Bovine xenograft materials, followed by synthetic biomaterials, which unfortunately still lack documented predictability and clinical performance, dominate the market for the cranio‐maxillofacial area. In Europe, new stringent regulations are expected to further limit the allograft market in the future. Aim Within this narrative review, we discuss possible future biomaterials for bone replacement. Scientific Rationale for Study Although the bone graft (BG) literature is overflooded, only a handful of new BG substitutes are clinically available. Laboratory studies tend to focus on advanced production methods and novel biomaterial features, which can be costly to produce. Practical Implications In this review, we ask why such a limited number of BGs are clinically available when compared to extensive laboratory studies. We also discuss what features are needed for an ideal BG. Results We have identified the key properties of current bone substitutes and have provided important information to guide clinical decision‐making and generate new perspectives on bone substitutes. Our results indicated that different mechanical and biological properties are needed despite each having a broad spectrum of variations. Conclusions We foresee bone replacement composite materials with higher levels of bioactivity, providing an appropriate balance between bioabsorption and volume maintenance for achieving ideal bone remodelling.

Inherently conducting polymers (ICPs) are a specific category of synthetic polymers with distinctive electro-optic properties, which involve conjugated chains with alternating single and double bonds. Polyaniline (PANI), as one of the most well-known ICPs, has outstanding potential applications in biomedicine because of its high electrical conductivity and biocompatibility caused by its hydrophilic nature, low-toxicity, good environmental stability, and nanostructured morphology. Some of the limitations in the use of PANI, such as its low processability and degradability, can be overcome by the preparation of its blends and nanocomposites with various (bio)­polymers and nanomaterials, respectively. This review describes the state-of-the-art of biological activities and applications of conductive PANI-based nanocomposites in the biomedical fields, such as antimicrobial therapy, drug delivery, biosensors, nerve regeneration, and tissue engineering. The latest progresses in the biomedical applications of PANI-based nanocomposites are reviewed to provide a background for future research.

Polylactic acid (PLA)—based polymers are ubiquitous in the biomedical field thanks to their combination of attractive peculiarities: biocompatibility (degradation products do not elicit critical responses and are easily metabolized by the body), hydrolytic degradation in situ, tailorable properties, and well-established processing technologies. This led to the development of several applications, such as bone fixation screws, bioresorbable suture threads, and stent coating, just to name a few. Nanomedicine could not be unconcerned by PLA-based materials as well, where their use for the synthesis of nanocarriers for the targeted delivery of hydrophobic drugs emerged as a new promising application. The purpose of the here presented review is two-fold: on one side, it aims at providing a broad overview of PLA-based materials and their properties, which allow them gaining a leading role in the biomedical field; on the other side, it offers a specific focus on their recent use in nanomedicine, highlighting opportunities and perspectives.

No abstract

Much evidence shows that acute and chronic inflammation in spinal cord injury (SCI), characterized by immune cell infiltration and release of inflammatory mediators, is implicated in development of the secondary injury phase that occurs after spinal cord trauma and in the worsening of damage. Activation of microglia/macrophages and the associated inflammatory response appears to be a self-propelling mechanism that leads to progressive neurodegeneration and development of persisting pain state. Recent advances in polymer science have provided a huge amount of innovations leading to increased interest for polymeric nanoparticles (NPs) as drug delivery tools to treat SCI. In this study, we tested and evaluated in vitro and in vivo a new drug delivery nanocarrier: minocycline loaded in NPs composed by a polymer based on poly-ε-caprolactone and polyethylene glycol. These NPs are able to selectively target and modulate, specifically, the activated proinflammatory microglia/macrophages in subacute progression of the secondary injury in SCI mouse model. After minocycline-NPs treatment, we demonstrate a reduced activation and proliferation of microglia/macrophages around the lesion site and a reduction of cells with round shape phagocytic-like phenotype in favor of a more arborized resting-like phenotype with low CD68 staining. Treatment here proposed limits, up to 15 days tested, the proinflammatory stimulus associated with microglia/macrophage activation. This was demonstrated by reduced expression of proinflammatory cytokine IL-6 and persistent reduced expression of CD68 in traumatized site. The nanocarrier drug delivery tool developed here shows potential advantages over the conventionally administered anti-inflammatory therapy, maximizing therapeutic efficiency and reducing side effects.

)Mi.To. Technology s.r.l., Licensing Department, Viale Vittorio Veneto 2/a, 20124 Milan, Italy T raumatic spinal cord injury (SCI) is an irreversible dramatic event that can incapacitate victims for life. 1À4 Although the incidence is relatively low, the often severe disability that follows and the fact that the victims are often young people, the consequences for the patient is severe and the impact on societal costs is significant. The injury is the result of a primary event due to contusive, compressive, or stretch injury, 1,2,5 followed by the so-called "secondary injury", commonly considered the main cause of the post-traumatic neural degeneration of the cord itself. 6À8 Functional deficits of SCI are caused by different temporal events: spinal cord compression and/or contusion lead to ischemic events that limit both oxygen and glucose contribution to the tissue, with concomitant neuronal cell death, axon damage, and demyelination. 5 Subsequently, glial activation, release of inflammatory factors and cytokines, and scar formation that impedes axons to regrow 8,9 aggravate the progression of the damage.SCI research is following two principal paths. 6,9À11 The first one, already applied in human cases, is based on systemic pharmacological treatments in order to contain side effects (ischemia, free radical release, and inflammation) using neuroprotective drugs (such as corticosteroids) 12À14 and to promote self-regeneration using stimulating factors. 15 The second one relies on tissue engineering 16À18 approaches such as the direct injection of stem cells 19À21 and active agents (drugs, antibodies, and peptides) into the affected area with the aim to bridge the lesion, possibly after removal of the glial scar or reducing endogenous neurite-inhibitory molecules. 22,23 Direct injection of in vitro cultured cells or drugs is the most common choice, but keeping transplanted cells in the lesion area is often desired as transplanted cells readily leave the zone of injection if not confined by any support. To achieve this, a new potential approach is to combine material science with tissue engineering as has been proposed and developed. 16,24À26 In Figure 1 are presented classic tissue engineering approaches as the combination of scaffolds with cells and active agents in order to replace damaged parts of biological tissues. 17,18 In the wide field of biomaterials, increased attention is given to polymers, not only to fabricate three-dimensional scaffolds but also to develop injectable systems for tissue engineering. 26À34 One of the most suitable classes of compounds for these purposes is surely represented by hydrogels. 16,28,31,35À39 These polymers are typically soft and elastic due to their thermodynamic compatibility with water. 16,33,36,40 They can be designed as temporary structures having desired geometry and physical, chemical, and mechanical properties adequate for implantation into chosen target tissue. 6,41À43The aim of this Review is to show the different types of hydrogels used as scaffolds for...

Puropose. Osteoarthritis (OA) is characterized by articular cartilage degeneration and subchondral bone sclerosis. OA can benefit of non-surgical treatments with collagenase-isolated Stromal Vascular Fraction (SVF) or cultured-expanded mesenchymal stem cells (ASCs). To avoid high manipulation of the lipoaspirate needed to obtain ASCs and SVF, we investigated whether articular infusions of autologous concentrated adipose tissue is an effective treatment for knee OA patients.Methods. The knee of 20 OA patients was intra-articularly injected with autologous concentrated adipose tissue, obtained after centrifugation of lipoaspirate. Patients' articular functionality and pain were evaluated by VAS and WOMAC scores ate 3, 6, 18 months from infusion. The osteogenic and chondrogenic ability of ASCs contained in the injected adipose tissue was studied in in vitro primary osteoblast and chondrocyte cell cultures, also plated on 3D-bone scaffold. Knee articular biopsies of patients previously treated with adipose tissue were analyzed. Immunohistochemistry (IHC) and Scanning Electron Microscopy (SEM) were performed to detect cell differentiation and tissue regeneration. Results. The treatment resulted safe, and all patients reported an improvement in terms of pain reduction and increase of function. According to the osteogenic or chondrogenic stimulation, ASCs expressed alkaline phosphatase or aggrecan, respectively. The presence of a layer of newly formed tissue was visualized by IHC staining and SEM. The biopsy of previously treated-knee joints showed new tissue formation, starting from the bone side of the osteochondral lesion. Conclusions. Overall our data indicate that adipose tissue infusion stimulates tissue regeneration and might be considered a safe treatment for knee OA.

Hydrogels are commonly studied for tissue engineering applications and controlled drug delivery. In order to evaluate their reliability as scaffolds and delivery devices, literature describes many release studies performed involving different analytical techniques. However, these experiments can be expensive, time-consuming, and often not reproducible. In this study, two injectable agar-carbomer-based hydrogels were studied, both being loaded with sodium fluorescein, a harmless fluorophore with a steric hindrance similar to many small drugs, such as for example steroids and other neuroprotecting agents. Starting from simple, traditional, and inexpensive release experiments, it was possible to indirectly estimate the self-diffusion coefficient (D) of loaded sodium fluorescein. Such a parameter was also directly measured in the gel matrix by means of high resolution magic angle spinning (HRMAS) diffusion-ordered spectroscopy NMR. Because of the agreement between the calculated values and those measured by HRMAS-NMR spectroscopy, the latter approach can be considered as a simple and fast alternative to long analytic procedures.