A rabbit osteochondral defect (OCD) model for evaluation of tissue engineered implants on their biosafety and efficacy in osteochondral repair.

Osteochondral defect (OCD) is a common but challenging condition in orthopaedics that imposes huge socioeconomic burdens in our aging society. It is imperative to accelerate the R&D of regenerative scaffolds using osteochondral tissue engineering concepts. Yet, all innovative implant-based treatments require animal testing models to verify their feasibility, biosafety, and efficacy before proceeding to human trials. Rabbit models offer a more clinically relevant platform for studying OCD repair than smaller rodents, while being more cost-effective than large animal models. The core-decompression drilling technique to produce full-thickness distal medial femoral condyle defects in rabbits can mimic one of the trauma-relevant OCD models. This model is commonly used to evaluate the implant's biosafety and efficacy of osteochondral dual-lineage regeneration. In this article, we initially indicate the methodology and describe a minimally-invasive surgical protocol in a step-wise manner to generate a standard and reproducible rabbit OCD for scaffold implantation. Besides, we provide a detailed procedure for sample collection, processing, and evaluation by a series of subsequent standardized biochemical, radiological, biomechanical, and histological assessments. In conclusion, the well-established, easy-handling, reproducible, and reliable rabbit OCD model will play a pivotal role in translational research of osteochondral tissue engineering.

Black phosphorus boosts wet-tissue adhesion of composite patches by enhancing water absorption and mechanical properties.

Wet-tissue adhesives have long been attractive materials for realizing complicated biomedical functions. However, the hydration film on wet tissues can generate a boundary, forming hydrogen bonds with the adhesives that weaken adhesive strength. Introducing black phosphorus (BP) is believed to enhance the water absorption capacity of tape-type adhesives and effectively eliminate hydration layers between the tissue and adhesive. This study reports a composite patch integrated with BP nanosheets (CPB) for wet-tissue adhesion. The patch's improved water absorption and mechanical properties ensure its immediate and robust adhesion to wet tissues. Various bioapplications of CPB are demonstrated, such as rapid hemostasis (within ~1-2 seconds), monitoring of physical-activity and prevention of tumour-recurrence, all validated via in vivo studies. Given the good practicability, histocompatibility and biodegradability of CPB, the proposed patches hold significant promise for a wide range of biomedical applications.

Time-Sequential and Multi-Functional 3D Printed MgO2 /PLGA Scaffold Developed as a Novel Biodegradable and Bioactive Bone Substitute for Challenging Postsurgical Osteosarcoma Treatment.

Osteosarcoma (OS) is the most commonly occurring primary bone malignant tumor. The clinical postsurgical OS treatment faces big challenges for the staged therapeutic requirements of early anti-tumor, anti-bacterial, and long-lasting osteogenesis. Herein, multi-functional bioactive scaffolds with time-sequential functions of preventing tumor recurrence, inhibiting bacterial infection, and promoting bone defect repair are designed as a novel strategy. Nanocomposite scaffold magnesium peroxide (MgO2 )/poly (lactide-co-glycolide) is prepared by low-temperature 3D printing for controllable releasing magnesium ions (Mg2+ ) and reactive oxygen species in a time-sequential manner. The scaffold with 20 wt% MgO2 (20MP) is verified with desired mechanical properties, as well as exhibits staged release behavior of bioactive elements with hydrogen peroxide (H2 O2 ) release for the first 3 weeks, and long-lasting Mg2+ release for 12 weeks. The released H2 O2 initiates chemodynamic therapy to induce apoptosis and ferroptosis in tumor cells, along with activating the anticancer immune microenvironment by M1 polarization of macrophages. The released Mg2+ subsequently enhances bone repair by activating the Wnt3a/GSK-3ß/ß-catenin signaling pathway to promote osteogenic differentiation of bone marrow mesenchymal stem cells and create osteopromotive immune microenvironment by M2 polarization of macrophages. In conclusion, the multi-functional 20MP scaffold demonstrates time-sequential therapeutic properties as an innovative strategy for OS-associated bone defect treatment.

Regulation of Osteoimmune Microenvironment and Osteogenesis by 3D-Printed PLAG/black Phosphorus Scaffolds for Bone Regeneration.

The treatment of bone defects remains a significant challenge to be solved clinically. Immunomodulatory properties of orthopedic biomaterials have significance in regulating osteoimmune microenvironment for osteogenesis. A lactic acid-co-glycolic acid (PLGA) scaffold incorporates black phosphorus (BP) fabricated by 3D printing technology to investigate the effect of BP on osteoimmunomodulation and osteogenesis in site. The PLGA/BP scaffold exhibits suitable biocompatibility, biodegradability, and mechanical properties as an excellent microenvironment to support new bone formation. The studies' result also demonstrate that the PLGA/BP scaffolds are able to recruit and stimulate macrophages M2 polarization, inhibit inflammation, and promote human bone marrow mesenchymal stem cells (hBMSCs) proliferation and differentiation, which in turn promotes bone regeneration in the distal femoral defect region of steroid-associated osteonecrosis (SAON) rat model. Moreover, it is screened and demonstrated that PLGA/BP scaffolds can promote osteogenic differentiation by transcriptomic analysis, and PLGA/BP scaffolds promote osteogenic differentiation and mineralization by activating PI3K-AKT signaling pathway in hBMSC cells. In this study, it is shown that the innovative PLGA/BP scaffolds are extremely effective in stimulating bone regeneration by regulating macrophage M2 polarization and a new strategy for the development of biomaterials that can be used to repair bone defects is offered.

Alterations in the microenvironment and the effects produced of TRPV5 in osteoporosis.

The pathogenesis of osteoporosis involves multiple factors, among which alterations in the bone microenvironment play a crucial role in disrupting normal bone metabolic balance. Transient receptor potential vanilloid 5 (TRPV5), a member of the TRPV family, is an essential determinant of the bone microenvironment, acting at multiple levels to influence its properties. TRPV5 exerts a pivotal influence on bone through the regulation of calcium reabsorption and transportation while also responding to steroid hormones and agonists. Although the metabolic consequences of osteoporosis, such as loss of bone calcium, reduced mineralization capacity, and active osteoclasts, have received significant attention, this review focuses on the changes in the osteoporotic microenvironment and the specific effects of TRPV5 at various levels.

Injectable spontaneous hydrogen-releasing hydrogel for long-lasting alleviation of osteoarthritis.

Excessive production of reactive oxygen species (ROS) amplifies pro-inflammatory pathways and exacerbates immune responses, and is a key factor in the progression of osteoarthritis (OA). Therapeutic hydrogen gas (H2) with antioxidative and anti-inflammatory effects, has a potential for OA alleviation, but the targeted delivery and sustained release of H2 are still challenging. Herein, we develop an injectable calcium boride nanosheets (CBN) loaded hydrogel platform (CBN@GelDA hydrogel) as a high-payload and sustainable H2 precursor for OA treatment. The CBN@GelDA hydrogel could maintain constant physiological pH conditions which further promotes more H2 release than the CBN alone and lasts more than one week. The biocompatibility of this hydrogel with macrophages and chondrocytes is effectively enhanced. The experiments show that the CBN@GelDA hydrogel holds the ROS scavenging ability, reducing the expression of related inflammatory cytokines, lessening M1 macrophages but stimulating M2 phenotype, and thereby decreasing chondrocyte apoptosis, which facilitates to breaking of the vicious circle of OA progression. Furthermore, a single-time injection of the CBN@GelDA hydrogel markedly reduces joint destruction in OA rats. From what has been discussed above, this injectable spontaneous H2-releasing hydrogel is promising for OA treatment. STATEMENT OF SIGNIFICANCE: Oxidative stress and inflammation play the key role in the occurrence and development of osteoarthritis (OA). The system of a hydrogel loaded with H2 precursor calcium boride nanosheet (CBN), which is the first to use as an H2 precursor, integrates superior injectable and biocompatible of hydrogel and the selection of antioxidant properties of H2. This system can improve H2 release behavior and achieve a single injection into the articular cavity to alleviate the progression of OA in rats. This study of the combination of a convenient long-acting injectable hydrogel and a safe therapeutic gas is of great value for improving the quality of life of clinical patients.

Biomechanics evaluation of sacroiliac joint pain after lumbosacral fusion: A finite element analysis.

The sacroiliac joint (SIJ) constitutes the predominant pain source following lumbar or lumbosacral fusion. Although studies have investigated the biomechanical patterns of SIJ behaviors after lumbosacral fusion, the relationship between ligament strain and SIJ pain following lumbosacral fusion remains unclear. The present study developed a three-dimensional finite element model including L4, L5, sacrum, ilium, SIJ, and seven mainly ligaments. After successful validation, the model was used to investigate the biomechanics of SIJ and ligaments in simulating lumbosacral fusion process. Our results showed that small motion in a stable SIJ may significantly increases the contact pressure and stress of the SIJ, which increase the maximum contact pressure by 171%, 676%, 199%, and 203% and stress by 130%, 424%, 168%, and 241% for flexion, extension, bending, and axial rotation, respectively. An increase in contact pressure and stress in SIJ possibly causes pain at the SIJ, especially in extension and axial rotation. A comparison between the lumbosacral and intact models exhibited the maximum strain increase in the iliosacral ligament (ISL) and the ileal ligament (IL) under all loading conditions. The present study suggests that after lumbosacral fusion process, the ligament sudden increase or decrease is likely to lead sprain or strain ligament, especially ISL and IL thereby causing SIJ pain. This study may contribute to understand the relationship between SIJ ligaments and SIJ pain.

PDGF-BB prevents destructive repair and promotes reparative osteogenesis of steroid-associated osteonecrosis of the femoral head in rabbits.

Destructive repair characterized by inadequate angiogenesis and osteogenesis is the main pathological progression in steroid-associated osteonecrosis of the femoral head (SONFH). Platelet-derived growth factor-BB (PDGF-BB) is an "angiogenesis and osteogenesis coupling" factor that has been used for the treatment of bone defects in clinic. This study was designed to analyze the ability of PDGF-BB for preventing destructive repair and promoting reparative osteogenesis in SONFH. Steroid-associated osteonecrosis (SAON) was induced and triggered destructive repair of the femoral head by repeated lipopolysaccharide (LPS) and methylprednisolone (MPS) injections in rabbits. At 2, 4, and 6 weeks after induction, recombinant human PDGF-BB, neutralizing PDGF-BB antibody, or saline was intramedullary injected into the proximal femora. At week 6 after SAON induction, the proximal femora were dissected for bone architecture and histological analysis. C3H10T1/2 cells and HUVECs were used for further mechanistic investigation. After PDGF-BB treatment, type H vessels and leptin receptor-positive (LepR+) mesenchymal stem cells (MSCs) increased in the affected femoral head, and more osteoblastic osteogenesis along the bone surfaces but scattered adipocytes in bone marrow tissue than that in the SAON group. PDGF-BB treatment prevented destructive repair progression and led to 50-70 % of osteonecrotic femoral heads undergoing reparative osteogenesis. In particular, we found that PDGF-BB could mediate MSC self-renewal and maintain their osteogenic potency by activating PDGFR/Akt/GSK3ß/CERB signaling in the presence of steroids. Moreover, PDGF-BB also stabled the newly formed vascular tubes by recruiting MSCs for improving intraosseous vascular integration. PDGF-BB may be a candidate for the promotion of reparative osteogenesis in SONFH.

Controlled Release of Bone Morphogenetic Protein-2 Augments the Coupling of Angiogenesis and Osteogenesis for Accelerating Mandibular Defect Repair.

Reconstruction of a mandibular defect is challenging, with high expectations for both functional and esthetic results. Bone morphogenetic protein-2 (BMP-2) is an essential growth factor in osteogenesis, but the efficacy of the BMP-2-based strategy on the bone regeneration of mandibular defects has not been well-investigated. In addition, the underlying mechanisms of BMP-2 that drives the bone formation in mandibular defects remain to be clarified. Here, we utilized BMP-2-loaded hydrogel to augment bone formation in a critical-size mandibular defect model in rats. We found that implantation of BMP-2-loaded hydrogel significantly promoted intramembranous ossification within the defect. The region with new bone triggered by BMP-2 harbored abundant CD31+ endomucin+ type H vessels and associated osterix (Osx)+ osteoprogenitor cells. Intriguingly, the new bone comprised large numbers of skeletal stem cells (SSCs) (CD51+ CD200+) and their multi-potent descendants (CD51+ CD105+), which were mainly distributed adjacent to the invaded blood vessels, after implantation of the BMP-2-loaded hydrogel. Meanwhile, BMP-2 further elevated the fraction of CD51+ CD105+ SSC descendants. Overall, the evidence indicates that BMP-2 may recapitulate a close interaction between functional vessels and SSCs. We conclude that BMP-2 augmented coupling of angiogenesis and osteogenesis in a novel and indispensable way to improve bone regeneration in mandibular defects, and warrants clinical investigation and application.

Phenoxyl mediators improve enzymatic degradation of organic pollutants: Effect and mechanism.

A mediation strategy can effectively overcome the low reaction activity of enzymes with nonspecific substrates. In this study, we demonstrated how phenol compounds can mitigate the substrate limitation of HRP in catalytic degradation of various organic pollutants. In a classical HRP/H2O2 system, phenol and natural phenolic compounds (4-HBA & pHBA), exhibited up to over 100-fold enhancement in eliminating organic dyes and persistent antibiotics while the loading is only 2-5 wt%. A combination of molecular modelling, docking and frontier orbital energy analysis was employed to elucidate the catalytic performance and mechanism. We revealed that (1) generating phenoxyl radicals required the proximity of mediators to the HRP active centre, and (2) the subsequent efficient radical transfer to pollutants was determined by the large energy gap between the SOMO energy of phenoxyl radicals and the HOMO energy of phenols. When considering phenols as pollutants, we showed a synergistic effect on catalytic degradation of phenols, dyes, and tetracycline with a removal efficiency of 71-92 %. Overall, this work not only demonstrates that phenoxyl mediators can overcome the lower efficiency and substrate-specificity limitations of the HRP/H2O2 system but also revealed their structure-mediation relationship, implying great potential in the biodegradation of diverse pollutants and their mixtures.

Brominated cyclometalated iridium(III) complexes for mitochondrial immobilization as potential anticancer agents.

Mitochondria-targeted iridium complexes for anticancer studies have received increasing attention in recent years. Herein, three cyclometalated iridium(III) complexes Ir1-Ir3 [Ir(N^C)2(N^N)](PF6) (N^N = 2,2'-bipyridine (bpy)) or 2-(5-bromopyridin-2-yl)benzo[d]thiazole (bpybt); [N^C = 2-phenylpyridine (ppy) or 2-phenylquinoline (pq) or 2-(4-bromophenyl)benzo[d]thiazole (bpbt)] had been explored as potential mitochondria-targeted anticancer agents. All of the complexes mainly localized in the mitochondria and could be fixed on the mitochondria through a nucleophilic reaction with reactive mitochondrial proteins. Further studies revealed that these complexes showed high anticancer activity, induced mitochondrial depolarization, elevated intracellular reactive oxygen species (ROS) levels, restrained thioredoxin reductase (TrxR) activity, and inhibited the formation of tumor cell colonies and angiogenesis. Further mechanistic studies showed that complex Ir2 could markedly stimulate the activation of caspase-3, regulate the expression of Bax and KI67, and trigger apoptosis.

Preparation and characterization of photocurable composite extracellular matrix-methacrylated hyaluronic acid bioink.

Producing a bioink that fulfills the physicochemical requirements of printing and provides a desirable environment for encapsulated cells is a major challenge in three-dimensional (3D) bioprinting. Thus, we have developed a biocompatible bioink (ECM@MeHA bioink) with suitable mechanical support and visible light printable properties. In this bioink system, the thermosensitive extracellular matrix (ECM) was prepared and can be crosslinked at 37 °C. And the prepared methacrylated hyaluronic acid (MeHA) can be crosslinked under visible light using the biosafe initiators (Eosin Y, TEOA, and NVP). Thus, the ECM@MeHA bioink consisted of a mix solution of ECM and MeHA containing visible light initiators can cure at 515 nm visible light for 30 s and then further crosslinked at 37 °C to form a double network hydrogel. Then, the mechanical properties and biocompatibility of ECM@MeHA hydrogel, and the printability and the cell viability of the ECM@MeHA bioink were systemically evaluated. The results showed that the mechanical property of the MeHA hydrogel is significantly improved following the addition of 10 mg mL-1 of ECM (10ECM@MeHA). The compressive strength and modulus of 10ECM@MeHA hydrogel were 102.38 ± 5.27 kPa and 782 ± 20.36 kPa, which were 2.7 times and 3.1 times higher than those of MeHA, respectively. After encapsulating MC3T3-E1 cells in the 10ECM@MeHA hydrogel for 7 days, the culture showed excellent biocompatibility. The 10ECM@MeHA bioink and cell-laden 10ECM@MeHA bioink were printed, and the cells were successfully encapsulated by the extrusion-based bioprinting and digital light processing (DLP) -based bioprinting. The cell-laden 10ECM@MeHA scaffold showed 94.27 ± 3.00% cell viability after 7 days of the 3D culture. In conclusion, 10ECM@MeHA bioink may provide a new strategy for constructing disease models or drug screening models in vitro and is expected to be widely used in the field of tissue engineering scaffolds.

Long-term mechanical loading is required for the formation of 3D bioprinted functional osteocyte bone organoids.

Mechanical loading has been shown to influence various osteogenic responses of bone-derived cells and bone formationin vivo. However, the influence of mechanical stimulation on the formation of bone organoidin vitrois not clearly understood. Here, three-dimensional (3D) bioprinted human mesenchymal stem cells-laden graphene oxide composite scaffolds were cultured in a novel cyclic-loading bioreactors for up to 56 d. Our results showed that mechanical loading from day 1 (ML01) significantly increased organoid mineral density, organoid stiffness, and osteoblast differentiation compared with non-loading and mechanical loading from day 21. Importantly, ML01 stimulated collagen I maturation, osteocyte differentiation, lacunar-canalicular network formation and YAP expression on day 56. These finding are the first to reveal that long-term mechanical loading is required for the formation of 3D bioprinted functional osteocyte bone organoids. Such 3D bone organoids may serve as a human-specific alternative to animal testing for the study of bone pathophysiology and drug screening.

3D-printed NIR-responsive shape memory polyurethane/magnesium scaffolds with tight-contact for robust bone regeneration.

Patients with bone defects suffer from a high rate of disability and deformity. Poor contact of grafts with defective bones and insufficient osteogenic activities lead to increased loose risks and unsatisfied repair efficacy. Although self-expanding scaffolds were developed to enhance bone integration, the limitations on the high transition temperature and the unsatisfied bioactivity hindered greatly their clinical application. Herein, we report a near-infrared-responsive and tight-contacting scaffold that comprises of shape memory polyurethane (SMPU) as the thermal-responsive matrix and magnesium (Mg) as the photothermal and bioactive component, which fabricated by the low temperature rapid prototyping (LT-RP) 3D printing technology. As designed, due to synergistic effects of the components and the fabrication approach, the composite scaffold possesses a homogeneously porous structure, significantly improved mechanical properties and stable photothermal effects. The programmed scaffold can be heated to recover under near infrared irradiation in 60s. With 4 wt% Mg, the scaffold has the balanced shape fixity ratio of 93.6% and shape recovery ratio of 95.4%. The compressed composite scaffold could lift a 100 g weight under NIR light, which was more than 1700 times of its own weight. The results of the push-out tests and the finite element analysis (FEA) confirmed the tight-contacting ability of the SMPU/4 wt%Mg scaffold, which had a signficant enhancement compared to the scaffold without shape memory effects. Furthermore, The osteopromotive function of the scaffold has been demonstrated through a series of in vitro and in vivo studies. We envision this scaffold can be a clinically effective strategy for robust bone regeneration.

Recent Advances of Microneedles and Their Application in Disease Treatment.

For decades, scientists have been doing a lot of research and exploration to find effective long-term analgesic and/or disease-modifying treatments. Microneedles (MNs) are a simple, effective, and painless transdermal drug delivery technology that has emerged in recent years, and exhibits great promise for realizing intelligent drug delivery. With the development of materials science and fabrication technology, the MN transdermal drug delivery technology has been applied and popularized in more and more fields, including chronic illnesses such as arthritis or diabetes, cancer, dermatocosmetology, family planning, and epidemic disease prevention, and has made fruitful achievements. This paper mainly reviews the latest research status of MNs and their fabrication methodology, and summarizes the application of MNs in the treatment of various diseases, as well as the potential to use nanotechnology to develop more intelligent MNs-based drug delivery systems.

Kindlin-2 inhibits Nlrp3 inflammasome activation in nucleus pulposus to maintain homeostasis of the intervertebral disc.

Intervertebral disc (IVD) degeneration (IVDD) is the main cause of low back pain with major social and economic burdens; however, its underlying molecular mechanisms remain poorly defined. Here we show that the focal adhesion protein Kindlin-2 is highly expressed in the nucleus pulposus (NP), but not in the anulus fibrosus and the cartilaginous endplates, in the IVD tissues. Expression of Kindlin-2 is drastically decreased in NP cells in aged mice and severe IVDD patients. Inducible deletion of Kindlin-2 in NP cells in adult mice causes spontaneous and striking IVDD-like phenotypes in lumbar IVDs and largely accelerates progression of coccygeal IVDD in the presence of abnormal mechanical stress. Kindlin-2 loss activates Nlrp3 inflammasome and stimulates expression of IL-1ß in NP cells, which in turn downregulates Kindlin-2. This vicious cycle promotes extracellular matrix (ECM) catabolism and NP cell apoptosis. Furthermore, abnormal mechanical stress reduces expression of Kindlin-2, which exacerbates Nlrp3 inflammasome activation, cell apoptosis, and ECM catabolism in NP cells caused by Kindlin-2 deficiency. In vivo blocking Nlrp3 inflammasome activation prevents IVDD progression induced by Kindlin-2 loss and abnormal mechanical stress. Of translational significance, adeno-associated virus-mediated overexpression of Kindlin-2 inhibits ECM catabolism and cell apoptosis in primary human NP cells in vitro and alleviates coccygeal IVDD progression caused by mechanical stress in rat. Collectively, we establish critical roles of Kindlin-2 in inhibiting Nlrp3 inflammasome activation and maintaining integrity of the IVD homeostasis and define a novel target for the prevention and treatment of IVDD.

Engineering Supramolecular Nanomedicine for Targeted Near Infrared-triggered Mitochondrial Dysfunction to Potentiate Cisplatin for Efficient Chemophototherapy.

Combinatorial cancer therapies based on nanomedicine have emerged as a promising strategy to achieve potentiated treatment efficiency. Herein, cisplatin (CDDP) prodrug (Pt-CD) and a mitochondria-targeted near-infrared (NIR) photosensitizer IR780 were combined to construct a multifunctional nanomedicine IR780@Pt NPs through a supramolecular self-assembly strategy. Targeted mitochondrial dysfunction of cancer cells was sufficiently induced under NIR laser irradiation through both photothermal and photodynamic effects, inhibiting the overactive mitochondrial energy pathways of cancer cells. The mitochondrial dysfunction significantly attenuated the crosstalk between mitochondria and nucleus via the cellular ATP energy chain, leading to obvious down-regulation of the key proteins of the nucleotide excision repair (NER) pathway. Thereby, the chemotherapeutic effect of CDDP could be significantly potentiated because of reduced DNA lesion repair capacity by ERCC1-XPF nuclease system. Moreover, IR780@Pt NPs exhibited excellent NIR fluorescence and photoacoustic (PA) imaging capacity for in vivo imaging-guided NIR laser treatment. Ultimately, the IR780@Pt NPs mediated combinatorial chemophototherapy achieved potentiated anticancer efficacy against cancer cells in vitro and tumor inhibition performance in vivo. Overall, this study highlighted the significance of nanomedicine mediated targeted induction of mitochondrial dysfunction to potentiate chemotherapy for efficient combinatorial cancer therapy.

LL-37-Coupled Porous Composite Scaffold for the Treatment of Infected Segmental Bone Defect.

Increased multiantibiotic-resistant bacteria means that infected bone defects remain a significant challenge to clinics. Great interest has emerged in the use of non-antibiotic antimicrobials to reduce the rate of multiantibiotic-resistant bacterial infection and facilitate bone regeneration. The cationic antimicrobial peptide LL-37 is the sole human cathelicidin and has shown nonspecific activity against a broad spectrum of microorganisms. In this study, we fabricated the poly(lactic-co-glycolic acid)/ß-calcium phosphate/peptide LL-37 (PLGA/TCP/LL-37, PTL) scaffold with low-temperature 3D-printing technology for the treatment of infected segmental bone defects. The prepared scaffolds were divided into three groups: a high LL-37 concentration group (PTHL), low LL-37 concentration group (PTLL) and blank control group (PT). The cytocompatibility and antimicrobial activity of the engineered scaffolds were tested in vitro, and their osteogenesis properties were assessed in vivo in a rat infected bone defect model. We found the fabricated PTL scaffold had a well-designed porous structure that could support a steady and prolonged LL-37 release. Furthermore, the PTHL group showed strong antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) without any inhibition of the proliferation or alkaline phosphatase activity of rat bone marrow mesenchymal stem cells (BMSCs) in vitro. In addition, the infected femoral defects implanted with PTHL group displayed new bone formation in four weeks without any evidence of residual bacteria, which showed similar antibacterial outcomes to the vancomycin and cancellous bone mixture group. In conclusion, the PTHL composite scaffold is a promising non-antibiotic antimicrobial graft with good biodegradability, biocompatibility, and osteogenic capability for infected bone defects.

Advances and Prospects in Biomaterials for Intervertebral Disk Regeneration.

Low-back and neck-shoulder pains caused by intervertebral disk degeneration are highly prevalent among middle-aged and elderly people globally. The main therapy method for intervertebral disk degeneration is surgical intervention, including interbody fusion, disk replacement, and diskectomy. However, the stress changes caused by traditional fusion surgery are prone to degeneration of adjacent segments, while non-fusion surgery has problems, such as ossification of artificial intervertebral disks. To overcome these drawbacks, biomaterials that could endogenously regenerate the intervertebral disk and restore the biomechanical function of the intervertebral disk is imperative. Intervertebral disk is a fibrocartilaginous tissue, primarily comprising nucleus pulposus and annulus fibrosus. Nucleus pulposus (NP) contains high water and proteoglycan, and its main function is absorbing compressive forces and dispersing loads from physical activities to other body parts. Annulus fibrosus (AF) is a multilamellar structure that encloses the NP, comprises water and collagen, and supports compressive and shear stress during complex motion. Therefore, different biomaterials and tissue engineering strategies are required for the functional recovery of NP and AF based on their structures and function. Recently, great progress has been achieved on biomaterials for NP and AF made of functional polymers, such as chitosan, collagen, polylactic acid, and polycaprolactone. However, scaffolds regenerating intervertebral disk remain unexplored. Hence, several tissue engineering strategies based on cell transplantation and growth factors have been extensively researched. In this review, we summarized the functional polymers and tissue engineering strategies of NP and AF to endogenously regenerate degenerative intervertebral disk. The perspective and challenges of tissue engineering strategies using functional polymers, cell transplantation, and growth factor for generating degenerative intervertebral disks were also discussed.