The morbidity of bone fractures and defects is steadily increasing due to changes in the age pyramid. As such, novel biomaterials that are able to promote the healing and regeneration of injured bones are needed in order to overcome the limitations of auto-, allo-, and xenografts, while providing a ready-to-use product that may help to minimize surgical invasiveness and duration. In this regard, recombinant biomaterials, such as elastin-like recombinamers (ELRs), are very promising as their design can be tailored by genetic engineering, thus allowing scalable production and batch-to-batch consistency, amongst others. Furthermore, they can self-assemble into physically cross-linked hydrogels above a certain transition temperature, in this case body temperature, but are injectable below this temperature, thereby markedly reducing surgical invasiveness. Herein we have developed two bioactive hydrogel-forming ELRs, one including the osteogenic and osteoinductive BMP-2 and the other the RGD cell-adhesion motif. The combination of these two novel ELRs results in a BMP-2-loaded extracellular matrix-like hydrogel. Moreover, elastase-sensitive domains were included in both ELR molecules, thereby conferring biodegradation as a result of enzymatic cleavage and avoiding the need for scaffold removal after bone regeneration. Both ELRs and their combination showed excellent cytocompatibility, and the culture of cells on RGD-containing ELRs resulted in optimal cell adhesion. In addition, hydrogels based on a mixture of both ELRs were implanted in a pilot study involving a femoral bone injury model in New Zealand White rabbits, showing complete regeneration in six out of seven cases, with the other showing partial closure of the defect. Moreover, bone neo-formation was confirmed using different techniques, such as radiography, computed tomography and histology. This hydrogel system therefore displays significant potential in the regeneration of bone defects, promoting self-regeneration by the surrounding tissue with no involvement of stem cells or osteogenic factors other than BMP-2, which is released in a controlled manner by elastase-mediated cleavage from the ELR backbone.

The increase in fracture rates and/or problems associated with missing bones due to accidents or various pathologies generates socio-health problems with a very high impact. Tissue engineering aims to offer some kind of strategy to promote the repair of damaged tissue or its restoration as close as possible to the original tissue. Among the alternatives proposed by this specialty, the development of scaffolds obtained from recombinant proteins is of special importance. Furthermore, science and technology have advanced to obtain recombinant chimera’s proteins. This review aims to offer a synthetic description of the latest and most outstanding advances made with these types of scaffolds, particularly emphasizing the main recombinant proteins that can be used to construct scaffolds in their own right, i.e., not only to impregnate them, but also to make scaffolds from their complex structure, with the purpose of being considered in bone regenerative medicine in the near future.

Extensive bone defect healing is an important health issue not yet completely resolved. Different alternative treatments have been proposed but, in face of a critical bone defect, it is still very difficult to reach a complete regeneration, with the new-formed bone presenting all morphological and physiological characteristics of a normal, preinjury bone. Topical melatonin use has shown as a promising adjuvant for bone regeneration due to its positive effects on bone metabolism. Thus, to search for new, safe, biological techniques that promote bone repair and favor defect healing, we hypothesized that there is a synergistic effect of melatonin treatment associated with rhBMP-2 to guide bone regeneration. This study aimed to investigate bone repair effects of topical melatonin administration in different concentrations (1, 10, and 100 µg), associated or not with rhBMP-2. Surgical-induced bone defect healing was qualitatively evaluated through histopathological analysis by light microscopy. Additionally, quantitative stereology was performed in immunohistochemistry-prepared tissue to identify angiogenic, osteogenic, and osteoclastogenic factors. Quantification data were compared between groups by the ANOVA/Tukey test and differences were considered significant when p < 0.05. Our results showed that the presence of the scaffold in the bone defect hindered the process of bone repair because in the group treated with “blood clot + scaffold” the results of bone formation and immunolabeling were reduced in comparison with all other groups (treated with melatonin alone or in association with rhBMP-2). Statistical analysis revealed a significant difference between the control group (bone defect + blood clot), and groups treated with different concentrations of melatonin in association with rhBMP-2, indicating a positive effect of the association for bone repair. This treatment is promising once it becomes a new safe alternative technique for the clinical treatment of fractures, bone defects, and bone grafts. Our results support the hypothesis of the safe use of the association of melatonin and rhBMP-2 and have established a safe and effective dose for this experimental treatment.

Background/Objectives: Chronic exposure to stress has been considered a risk factor for hypertension, which is also associated with increased bone resorption. This review aimed to investigate the effect of acute and chronic stress, associated with hypertension, on the skeletal system. Methods: A comprehensive search was conducted across multiple databases, focusing on peer-reviewed articles published in English. We include experimental, clinical, and peer-reviewed studies focused on the relationship between stress, hypertension, and bone resorption. Searches were conducted in MEDLINE via PubMed, Embase and Scopus, with the last search completed on 10 September 2024. Results: The main topics include situations that favor bone loss, such as psychological stress, which can lead to osteoporotic fractures through immunological and endocrine mechanisms. The relationship between psychological stress and loss of bone density, as in osteoporosis, occurs due to the reduction in the number of osteoblasts and loss in the balance between physiological formation/resorption. Conclusions: Chronic stress significantly affects cardiovascular health and bone resorption. This narrative review study highlights the vulnerability of the skeletal system, along with the cardiovascular system, to prolonged stress, emphasizing the need for multidisciplinary strategies in preventing stress-related conditions. Effective stress management can help reduce the risks of cardiovascular disease and bone resorption, emphasizing their role in comprehensive health care.

Large bone defects are a significant health problem today with various origins, including extensive trauma, tumours, or congenital musculoskeletal disorders. Tissue engineering, and in particular bone tissue engineering, aims to respond to this demand. As such, we propose a specific model based on Elastin-Like Recombinamers-based click-chemistry hydrogels given their high biocompatibility and their potent on bone regeneration effect conferred by different bioactive sequences. In this work we demonstrate, using biochemistry, histology, histomorphometry and imaging techniques, the biocompatibility of our matrix and its potent effect on bone regeneration in a model of bone parietal lesion in female New Zealand rabbits.

Background: The biomaterials engineering goal is to manufacture a biocompatible scaffold that adequately supports or improves tissue regeneration after implantation of the biomaterial in the injured area. Many requirements are demanded for a biomaterial, such as biocompatibility, elasticity, degradation time, and a very important factor is its cost of importation or synthesis, making its application inaccessible to some countries. Studies about biomaterials market show that Polylactic acid (PLLA) is one of the most used polymers, but expensive to produce. It becomes important to prove the biocompatibility of the new PLLA and to find strategies to produce biocompatible biopolymers at an acceptable production cost. Methods: In this work, the polylactic acid biomaterial was synthesized by ring-opening polymerization. The polymer was submitted to initial in vivo biocompatibility studies in 12 New Zealand female rabbits, assigned to two groups: (1) Lesion and PLLA group (n = 6), (2) Lesion No PLLA group (n = 6). Each group was divided into two subgroups at six and nine months post-surgical time. Before euthanasia clinical and biochemical studies were performed and after that tomographic (CT), histological (Hematoxylin and Eosin and Masson's trichrome) and histomorphometric analyses were performed to evaluate the injury site and prove biocompatibility. The final cost of this polymer was analyzed. Results: The statistical studies of hemogram and hepatocyte enzymes, showed that there were no significant differences between the groups for any of the times studied, in any of the variables considered and the results of CT and histology showed that there was an important process of neoregeneration. The cost analysis showed the biopolymer synthesis is between R$3,06 - R$5,49 cheaper than the import cost. Conclusions: It was possible to synthesize the PLLA biopolymer by cyclic ring opening, which proved to be biocompatible, potential osteoregenerative and cheaper than other imported biopolymers.