biopolymers and bio‐ceramics, towards orthopedic and bone regeneration applications, the research seeks to evaluate the significance of piezoelectricity‐driven osteogenesis. The paper reviews recent research on bone's electrical and dielectric properties, surface polarization/electrical stimulation effects interacting with cell activity and the effectiveness of piezoelectric biomaterials to support tissues' regenerative process. The study includes a number of materials, such as collagen, polyvinylidene fluoride (PVDF) and barium titanate. The applications of piezoelectric bio‐ceramics, piezoelectric organic polymers, and piezoelectric natural polymers are particularly highlighted. Piezoelectric biomaterials are being shown in recent studies to enhance cellular metabolism in vitro as well as promote the regeneration of tissues in vivo, especially when paired with electric field stimulation or interface polarization. Piezoelectric bio‐ceramics like magnesium silicate and barium titanate, as well as biopolymers like collagen and PVDF, have shown possibilities for orthopedic applications. However, there are several challenges regarding the manufacturing of bio‐ceramics of specific compositions having the desired properties. This review highlighted the potential of piezoelectric biomaterials in orthopedic applications with special emphasis on biopolymers and bioceramics. Therefore, these types of materials have huge potential for bone regeneration because they can mimic the piezoelectric properties of bone and allow better advances in tissue engineering or regenerative medicine. To date, little is known about their mechanism of action, and modifications are needed to improve efficacy for clinical uptake.

ABSTRACTReconstruction of critical‐size bone defects (CSDs) with complex defect morphologies remains clinically challenging. The desire to avoid autograft harvesting has prompted an increasing quest for adequate synthetic bone grafting materials. The clinical success rates, which have been achieved with bioactive β‐tricalcium phosphate granules (TCP‐G) demonstrate that these materials have become an excellent alternative graft choice. In order to improve surgical handling properties, TCP‐G have been combined with natural polymers for creating paste‐ and foam‐like materials, which can easily be molded into any desired shape when grafting a given bony defect or deploying them with a syringe. This study assessed the effect of a TCP paste (TCP‐P) and a TCP‐foam (TCP‐F) bone grafting material as compared to TCP‐G on bone formation and osteogenic marker expression after 1, 3, 6, 12, and 18 months of implantation in CSD in the sheep scapula and tested the hypothesis that the addition of natural polymers would not diminish the osteogenic properties of TCP‐P and TCP‐F. The bone and bone graft material area fractions were determined histomorphometrically in order to quantify bone formation and bone graft material resorption. Immunohistochemical analysis of collagen type I, osteocalcin, and bone sialoprotein expression in the various cell and matrix components of the bone tissue was performed on resin‐embedded sections for characterizing the osteogenic and bioactive properties of the test materials. By 6 months, all three TCP materials facilitated excellent defect regeneration with further bone remodeling at 12 and 18 months. TCP‐F and TCP‐P induced greater osteocalcin expression and exhibited more advanced graft material resorption at 1 and 6 months, respectively. At 18 months, all three grafting materials were almost fully resorbed with the original bony architecture being restored. Taken together, the hyaluronic acid and methylcellulose components in TCP‐P and porcine collagen components in TCP‐F did not diminish the osteogenic capacity of TCP‐P and TCP‐F, which exhibited an even slightly higher resorbability and enhancement effect on OC expression by osteoblasts.

ABSTRACTSkin tissue defects caused by various acute and chronic etiologies frequently occur in clinical medicine. Traditional surgical repair methods have certain limitations, while dermal substitutes combined with skin grafting have become an alternative to conventional surgery. Biological coatings, by loading bioactive substances such as polysaccharides and proteins, or by using bioactive substances as carriers, can promote cell adhesion, proliferation, and differentiation. This optimizes the mechanical properties and biocompatibility of the substitutes, enhances their antibacterial properties, and improves their feasibility for clinical application. This paper explores various common biological coating materials and the construction methods used in the field of dermal substitutes. It highlights the importance and necessity of biological coatings in the development of multifunctional designs for dermal substitutes. By summarizing the current research, this paper aims to offer new insights and references for the multifunctional design and clinical application of dermal substitutes.

ABSTRACTThe challenge of healing burn wounds is significant importance in global healthcare systems, with a high demand for advanced wound dressings to aid in the treatment of such injuries. Promising options include bioactive electrospun scaffolds made from polymers with antimicrobial properties, which can prevent infections and promote faster healing. This study involved the creation of a nanofibrous scaffold using the electrospinning technique, which consisted of polyvinyl alcohol (PVA), alginate (Alg), and Dragon's blood (DB). The scaffold was then analyzed for both its morphology and chemical composition. Results indicated that the DB was present in the nanofibrous scaffold, which had a uniform and unbranched appearance with fibers measuring approximately 300–400 nm in diameter. Additionally, mechanical property testing revealed promising results that fall within the range of human skin. The scaffold's wound healing potential was evaluated through various measurements, including water contact angle, drug release, water vapor permeability, blood compatibility, blood clotting index, and antibacterial activity. Results from an in vivo study on burn wounds showed that scaffolds containing 20% DB exhibited excellent wound healing ability with 80.3% wound closure after 21 days. This was attributed to the highest collagen synthesis, re‐epithelization and remodeling of the burned skin. Therefore, PVA/Alg/DB nanofibrous scaffolds hold promise as a wound dressing to treat burn injuries.

ABSTRACTBone defect repair methods have significant drawbacks and limitations. The discovery and development of bioactive glasses (BGs) have greatly advanced the treatment of bone diseases. BGs can uniquely bond to living tissues, including bone, due to the formation of a hydroxyapatite (HAp) layer on their surface. These glasses synthesized using various catalysts and structure‐directing agents to enhance their biological activities. However, most catalysts generate toxicity, alter pH levels, and work at high concentrations. Similarly, many surfactants have limited surface areas, poor capacity to create well‐defined mesoporous structures, and potential toxicity, reducing the bioactivity, biocompatibility, and biodegradability of the BGs. To address these issues, this study evaluates a bioactive glass synthesized via the sol–gel process, using low concentration CTAB as a structure‐directing agent and citric acid as a catalyst. The phase composition, surface morphology, specific surface area, inner structure, crystal structure, elemental composition, and functional groups of the samples were characterized using X‐ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET), transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy‐dispersive x‐ray spectroscopy (EDS), and Fourier‐transform infrared microscopy (FTIR) techniques, respectively. The in vitro bioactivity was tested by soaking samples in simulated body fluid and analyzing the HAp layer formation using XRD, SEM, and FTIR. In addition, the in vitro biocompatibility, and an in vitro biodegradability were measured. 0.3 M of CTAB (BG3) exhibited a larger specific surface area with spherical‐shaped particles and pore volume with a mesoporous structure results better in bioactivity and biodegradability. Furthermore, all samples exhibited cell viability above 70%, indicating that the prepared materials are biocompatible. The findings highlight the potential of CTAB‐modified BGs for biomedical applications, especially in bone repair and regeneration.

ABSTRACTAlginate dressings are widely used in wound treatment for their healing and hemostatic properties and their capacity to drain exudate. However, a clear understanding of the heterogeneity within this class of dressings is lacking. Numerous sources of variability exist between alginate dressings: their composition (% of calcium alginate relative to other components), the ratio of D‐Mannuronic and L‐Guluronic acids in the alginate fraction, their purity (presence of toxic contaminants), and the shape of their fibers (surface and thickness). These parameters affect the performance and safety of alginate dressings, which may thus not be interchangeable in clinical practice. Therefore, clinicians must be aware of these differences to ensure optimal treatment and avoid complications or suboptimal healing. The objective of this study was to compare six alginate dressings to conclude or not on their equivalence. The results obtained demonstrate considerable variability between alginate dressings in the assessed characteristics: composition, Ca2+ release, level of cytotoxicity, fiber shape, draining capacity, and their resistance to traction. Algostéril, the only pure calcium alginate rich in G, releases a specific dose of Ca2+ and is the only non‐cytotoxic dressing. With its multilobed fibers that are statistically the thickest, it provides the best draining capacity and greatest resistance to traction. These results demonstrate that alginate dressings are not equivalent. Each dressing is distinct, and consequently the clinical performance of one cannot be transposed to the others. Therefore, each alginate dressing should demonstrate its own efficacy, in a given indication, through a clinical trial.

ABSTRACTIn recognizing the critical role of vitamin D in bone metabolism and osseointegration, research aims to identify whether preoperative vitamin D deficiency serves as a risk factor for early implant failure. By analyzing patient outcomes and their serum vitamin D levels, studies seek to establish evidence‐based recommendations for vitamin D assessment and management in the preoperative period, with the ultimate goal of enhancing implant success rates and patient outcomes in dental implantology. Given these insights, it is important for clinicians to incorporate the preoperative evaluation of vitamin D serum levels into their standard protocol for patients undergoing dental implant procedures. The objective of this study is to review and investigate the correlation between early dental implant failure (EDIF) and reduced serum levels of vitamin D, and to evaluate the potential benefits of preoperative screening and supplementation of vitamin D in patients undergoing dental implant surgery. A literature review was performed using a selected database—PubMed, Google Scholar, Cochrane, and SCOPUS—to assess the effect of vitamin D3 level on EDIF and biological factors (i.e., peri‐implant bone level). Studies were limited to peer‐reviewed, indexed journals. Subsequently, a hypothesis was proposed that vitamin D3 supplementation would mitigate the negative effect of vitamin D3 deficiency. The potential benefit of vitamin D3 supplementation—systemic and topical—was assessed in terms of bone‐to‐implant contact (BIC) and peri‐implant bone level. The deleterious effects of low vitamin D serum levels on osseointegration of dental implants and immune system modulation are increasingly accepted. Evidence has displayed that deficiency of this vitamin can result in impaired peri‐implant bone formation. Vitamin D deficiency resulted in nearly a fourfold increase in overall EDIF incidence. Presurgical supplementation of vitamin D3 demonstrated increased levels of implant osseointegration, increased bone–implant contact, enhanced bone level maintenance, and decreased EDIF even in at‐risk demographics (i.e., diabetic subjects). The findings of this study reinforce the role of vitamin D in dental implant osseointegration. Our study, particularly, emphasizes the necessity of vitamin D supplementation for individuals with sub‐physiologic vitamin D serum levels (≤ 30 ng/mL) and those within specific risk categories: smokers, diabetics, obese individuals, and those with compromised immune systems. Adopting a proactive management plan, including screening and supplementation in these patients, may substantially enhance the clinical outcomes in dental implant surgery.

ABSTRACTAs a commonly used material in prosthodontics, zirconia has garnered widespread attention. Addressing the shortcomings of existing zirconia materials, this study aims to investigate the mechanical properties of microporous surface zirconia ceramics and their impact on the biological behavior of human gingival cells. Microporous surface zirconia was developed using a novel ceramic plasticity process, sintered at 1460°C for densification. The surface morphology and composition were determined through scanning electron microscopy and energy dispersive spectrometer. Surface roughness was measured using atomic force microscopy, hydrophilicity angle was determined using a contact angle measurement instrument, and X‐ray diffractometer assessed the crystalline phase content before and after aging. Material flexural strength was determined using a universal testing machine. The influence of microporous surface zirconia on the adhesion and proliferation of human gingival fibroblasts (HGFs) was investigated through CCK‐8 and immunofluorescence staining for Integrin β1 and F‐actin. The pore structure of microporous surface zirconia (MZ) group is uniform, with a flexural strength of 1375.86 ± 76.97 MPa, significantly higher than the control (Cont) group (p < 0.05). The percentage of HGFs adhesion to the MZ group was markedly higher than the Cont group (p < 0.05). Fluorescence of Integrin β1 and F‐actin in the MZ group was significantly higher than in the Cont group. In conclusion, Microporous surface zirconia promotes the attachment and proliferation of human gingival fibroblasts, facilitating early closure of soft tissues.

ABSTRACTOptical fiber technology plays a critical role in modern neuroscience towards understanding the complex neuronal dynamics within the nervous system. In this study, we manufactured and characterized amorphous thermally drawn poly D, L‐lactic acid (PDLLA) biodegradable optical fibers in different diameters. These optical fibers were then implanted into the lateral posterior region of the mouse brain for four months, allowing us to assess their degradation characteristics. The gradual dissolution of the implanted PDLLA optical fibers in the brain was confirmed by optical, photoacoustic, and scanning electron microscopy (SEM), light propagation characteristics, and molecular weight measurements. The results indicate that the degradation rate of the biodegradable optical fiber was mainly pronounced during the first week. After four months, degradation led to the formation of micropores on the surface of the implanted fiber within the gray matter region of the brain. We believe that the PDLLA biodegradable optical fiber developed in this study constitutes a promising candidate for further functionalization and development of next‐generation biocompatible, soft, and biodegradable bi‐directional neural interfaces.

ABSTRACTDespite advances in the design and protocols for maintaining the skin/device interface around percutaneous devices (PDs), no current strategy ensures the permanent attachment of peri‐implant epithelial tissue to the device surface. Based on preliminary data, we hypothesized that PDs coated with keratin nanomaterials, resembling the fingernail‐nailbed interface, could provide a biochemically mediated surface that enhances epidermal cell adhesion and differentiation. To test this hypothesis, 15 Yucatan miniature pigs were each implanted with six percutaneous titanium devices, comprising three porous and three smooth devices, both with and without keratin coatings (Kerateine [iKNT] and Keratose [gKOS]). The pigs were sacrificed at 4, 8, and 16 weeks post‐implantation. The devices and surrounding tissues were harvested and analyzed using histological and RNA sequencing techniques. Compared to smooth peri‐implant tissue, porous peri‐implant tissue showed a significant decrease in epithelial downgrowth, fibrous capsule thickness, and infection rates, alongside a significant upregulation of multiple immune marker genes, including IL12B. At the 16‐week period, gKOS‐coated surfaces demonstrated a more favorable wound healing response than iKTN‐coated devices, with a reduction in granulation tissue area and a significant upregulation of several keratin genes related to differentiation. Among the combinations of surface types and coatings studied, the porous gKOS‐coated device produced the most favorable wound healing response.

ABSTRACTAdditively manufactured polyolefins find broad applications in medical engineering, enabling the manufacturing of patient‐specific geometries. For investigating the influence of processing conditions of laser sintered locally macroporous polypropylene substrates, the response of myoblasts, chondrocytes, and fibroblasts has been characterized in this study. An influence of the applied manufacturing parameters on the attachment and viability of the investigated cells is observed, showing the effect of the superficial pore topology on the attachment and the spreading of cells. The viability and attachment of fibroblasts and chondrocytes could be improved by reducing the thermal exposure during the processing step of the dense base part, associated with increased superficial porosity and the corresponding increase of the surface area. The applied additive manufacturing process of macroporous structures influences emerging cell morphologies, leading to an extended morphological expression of chondrocytes and the overgrowth of small pores by fibroblasts. This indicates an improvement in superficial cell adhesion due to larger pores. These findings indicate the significance of the processing conditions in laser sintering of polypropylene on the cell response through the optimization of processing parameters and the attachment of an open‐cell pore structure.

ABSTRACTThe ongoing rise in the incidences of breast cancer cases has concerned medical and scientific personnel around the world. Adequate treatment of cancer predominantly relies on the pertinent diagnosis of the type of cancer as well as other molecular and cellular details at the initial stage only. Surprisingly, up till now, there is no single, self‐reliant imaging modality that helps to systematically find out the anatomical and functional events taking place inside the body. This resulted in the advent of the multimodal imaging concept, which encompasses the integration of complementary imaging modalities by designing multimodal imaging probes. Gold nanorods (GNRs) are extremely popular and effective nanoparticles for multimodal bioimaging due to their unique properties. Researchers have designed varieties of stable and biocompatible GNR‐based probes for targeted and nontargeted multimodal imaging of breast cancer. However, there is a lack of investigations on the in vivo fate and the toxicity of GNRs. Thus, their preclinical to clinical translation can be attained by comprehensively determining the in vivo fate and toxicity of GNRs. The review provides details about the GNRs‐based nanoprobes fabricated so far for breast cancer imaging, which, by consequent studies, can be taken up to clinical usage.

ABSTRACTMg alloys have recently been investigated and optimized for the development of biodegradable implants for orthopedic, dental, vascular, and other applications. However, their rapid degradation in a physiological environment remains the main obstacle to their development. In this work, the effects of nitrogen and hydrogen plasma treatments on the surface properties and corrosion behavior of an Mg‐2Y‐1Zn‐1Mn (WZM211) alloy were investigated. Plasma treatment effectively modified the surface of a WZM211 alloy by removing the original oxide layer, followed by the formation of a new surface layer with controlled composition, thickness, and wettability. The water contact angle decreased from 100° to 17° after nitrogen plasma and to 45° after hydrogen plasma treatment. The nitrogen plasma treatment, shortly N‐Plasma, resulted in the lowest corrosion rate (CRN = 0.038 ± 0.010 mm/y) if compared with the hydrogen plasma treatment, shortly H‐Plasma (CRH = 0.044 ± 0.003 mm/y) and untreated samples (0.233 ± 0.097 mm/y). The results demonstrate the potential of nitrogen and hydrogen plasma treatment for the development of resorbable Mg‐based implants.

ABSTRACTTraumatic spinal cord injury (SCI) presents a significant medical challenge due to its intricate nature and treatment complexities. SCI can cause physical impairments by affecting neural and motor functions as well as initiating a series of pathophysiological events exacerbating the initial trauma. Leakage from ruptured neurons and vessels disrupt ionic balance and induces excitotoxicity, leading to progressive cellular degeneration. Introducing mitochondria to the SCI lesion has shown potential in attenuating secondary injury. Mitochondria transplantation improves cellular bioenergetics and reduces concentration of reactive oxygen species achieving homeostasis and neuroprotection. Nonetheless, keeping mitochondria viable outside cell environment for a time longer than a few minutes proves to be challenging. Additionally, localized delivery to the injury site has also been limited by other factors including flow rate of cerebrospinal fluid that washes away mobilized organelle from the compromised tissue site. Previously we showed that using hyaluronic acid‐methylcellulose semi‐gels (HAMC) as a biocompatible, erodible thermogelling delivery vehicle helped to overcome some of these challenges. HAMC allows for controlled release at and around the injury site, utilizing the reverse thermogelling property of MC. Sustained release of mitochondria at slower rate can increase their uptake in spinal tissue. To better optimize the semi‐gel delivery of mitochondria requires a more complete understanding of the physicochemical properties of the HAMC semi‐gels. We have used ultraviolet–visible spectroscopy to measure optical density of HAMC semi‐gels for different HA to MC ratios and examine the temperature dependent gelation properties above their low critical solution temperature (LCST). The viscosity and degree of crystallinity of the resulting HAMC semi‐gels were also assessed. Semi‐gel erosion and mitochondrial release over time were studied using a fluorescence microplate reader. Lastly, seahorse assay was used to study released mitochondria respiration and viability after incubation in HAMC semi‐gel.