Cartilage Healing Research Articles

Application of Alginate Hydrogels for Next-Generation Articular Cartilage Regeneration.

The articular cartilage has insufficient intrinsic healing abilities, and articular cartilage injuries often progress to osteoarthritis. Alginate-based scaffolds are attractive biomaterials for cartilage repair and regeneration, allowing for the delivery of cells and therapeutic drugs and gene sequences. In light of the heterogeneity of findings reporting the benefits of using alginate for cartilage regeneration, a better understanding of alginate-based systems is needed in order to improve the approaches aiming to enhance cartilage regeneration with this compound. This review provides an in-depth evaluation of the literature, focusing on the manipulation of alginate as a tool to support the processes involved in cartilage healing in order to demonstrate how such a material, used as a direct compound or combined with cell and gene therapy and with scaffold-guided gene transfer procedures, may assist cartilage regeneration in an optimal manner for future applications in patients.

Effect analysis of iliac bone autografting for Hepple V osteochondral lesions of the talus

BackgroundTalar cartilage injury is a kind of disease that causes long-term and chronic pain of ankle joint. Autologous osteochondral transplantation has been viewed as an alternative choice for treating these lesions, but donor-site morbidity has limited its application. This study aimed to analyze the efficacy of iliac bone autografting for Hepple V osteochondral lesions of the talus.MethodsThis retrospective study included 32 patients surgically treated for Hepple V osteochondral lesions of the talus from January 2015 to January 2020. All patients underwent open surgery. Ipsilateral iliac bone grafts were taken and filled with talar cartilage injury area. The improvement of postoperative ankle pain was evaluated by Visual Analogue Scale (VAS), and the improvement of ankle function was evaluated by the American Orthopaedic Foot & Ankle Society (AOFAS). During the postoperative follow-up, X-ray examination of the front and side of the ankle joint and CT of the ankle joint were performed to evaluate the bone cartilage healing in the graft area.ResultsThirty-two patients (32 ankles) (100%) returned for clinical and radiologic follow-up at an average of 28 (range 24–36) months postoperatively. At 3 months postoperatively and at the last follow-up, the AOFAS scores were (80.4 ± 3.6) and (89.2 ± 6.4), respectively, which were significantly improved compared with the preoperative score (49.7 ± 8.1), and the difference was statistically significant (P < 0.05). The VAS scores were (2.1 ± 0.9) and (1.5 ± 0.8), respectively, which were significantly better than the preoperative score (6.2 ± 1.7), and the difference was statistically significant (P < 0.05). Re-examination of the front and side of the ankle joint X-rays and CT showed that the bone healing at the osteotomy of medial malleolus and osteochondral transplantation area. All patients had no pain at the donor site. No complications occurred in 32 patients at the last follow-up.ConclusionsWith iliac bone autografting for Hepple V osteochondral lesions of the talus can effectively relieve ankle joint pain and significantly improved ankle function.Level of evidenceLevel III, Retrospective series.

Reliability of the novel MRI-based OCD lesion healing assessment tool for adolescent OCD of the knee

BACKGROUND: One of the most debatable issues in osteochondritis dissecans (OCD) research is bone and cartilage healing assessment during OCD postoperative management. The x-ray scale developed by Wall and colleagues is a commonly used evaluation tool for OCD lesion assessment. This tool has excellent reliability but is associated with radiologic exposure. Also, it provides complete information about bone structure only, even though the articular cartilage is also involved in the pathological process. Lack of cartilage assessment combined with radiation exposure facilitated the development of the novel MRI-based OCD healing assessment tool. It could draw attention to bone and cartilage during healing assessment to improve decision-making in the postoperative period after OCD treatment.&#x0D; AIM: This study assesses the reliability of a developed novel MRI-based OCD healing assessment tool.&#x0D; MATERIALS AND METHODS: Ten patients with OCD of the femoral condyle were involved in the current study. A reliability test for the novel MRI-based assessment tool was performed with the expert group comprising six participants to assess 34 MRI studies of 10 patients. From all studies, one study was obligatory for each patient before the operative treatment, and a postoperative MRI study series was performed during the first postoperative year. Each MRI study was examined by each expert twice with a 4-week time lag. The novel MRI-based assessment tool consists of five criteria, of which the common criterion was general healing, incorporating all previously described ones. Each criterion was tested, and a two-way mixed-effects intraclass correlation coefficient (ICC) was used to assess intraobserver and interobserver reliability.&#x0D; RESULTS: The main parameter general healing calculations were made first. Two patients achieved full OCD lesion healing with 100 scale points and two patients with 97.5 and 98.5 points, respectively. Other patients reached the cut-off value of 75 points and were defined as healed with minimally detectable changes on MRI. Second, a two-way mixed-effects ICC calculation was performed. The bone marrow extension parameter reached the value of 0.972, the extent of the union 0.984, bone structure 0.977, and articular cartilage intensity and structure 0.977. The general healing parameter reached the value of 0.993. These values corresponded to the excellent marks according to the guidelines for ICC assessment. The novel MRI-based assessment tool showed excellent intraobserver and interobserver reliability.&#x0D; CONCLUSIONS: The novel MRI-based assessment tool permits assessing bony and cartilage structures while making decisions about OCD lesion healing in the postoperative period. The novel OCD healing assessment tool has excellent intraobserver and interobserver reliability. Also, it is recommended for use in clinical and research practice since a study revealed a correlation of the MRI healing score with that of the clinical assessment tool.

Magnetic Resonance Imaging Assessment of Cartilage Appearance Following Marrow Stimulation of Osteochondritis Dissecans of the Humeral Capitellum

Osteochondritis dissecans (OCD) of the capitellum is often treated by marrow stimulation techniques with good long-term outcomes. Magnetic resonance imaging (MRI) can be used to characterize the healing of cartilage repair tissue. However, no formal system exists for assessment of cartilage healing after marrow stimulation in capitellar OCD. The aims of this study were to describe the postoperative MRI appearance of capitellar repair cartilage after debridement and marrow stimulation for capitellar OCD and assess differences between symptomatic and asymptomatic patients. This was a retrospective study of patients with capitellar OCD who underwent arthroscopic debridement and marrow stimulation and had a postoperative MRI to assess healing. The classification system developed by Marlovits and colleagues (Magnetic Resonance Observation of Cartilage Repair Tissue) was used to quantitatively profile the cartilage repair tissue in comparison to adjacent "normal" cartilage. Study participants completed an online survey to correlate outcomes with cartilage appearance. Eleven patients who underwent MRI for routine evaluation (asymptomatic), and 18 who underwent MRI for symptoms were identified. Overall, 59% of defects were completely filled, and in 83%, the cartilage surface had ulcerations or fibrillations. The cartilage variables were similar between symptomatic and asymptomatic patients. Capitellar subchondral bone edema was observed on the MRI of every patient who underwent a reoperation and was present in only 62% of those who did not. Clinical scores did not correlate with MRI cartilage findings, but the small sample size limited conclusions regarding clinical outcomes related to postoperative cartilage features seen on MRI. This detailed assessment of cartilage appearance by MRI after marrow stimulation for capitellar OCD demonstrated that incomplete cartilage fill was common in both symptomatic and asymptomatic patients. Those requiring a second surgery were more likely to demonstrate subchondral bone edema. Diagnostic IV.

VEGF-attenuated platelet-rich plasma improves therapeutic effect on cartilage repair.

Autologous platelet-rich plasma (PRP) has gained popularity as a less invasive treatment for various musculoskeletal tissue injuries and conditions due to its favorable safety profile, minimal manipulation and cost-effectiveness. Although PRP treatment has been clinically used for the treatment of osteoarthritis (OA) and damaged cartilage, evidence on therapeutic efficacy has been inconsistent, which calls for a methodology to achieve consistent and improved treatment outcomes. Given that PRP contains numerous proteins, we hypothesized that attenuation of a growth factor known to be detrimental to the healing tissue would enhance efficacy of PRP treatment. Considering that VEGF-mediated angiogenesis inhibits the repair of articular cartilage, we developed VEGF-attenuated PRP by sequestering VEGF in PRP using VEGF-binding microspheres. We demonstrated that VEGF attenuation in PRP did not inhibit the effect of PRP on chondrogenic differentiation of stem cells in vitro. In addition, healing of rat OA cartilage was significantly improved after treatment with VEGF-attenuated PRP when compared to the PRP treatment group or PBS control group. We expect that attenuation of unwanted biological activity using growth factor-binding microspheres could provide a new PRP customization method broadly applicable to various tissue repair processes.

The Morphological, Clinical and Radiological Outputs of the Preclinical Study After Treatment of the Osteochondral Lesions in the Porcine Knee Model Using Implantation of Scaffold Based on the of Calcium Phosphate Biocement

The symptomatic full-thickness cartilage lesions or cartilage degeneration leads to the destruction of the normal chondral architecture and bone structure in affected area, causes the osteoarthritis, and general damage to the health. Knee joints are most frequently affected by this condition. The permanent damage of the articular cartilage and subchondral bone has motivated many scientists and clinicians to explore new methods of regeneration of osteochondral defects, such as novel materials.We studied the potential of the biocement based on calcium phosphate consisting of a mixture of four amino acids (glycine, proline, hydroxyproline and lysine) in the regenerating process of the artificially created osteochondral defect on the porcine medial femoral condyle in the stifle joint. The mass ratio of the amino acids in biocement CAL was 4:2:2:1. The Ca/P ratio in cement was 1.67 which correspond with ratio in hydroxyapatite. We compared the results with spontaneous healing of an artificially created cyst with that of the healthy tissue. The animal group treated with biocement paste CAL presented completely filled osteochondral defects. The results were confirmed by histological and radiological assessments, which have shown regenerated chondral and bone tissue in the examined knee joints. Macroscopic evaluation showed that neocartilage was well integrated with the adjacent native cartilage in animal group with biocement CAL, compared with healing of the artificial cyst, where treated cartilage surfaces were visibly lower than the surrounding native cartilage surface and a border between native and restored tissue was apparent. The qualitative assessment of the implant histology specimens showed full regeneration of the hyaline cartilage and subchondral bone in animals with biocement CAL. The artificial cyst group showed remarkable fibrillation. The detailed MRI analysis of cross-section of osteochondral defect confirmed the complete cartilage and subchondral bone healing where the thickness of the regenerated cartilage was 1.5 mm. The MRI imaging of defects in the artificial cyst group showed incomplete healing, neo cartilage tissue reduced up to 50%.

Migratory chondroprogenitors retain superior intrinsic chondrogenic potential for regenerative cartilage repair as compared to human fibronectin derived chondroprogenitors

Cell-based therapy for articular hyaline cartilage regeneration predominantly involves the use of mesenchymal stem cells and chondrocytes. However, the regenerated repair tissue is suboptimal due to the formation of mixed hyaline and fibrocartilage, resulting in inferior long-term functional outcomes. Current preclinical research points towards the potential use of cartilage-derived chondroprogenitors as a viable option for cartilage healing. Fibronectin adhesion assay-derived chondroprogenitors (FAA-CP) and migratory chondroprogenitors (MCP) exhibit features suitable for neocartilage formation but are isolated using distinct protocols. In order to assess superiority between the two cell groups, this study was the first attempt to compare human FAA-CPs with MCPs in normoxic and hypoxic culture conditions, investigating their growth characteristics, surface marker profile and trilineage potency. Their chondrogenic potential was assessed using mRNA expression for markers of chondrogenesis and hypertrophy, glycosaminoglycan content (GAG), and histological staining. MCPs displayed lower levels of hypertrophy markers (RUNX2 and COL1A1), with normoxia-MCP exhibiting significantly higher levels of chondrogenic markers (Aggrecan and COL2A1/COL1A1 ratio), thus showing superior potential towards cartilage repair. Upon chondrogenic induction, normoxia-MCPs also showed significantly higher levels of GAG/DNA with stronger staining. Focused research using MCPs is required as they can be suitable contenders for the generation of hyaline-like repair tissue.

Advances in Use of Nanomaterials for Musculoskeletal Regeneration.

Since the worldwide incidence of bone disorders and cartilage damage has been increasing and traditional therapy has reached its limits, nanomaterials can provide a new strategy in the regeneration of bones and cartilage. The nanoscale modifies the properties of materials, and many of the recently prepared nanocomposites can be used in tissue engineering as scaffolds for the development of biomimetic materials involved in the repair and healing of damaged tissues and organs. In addition, some nanomaterials represent a noteworthy alternative for treatment and alleviating inflammation or infections caused by microbial pathogens. On the other hand, some nanomaterials induce inflammation processes, especially by the generation of reactive oxygen species. Therefore, it is necessary to know and understand their effects in living systems and use surface modifications to prevent these negative effects. This contribution is focused on nanostructured scaffolds, providing a closer structural support approximation to native tissue architecture for cells and regulating cell proliferation, differentiation, and migration, which results in cartilage and bone healing and regeneration.

Therapeutic Role of Platelet Rich Plasma in Formaldehyde-Induced Arthritis in Adult Male Albino Rats

Abstract Introduction Osteoarthritis (OA) is a common health problem. Platelet-rich plasma (PRP) has been recognized to enhance articular cartilage metabolism. Aim of the work the study was designed to investigate the influence of PRP on cartilage healing after induction of arthritis. Material and methods Forty two adult male albino rats were used in this study. The rats were randomly divided into three groups: Group I (n = 18): the control group (Ia, Ib &amp; Ic) Ib &amp; Ic were injected intra-articularly with saline and left for 3 and 6 weeks. Group II (n = 12): arthritic group, in which osteoarthritis was induced by injection of 0.02ml 5% formaldehyde once in the right knee joints, left without treatment, and were sacrificed after three weeks (IIa) or after six weeks (IIb). Group III(n = 12): arthritis was induced as group II, one week later, the rats were intra-articularly injected with single dose of 0.3ml PRP in the same joint then were sacrificed three weeks (IIIa) or six weeks (IIIb) after formaldehyde injection. At the end of the study the right knee joints were taken, decalcified then processed for paraffin sections to be examined by light microscope using H&amp;E, toluidine blue and Masson’s trichrome (MTC) stains. Immunohistochemistry for caspase-3 enzyme was done to demonstrate apoptotic chondrocytes. Morphometric study was conducted to measure the thickness of the non-calcified cartilage, count the chondrocytes and synovial membrane inflammatory cells and Mankin's score. Then statistical analysis was done. Results The arthritic groups revealed irregular surface of the articular cartilage, loss of the articular matrix and bone eburnation. Moreover, there was apparent hypocellularity and disorganization of the chondrocytes. Osteoclasts and osteoblasts were seen invading the osteochondral junction. MTC stained sections of the synovial membrane showed deposition of thick collagen bundles with heavy inflammatory cell infiltrate and numerous blood vessels. The affinity of the articular cartilage to toluidine blue stain was apparently decreased while caspase-3 immunoreactivity was apparent in many chondrocytes .Group IIIa demonstrated almost similar histological findings as the control group; regular articular cartilage surface with regularly arranged chondrocytes in the different cartilage zones. Synovial membrane illustrated minimal inflammatory cell infiltrate with thin collagen bundles and small blood vessels in MTC stained sections. There was high affinity of the articular cartilage to the toluidine blue stain and few chondrocytes showed positive caspase-3 immunoreactivity. Group IIIb revealed continuous surface of the articular cartilage, yet with minimal fibrillation in some areas. Osteoblasts and osteoclasts were seen invading the calcified cartilage. Synovial membrane showed deposition of dense collagen bundles with some inflammatory cell infiltrate. Toluidine blue sections revealed decreased articular cartilage affinity to the stain while caspase-3 immunoreactivity was evident in many chondrocytes. The morphometric results and statistical analysis confirmed the histological findings. Conclusion Intra-articular injection of PRP demonstrated advantageous role on articular cartilage healing, however, these effects appeared to be transient. So the need of multiple injections of PRP has to be considered in cases of OA.

The use of a novel deer antler decellularized cartilage-derived matrix scaffold for repair of osteochondral defects

BackgroundThe physiologic regenerative capacity of cartilage is severely limited. Current studies on the repair of osteochondral defects (OCDs) have mainly focused on the regeneration of cartilage tissues. The antler cartilage is a unique regenerative cartilage that has the potential for cartilage repair.MethodsAntler decellularized cartilage-derived matrix scaffolds (adCDMs) were prepared by combining freezing-thawing and enzymatic degradation. Their DNA, glycosaminoglycans (GAGs), and collagen content were then detected. Biosafety and biocompatibility were evaluated by pyrogen detection, hemolysis analysis, cytotoxicity evaluation, and subcutaneous implantation experiments. adCDMs were implanted into rabbit articular cartilage defects for 2 months to evaluate their therapeutic effects.ResultsAdCDMs were observed to be rich in collagen and GAGs and devoid of cells. AdCDMs were also determined to have good biosafety and biocompatibility. Both four- and eight-week treatments of OCDs showed a flat and smooth surface of the healing cartilage at the adCDMs filled site. The international cartilage repair society scores (ICRS) of adCDMs were significantly higher than those of controls (porcine dCDMs and normal saline) (p < 0.05). The repaired tissue in the adCDM group was fibrotic with high collagen, specifically, type II collagen.ConclusionsWe concluded that adCDMs could achieve excellent cartilage regeneration repair in a rabbit knee OCDs model. Our study stresses the importance and benefits of adCDMs in bone formation and overall anatomical reconstitution, and it provides a novel source for developing cartilage-regenerating repair materials.

Arthroscopic utilization of ChondroFiller gel for the treatment of hip articular cartilage defects: a cohort study with 12- to 60-month follow-up.

ChondroFiller gel is an absorbable collagen implant. It serves as a protective cover for the cartilage defects, allowing chondrocyte migration into the lesion. The implant consists of collagen (Type I) and is derived from veterinary monitored rats. This study evaluates the use of ChondroFiller gel in the treatment of cartilage lesions during hip joint arthroscopy. A prospective study was conducted on a group of 26 adult patients. All patients had an existing femoroacetabular impingement together with acetabular cartilage lesions >2 cm2. All patients underwent hip arthroscopic surgery and the lesions were treated using ChondroFiller gel. The cartilage tissue healing was evaluated postoperatively using MRI. A total of 26 patients, including 5 females and 21 males, all with articular cartilage lesions, were included in the study. Cartilage healing conditions were evaluated for all patients, and the difference between pre- and post-surgery conditions was statistically significant. The follow-up scores have been acquired from 21 out of initial 26 patients (2 were disqualified after receiving THR, 3 could not be reached by researchers) after 3, 4 and 5 years consecutively with 17/21 patients having good/excellent results. The use of ChondroFiller gel during arthroscopy of the hip for acetabular cartilage lesions is an effective treatment technique. Encouraging long-term results have been observed, but further research on larger group of patient is required to better assess the full value of this technique. Patients with pre-existing osteoarthritis (Tönnis 2–3) have poor results.

Effect of concurrent repair of medial meniscal posterior root tears during high tibial osteotomy for medial osteoarthritis during short-term follow-up: a systematic review and meta-analysis

BackgroundMedial meniscal posterior root tears (MMPRTs) are frequently associated with medial compartment osteoarthritis, leading to loss of meniscal hoop tension. This study aimed to evaluate the efficacy of concurrent MMPRT repair during high tibial osteotomy (HTO) compared to HTO alone in patients with medial osteoarthritis and MMPRTs.MethodsThe MEDLINE/PubMed, EMBASE, and Cochrane Library databases were searched for studies reporting on concurrent MMPRT repair during HTO. Pre- and postoperative data were pooled to investigate the treatment effects of concurrent MMPRT repair during HTO, and compare postoperative clinical, radiological, and arthroscopic outcomes including cartilage status and healing event rates according to the arthroscopic classification of MMPRT healing (complete, partial [lax or scar tissue], or failed healing) between HTO patients with and without concurrent MMPRT repair. The random-effect model was used to pool the standardized mean differences, odds ratios (ORs), 95% confidence intervals (CIs), and event rates.ResultsSeven patient subgroups in six articles divided according to meniscal repair techniques were included in the final analysis. Concurrent MMPRT repair during HTO significantly improved the Lysholm score, while no intergroup differences were observed in the postoperative Lysholm and WOMAC scores, as well as radiological and arthroscopic outcomes. Those who underwent concurrent MMPRT repair showed a higher rate of complete meniscal healing (OR: 4.792, 95% CI, 1.95–11.79), with a pooled rate of complete meniscal healing of 0.327 (95% CI, 0.19–0.46).ConclusionConcurrent MMPRT repair during HTO for medial osteoarthritis with MMPRTs has little benefits on the clinical, radiological, and arthroscopic outcomes during short-term follow-up. Further accumulation of evidence is needed for long-term effects.

Parathyroid hormone promotes cartilage healing after free reduction of mandibular condylar fractures by upregulating Sox9.

After high fractures of the mandibular condyle, the insufficient blood supply to the condyle often leads to poor bone and cartilage repair ability and poor clinical outcome. Parathyroid hormone (PTH) can promote the bone formation and mineralization of mandibular fracture, but its effects on cartilage healing after the free reduction and internal fixation of high fractures of the mandibular condyle are unknown. In this study, a rabbit model of free reduction and internal fixation of high fractures of the mandibular condyle was established, and the effects and mechanisms of PTH on condylar cartilage healing were explored. Forty-eight specific-pathogen-free (SPF) grade rabbits were randomly divided into two groups. In the experimental group, PTH was injected subcutaneously at 20 µg/kg (PTH (1-34)) every other day, and in the control group, PTH was replaced with 1 ml saline. The healing cartilages were assessed at postoperative days 7, 14, 21, and 28. Observation of gross specimens, hematoxylin eosin staining and Safranin O/fast green staining found that every-other-day subcutaneous injection of PTH at 20 µg/kg promoted healing of condylar cartilage and subchondral osteogenesis in the fracture site. Immunohistochemistry and polymerase chain reaction showed that PTH significantly upregulated the chondrogenic genes Sox9 and Col2a1 in the cartilage fracture site within 7-21 postoperative days in the experimental group than those in the control group, while it downregulated the cartilage inflammation gene matrix metalloproteinase-13 and chondrocyte terminal differentiation gene ColX. In summary, exogenous PTH can stimulate the formation of cartilage matrix by triggering Sox9 expression at the early stage of cartilage healing, and it provides a potential therapeutic protocol for high fractures of the mandibular condyle.

Topical Review: Bone Marrow Aspirate Concentrate and Its Clinical Use in Foot and Ankle Surgery.

Bone marrow aspirate concentrate (BMAC) is now commonly used in orthopedic surgery. Animal studies showed promising results for cartilage, bone, and soft tissue healing; however, many of these outcomes have yet to be translated to human models. While there has been an increase in the use of BMAC in foot and ankle procedures, the associated clinical evidence is limited. The purpose of this review is to analyze the existing literature in order to evaluate the safety and efficacy of BMAC in foot and ankle surgery.

Should Isotretinoin be Stopped Prior to Surgery?

Should Isotretinoin be Stopped Prior to Surgery?

Tissue Engineering Scaffold Materials to Repair Sports Cartilage Injury

With the continued development of sports in China, sports sometimes cause cartilage damage. The purpose of this research is to study the tissue engineering scaffold material for sports cartilage damage repair. In this study, mesenchymal rat bone marrow stem cells (to put it simply, stem cells are a type of cell with unlimited or immortal self-renewal capacity, capable of producing at least one type of highly differentiated progeny cells) were obtained by the total bone wash method. The cells were inoculated into the cell culture bottle. When the primary cultured cells proliferated to about 80% of the culture bottle area, the cells were digested with trypsin to open the cell link, then the medium containing 10% serum was added to terminate the cell digestion, and then the passage expansion was carried out according to the cell density. PLGA/NHA and PLGA were heated to 65°C under ultrasonic vibration until uniform PLGA/NHA and PLGA solutions were obtained. Then, the samples were added to the tube mold and then heated and cooled to obtain the composite porous scaffold of mesenchymal stem cells. 10 μl MSCs cell suspension was extracted with a microinjector, and the needle was injected from the inside of the scaffold, and the cell suspension was added outside the scaffold to ensure that there were composite cells inside and outside the scaffold. The subcutaneous tissue of the skin was cut along the medial side of the knee joint and the capsule of the switch segment was cut. The scaffold materials were filled into the osteochondral defect to observe the cartilage healing. The mechanical strength of 0.5% PLGA-MSCs composite porous scaffold was increased to 1.1 MPa, and the cell density was high. The repair of cartilage in rats was the best. The results showed that the porous scaffolds designed in this study have good compatibility and are beneficial to repair sports cartilage injury.

Microfracture Augmentation With Trypsin Pretreatment and Growth Factor–Functionalized Self-assembling Peptide Hydrogel Scaffold in an Equine Model

Background: Microfracture augmentation can be a cost-effective single-step alternative to current cartilage repair techniques. Trypsin pretreatment combined with a growth factor–functionalized self-assembling KLD hydrogel (“functionalized hydrogel”) has been shown to improve overall cartilage repair and integration to surrounding tissue in small animal models of osteochondral defects. Hypothesis: Microfracture combined with trypsin treatment and a functionalized hydrogel will improve reparative tissue quality and integration as compared with microfracture alone in an equine model. Study Design: Controlled laboratory study. Methods: Bilateral cartilage defects (15-mm diameter) were created on the medial trochlear ridge of the femoropatellar joints in 8 adult horses (16 defects total). One defect was randomly selected to receive the treatment, and the contralateral defect served as the control (microfracture only). Treatment consisted of 2-minute trypsin pretreatment of the surrounding cartilage, subchondral bone microfracture, and functionalized hydrogel premixed with growth factors (platelet-derived growth factor and heparin-binding insulin-like growth factor 1). After surgery, all horses were subjected to standardized controlled exercise on a high-speed treadmill. Clinical evaluation was conducted monthly, and radiographic examinations were performed at 2, 16, 24, 32, 40, and 52 weeks after defect creation. After 12 months, all animals were euthanized. Magnetic resonance imaging, arthroscopy, gross pathologic evaluation of the joint, histology, immunohistochemistry, and biomechanical analyses were performed. Generalized linear mixed models (with horse as random effect) were utilized to assess outcome parameters. When P values were <.05, pairwise comparisons were made using least squares means. Results: Improved functional outcome parameters were observed for the treatment group, even though mildly increased joint effusion and subchondral bone sclerosis were noted on imaging. Microscopically, treatment resulted in improvement of several histologic parameters and overall quality of repaired tissue. Proteoglycan content based on safranin O–fast green staining was also significantly higher in the treated defects. Conclusion: Trypsin treatment combined with functionalized hydrogel resulted in improved microfracture augmentation. Clinical Relevance: Therapeutic strategies for microfracture augmentation, such as those presented in this study, can be cost-effective ways to improve cartilage healing outcomes, especially in more active patients.

Chondrogenesis induced in vivo by gene-activated hydrogel based on hyaluronic acid and plasmid DNA encoding VEGF

Development of effective methods for cartilage tissue repair is highly relevant for surgical practice. One of the promising approaches in this area is the use of gene-activated materials that capable to change the production of certain factors involved in reparative chondrogenesis regulation in the damaged area within a certain time. In this study, we developed two gene-activated hydrogels based on hyaluronic acid delivering plasmid DNA encoding vascular endothelial growth factor (VEGF-A) gene. One of the hydrogels also contained octacalcium phosphate microgranules. The materials were implanted into the defects of cranial bones, articular and auricle cartilages in rabbits. Control groups consisted of the same materials without plasmid DNA. We found that gene-activated materials formed a larger volume of cartilaginous tissue with complete restoration of the auricle by 90 days. Healing of the articular cartilage and subchondral bone was also more efficient at the 30 and 60 days follow-up, but by 90 days, remodeling of the newly formed cartilage into fibroelastic and fibrous connective tissues was observed in all groups. Cranial bone defects were filled with newly formed bone tissue in the test group by day 90, while in the control a residual defect filled by fibrous connective tissue was retained. Thus, developed variants of the gene-activated hydrogels are promising candidates to be medical devices for treatment of patients with bone and cartilage pathology.

Do NSAIDs Really Interfere with Healing after Surgery?

Perioperative analgesia should be multimodal to improve pain relief, reduce opioid use and thereby adverse effects impairing recovery. Non-steroidal anti-inflammatory drugs (NSAIDs) are an important non-opioid component of this approach. However, besides potential other adverse effects, there has been a longstanding discussion on the potentially harmful effects of NSAIDs on healing after surgery and trauma. This review describes current knowledge of the effects of NSAIDs on healing of bones, cartilage, soft tissue, wounds, flaps and enteral anastomoses. Overall, animal data suggest some potentially harmful effects, but are contradictory in most areas studied. Human data are limited and of poor quality; in particular, there are only very few good randomized controlled trials (RCTs), but many cohort studies with potential for significant confounding factors influencing the results. The limited human data available are not precluding the use of NSAIDs postoperatively, in particular, short-term for less than 2 weeks. However, well-designed and large RCTs are required to permit definitive answers.

Recombinant fibroblast growth factor-18 (sprifermin) enhances microfracture-induced cartilage healing.

Posttraumatic osteoarthritis is a disabling condition impacting the mostly young and active population. In the present study, we investigated the impact of intra-articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of microfracture treatment, a widely used surgical technique to enhance cartilage healing at the site of injury. For this study, we created a cartilage defect and performed microfracture treatment in fetlock joints of 18 horses, treated joints with one of three doses of sprifermin (10, 30, or 100 μg) or with saline, hyaluronan, and evaluated animals functional and structural outcomes over 24 weeks. For primary outcome measures, we performed histological evaluations and gene expression analysis of aggrecan, collagen types I and II, and cartilage oligomeric matrix proteinin three regions of interest. As secondary outcome measures, we examined animals' lameness, performed arthroscopic, radiographic, and computed tomography (CT) scan imaging and gross morphology assessment. We detected the highest treatment benefit following 100 μg sprifermin treatment. The overall histological assessment showed an improvement in the kissing region, and the expression of constitutive genes showed a concentration-dependent enhancement, especially in the peri-lesion area. We detected a significant improvement in lameness scores, arthroscopic evaluations, radiography, and CT scans following sprifermin treatment when results from three dose-treatment groups were combined. Our results demonstrated, for the first time, an enhancement on microfracture outcomes following sprifermin treatment suggesting a cartilage regenerative role and a potential benefit of sprifermin treatment in early cartilage injuries.