The Intraoperative Use of Defensive Antibacterial Coating (DAC®) in the Form of a Gel to Prevent Peri-Implant Infections in Orthopaedic Surgery: A Clinical Narrative Review.

Periprosthetic joint infections (PJIs) in arthroplasty and osteosynthesis-associated infections (OAIs) in reconstructive surgery still represent a challenging complication in orthopaedics and traumatology causing a burden worsening the patient's quality of life, for caregiver and treating physicians, and for healthcare systems. PJIs and OAIs are the result of bacterial adhesion over an implant surface with subsequent biofilm formation. Therefore, the clinical pathological outcome is a difficult-to-eradicate persistent infection. Strategies to treat PJIs and OAIs involve debridement, the replacement of internal fixators or articular prostheses, and intravenous antibiotics. However, long treatments and surgical revision cause discomfort for patients; hence, the prevention of PJIs and OAIs represents a higher priority than treatment. Local antibiotic treatments through coating-release systems are becoming a smart approach to prevent this complication. Hydrophilic coatings, loaded with antibiotics, simultaneously provide a barrier effect against bacterial adhesion and allow for the local delivery of an antibiotic. The intraoperative use of a hyaluronan (HY)-derivative coating in the form of a gel, loaded with antibiotics to prevent PJI, has recently raised interest in orthopaedics. Current evidence supports the use of this coating in the prophylaxis of PJI and IRIs in terms of clinical outcomes and infection reduction. Thus, the purpose of this narrative review is to assess the use of a commercially available HY derivative in the form of a gel, highlighting the characteristics of this biomaterial, which makes it attractive for the management of PJIs and IRIs in orthopaedics and traumatology.

Synthesis and Characterization of a Novel Composite Scaffold Based on Hyaluronic Acid and Equine Type I Collagen.

Herein, the synthesis and characterization of a novel composite biopolymer scaffold-based on equine type I collagen and hyaluronic acid-were described by using a reaction in heterogeneous phase. The resulting biomimetic structure was characterized in terms of chemical, physical, and cytotoxicity properties using human-derived lymphocytes and chondrocytes. Firstly, FT-IR data proved a successful reticulation of hyaluronic acid within collagen structure with the appearance of a new peak at a wavenumber of 1735 cm-1 associated with ester carbonyl stretch. TGA and DSC characterizations confirmed different thermal stability of cross-linked scaffolds while morphological analysis by scanning electron microscopy (SEM) suggested the presence of a highly porous structure with open and interconnected void areas suitable for hosting cells. The enzymatic degradation profile confirmed scaffold higher endurance with collagenase as compared with collagen alone. However, it was particularly interesting that the mechanical behavior of the composite scaffold showed an excellent shape memory, especially when it was hydrated, with an improved Young's modulus of 9.96 ± 0.53 kPa (p ≤ 0.001) as well as a maximum load at 97.36 ± 3.58 kPa compared to the simple collagen scaffold that had a modulus of 1.57 ± 0.08 kPa and a maximum load of 36.91 ± 0.24 kPa. Finally, in vitro cytotoxicity confirmed good product safety with human lymphocytes (viability of 81.92 ± 1.9 and 76.37 ± 1.2 after 24 and 48 h, respectively), whereas excellent gene expression profiles of chondrocytes with a significant upregulation of SOX9 and ACAN after 10 days of culture indicated our scaffold's ability of preserving chondrogenic phenotype. The described material could be considered a potential tool to be implanted in patients with cartilage defects.

Evaluation of a new collagen-based medical device (ElastiCo®) for the treatment of acute Achilles tendon injury and prevention of peritendinous adhesions: An in vitro biocompatibility and in vivo investigation.

Tendon healing still represents a challenge for clinicians because it is slow and incomplete. The most injured is the Achilles tendon, and surgery is the therapeutic strategy often adopted because it provides a quicker functional recovery. Peritendinous adhesions are the main complication of surgery with hyperplasia and chemotaxis of fibroblasts. A biomaterial that blocks fibroblast migration, without interfering with the passage of cytokines and growth factors, might be useful. The present study evaluated the biocompatibility of a new Type I collagen-based scaffold (ElastiCo®) and its ability to promote Achilles tendon healing, inhibiting adhesion formation. After verifying in vitro biocompatibility, physical, and mechanical properties of the scaffold, an in vivo study was performed in 28 rats, operated to induce an acute lesion in both Achilles tendons. One tendon was treated with the suture only and the contralateral one with suture wrapped with ElastiCo® film. After 8 and 16 weeks, it was observed that ElastiCo® reduced internal and external peritendinous adhesions and Collagen III content and increased Collagen I. Elastic modulus increased with both treatments over time. Current results highlighted the clinical translationality of ElastiCo® that could improve the quality of life in patients affected by Achilles tendon lesions surgically treated.

Hydroxyapatite-Based Biomaterials Versus Autologous Bone Graft in Spinal Fusion: An In Vivo Animal Study.

STUDY DESIGN: An in vivo study was designed to compare the efficacy of biomimetic magnesium-hydroxyapatite (MgHA) and of human demineralized bone matrix (HDBM), both dispersed in a mixture of biomimetic MgHA nanoparticles, with that of an autologous bone graft. OBJECTIVE: The objective of this study was to evaluate 2 new bone substitutes as alternatives to a bone autograft for spinal fusion, determining their osteoinductive and osteoconductive properties, and their capacity of remodeling, using a large animal model. SUMMARY OF BACKGROUND DATA: Spinal fusion is a common surgical procedure and it is performed for different conditions. A successful fusion requires potentially osteogenic, osteoinductive, and osteoconductive biomaterials. METHODS: A posterolateral spinal fusion model involved 18 sheep, bilaterally implanting test materials between the vertebral transverse processes. The animals were divided into 2 groups: 1 fusion level was treated with MgHA (group 1) or with HDBM-MgHA (group 2). The other fusion level received bone autografts in both groups. RESULTS: Radiographical, histological, and microtomographic results indicated good osteointegration between the spinous process and the vertebral foramen for both materials. Histomorphometry revealed no significant differences between MgHA and autologous bone for all the parameters examined, whereas significantly lower values of bone volume were observed between HDBM-MgHA and autologous bone. Moreover, the normalization of the histomorphometric data with autologous bone revealed that MgHA showed a significantly higher value of bone volume and a lower value of trabecular number, more similar to autologous bone than HDBM-MgHA. CONCLUSION: The study showed that the use of MgHA in an ovine model of spinal fusion led to the deposition of new bone tissue without qualitative and quantitative differences with respect to new bone formed with autologous bone, whereas the HDBM-MgHA led to a reduced deposition of newly formed bone tissue. LEVEL OF EVIDENCE: N/A.

Long-term results following cranial hydroxyapatite prosthesis implantation in a large skull defect model.

BACKGROUND: A large skull defect may occur after different events such as trauma, tumor resection, and vascular injuries. There is still some doubt about the best material to use for reconstruction. Hydroxyapatite ceramic is one of the materials in use, and its biocompatibility and osteoconductivity are well established. This study evaluated the interaction of a commercial hydroxyapatite custom-made prosthesis implanted in a large skull defect, to assess its osteointegration and its habitability with newly formed bone over time. METHODS: Ten sheep underwent craniectomy and reconstruction of the skull defect with a porous hydroxyapatite cranial prosthesis. The animals were divided into two groups: animals in group A were euthanized after 6 months and animals in group B were euthanized after 12 months. At the end of the experimental periods, each implant was evaluated macroscopically and radiologically, and analyzed by micro-computed tomography, histology, histomorphometry, and microhardness techniques. RESULTS: During the study, no adverse events occurred, and there was no evidence of inflammation or negative tissue reactions. Histology and histomorphometry showed new bone formation inside the implant in both experimental periods; newly formed bone had increased significantly (p < 0.05) by over 300 percent between 6 and 12 months. Three-dimensional micro-computed tomographic analysis showed new bone formation and material remodeling. Microhardness analysis indicated that the mineralization process and the mechanical properties of newly formed bone were not altered. CONCLUSIONS: The hydroxyapatite prosthesis showed its osteoconductivity and good biocompatibility. A low rate of fibrous tissue formation and a high rate of bony regeneration were found.

Orderly osteochondral regeneration in a sheep model using a novel nano-composite multilayered biomaterial.

The objective of this article was to investigate the safety and regenerative potential of a newly developed biomimetic scaffold when applied to osteochondral defects in an animal model. A new multilayer gradient nano-composite scaffold was obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles. In the femoral condyles of 12 sheep, 24 osteochondral lesions were created. Animals were randomized into three treatment groups: scaffold alone, scaffold colonized in vitro with autologous chondrocytes and empty defects. Six months after surgery, the animals were sacrificed and the lesions were histologically evaluated. Histologic and gross evaluation of specimens showed good integration of the chondral surface in all groups except for the control group. Significantly better bone regeneration was observed both in the group receiving the scaffold alone and in the group with scaffold loaded with autologous chondrocytes. No difference in cartilage surface reconstruction and osteochondral defect filling was noted between cell-seeded and cell-free groups. In the control group, no bone or cartilage defect healing occurred, and the defects were filled with fibrous tissue. Quantitative macroscopic and histological score evaluations confirmed the qualitative trends observed. The results of the present study showed that this novel osteochondral scaffold is safe and easy to use, and may represent a suitable matrix to direct and coordinate the process of bone and hyaline-like cartilage regeneration. The comparable regeneration process observed with or without autologous chondrocytes suggests that the main mode of action of the scaffold is based on the recruitment of local cells.

Design of graded biomimetic osteochondral composite scaffolds.

With the ultimate goal to generate suitable materials for the repair of osteochondral defects, in this work we aimed at developing composite osteochondral scaffolds organized in different integrated layers, with features which are biomimetic for articular cartilage and subchondral bone and can differentially support formation of such tissues. A biologically inspired mineralization process was first developed to nucleate Mg-doped hydroxyapatite crystals on type I collagen fibers during their self-assembling. The resulting mineral phase was non-stoichiometric and amorphous, resembling chemico-physical features of newly deposited, natural bone matrix. A graded material was then generated, consisting of (i) a lower layer of the developed biomineralized collagen, corresponding to the subchondral bone, (ii) an upper layer of hyaluronic acid-charged collagen, mimicking the cartilaginous region, and (iii) an intermediate layer of the same nature as the biomineralized collagen, but with a lower extent of mineral, resembling the tidemark. The layers were stacked and freeze-dried to obtain an integrated monolithic composite. Culture of the material for 2 weeks after loading with articular chondrocytes yielded cartilaginous tissue formation selectively in the upper layer. Conversely, ectopic implantation in nude mice of the material after loading with bone marrow stromal cells resulted in bone formation which remained confined within the lower layer. In conclusion, we developed a composite material with cues which are biomimetic of an osteochondral tissue and with the capacity to differentially support cartilage and bone tissue generation. The results warrant testing of the material as a substitute for the repair of osteochondral lesions in orthotopic animal models.

ACP gel: a new hyaluronic acid-based injectable for facial rejuvenation. Preclinical data in a rabbit model.

BACKGROUND: Facial aging results from reduced biosynthetic activity of dermal fibroblasts and decreased deposition of extracellular matrix components, such as hyaluronic acid, a glycosaminoglycan responsible for skin hydration and turgidity. Exogenous hyaluronic acid injections provide a safe though short-term solution for facial rejuvenation. Using a rabbit model, the authors investigated residence time and tolerability of ACP gel, a new hyaluronic acid cross-linked derivative, compared with high-molecular-weight native hyaluronic acid currently used for facial rejuvenation (Ial System). METHODS: ACP gel 1% and 2%, Ial System, and saline were intradermally injected into the backs of 12 New Zealand rabbits: six animals were used to follow volume maintenance and redness up to 10 days and the other six animals were euthanized at days 2, 6, 8, 10, 14, and 21 (one animal per time point) to histologically assess biocompatibility. RESULTS: ACP gel 2% had the longest residence time, showing a significantly better volume maintenance than the other samples, especially in the initial study period (71 percent of original volume versus 23 percent and 21 percent of ACP gel 1% and Ial System, respectively, at day 2). Macroscopically, no adverse events were observed in the treated animals. Histologic examination confirmed the absence of adverse events, persistent inflammation, tissue degeneration, or necrosis. ACP gel macrophage-mediated phagocytosis was more persistent with respect to the Ial System, consistent with its longer residence time. CONCLUSION: ACP gel 2% is a promising dermal biorevitalizer, characterized by a high safety profile and prolonged residence time in relation to native high-molecular-weight hyaluronic acid.

Pharmacokinetic behaviour of ACP gel, an autocrosslinked hyaluronan derivative, after intraperitoneal administration.

Autocrosslinked polysaccharide (ACP) gel is a fully biocompatible cross-linked derivative of hyaluronic acid, which has prolonged in vivo residence time and improved mechanical properties with respect to native hyaluronan for use in various surgical applications. The objective of this study was to assess the pharmacokinetic behaviour of ACP gel in dogs after intraperitoneal administration. Seven beagle dogs received intraperitoneal injections of tritium-labelled ACP gel. Blood samples were taken, and urine and faeces were collected until sacrifice, scheduled at various time points from 3 to 192 h after administration. Organs were removed from the animals at autopsy. Bodily fluid and organ samples were analysed for total and non-volatile radioactivity. Non-volatile radioactivity slowly appeared in plasma, with a median T(max) of 12 h, and then declined with a mean half-life of 69 h. Total radioactivity in plasma peaked later and declined more slowly, consistent with the formation of tritiated water. Little non-volatile radioactivity was found in any organs except the liver, where about 16% of the dose was present 72 h after administration, and the intestines, where the presence of radioactivity was probably due to a retention effect. A minor amount of non-volatile radioactivity was also found in the bone marrow. In summary, ACP gel administered into the peritoneal cavity is removed slowly by active initial catabolism at the injection site, and is then catabolised by well described physiological pathway of hyaluronan degradation with final release of simple molecules such as CO(2) and H(2)O. Given its in vivo residence time, ACP gel may be considered an ideal implantable surgical device.