Autologous cultured chondrocytes (Vericel)

骨关节炎（OA）是临床常见的慢性退行性关节病变，衰老、肥胖、劳损、外伤、关节发育异常等因素，都可能引发关节软骨的退行性损伤。据统计，到2022年，OA已成为全球第四大致残性疾病。而关节表面的透明软骨组织既无神经分布，也无血管供应，自我修复与再生能力极弱，一旦受损往往难以自行恢复。 自1998年Marx团队首次采用PRP复合移植骨修复下颌骨缺损后，PRP逐步拓展应用于口腔、整形、骨科、耳鼻喉等多个领域的组织修复，至今已积累了多年临床应用经验。本期内容，我们将解析PRP的独特价值，同时揭秘PRP与MSC（间充质干细胞）联合应用时，在膝骨关节炎治疗中创造的修复奇迹。 问 PRP是什么？ 含义 PRP是“富血小板血浆（Platelet-rich plasma）”的英文缩写，是通过梯度离心技术从自体血液中提取的血浆制品，其核心成分是高浓度的血小板、白细胞与纤维蛋白。经激活处理后，PRP可释放多种生物活性生长因子。 它还有PRC（富血小板浓缩液）、APG（自体血小板凝胶）、PRGF（富含生长因子血浆）等别称，但“PRP”仍是临床与研究中最常用的名称。 简言之，PRP是富含自体高浓度血小板及多种生长因子的血浆制剂。 问 PRP作用机理 机制 PRP的修复效能，源于高浓度血小板所释放的“超生理剂量生长因子+生物活性蛋白”——包括胰岛素样生长因子、血管内皮生长因子、转化生长因子-β（TGF-β）、成纤维生长因子（FGF）等多种活性物质。 这些成分可协同促进自体组织细胞的迁移、增殖与分化，增强低愈合潜能组织的修复能力，最终实现创伤修复与老化损伤组织的功能改善。 问 PRP遇上MSCs “双强组合” 间充质干细胞（MSCs）具备自我更新与多向分化潜能，不仅可直接分化为软骨细胞修复损伤组织，还能抑制炎症因子释放，并通过“归巢效应”靶向聚集于损伤部位，是膝骨关节炎治疗中理想的“种子细胞”。 而PRP作为自体来源的生物制剂，富含TGF-β、血小板衍生生长因子等软骨修复相关因子，可通过以下方式与MSCs协同：为MSCs提供适宜的局部微环境（促进血供、减轻炎症）、促进软骨基质合成，最终显著提升MSCs治疗膝骨关节炎的临床疗效。 问 PRP对膝骨关节炎的作用 作用 1. 促进软骨修复 PRP释放的生长因子可激活软骨细胞活性，推动软骨基质合成与软骨组织再生； 2. 改善临床症状 有效缓解关节疼痛、僵硬等不适，提升关节活动度与患者生活质量； 3. 抑制氧化应激 激活成骨细胞的抗氧化通路，减少活性氧对细胞的损伤，助力软骨重塑与局部神经血管生成； 4. 调控间充质干细胞的功能 PRP可增强间充质干细胞（MSC）的活性，促进其向成骨、成软骨细胞定向分化，精准修复软骨损伤。 问 临床试验与应用进展：从国际到海南博鳌的落地实践 实验与进展 1. 国际成熟经验铺垫 临床研究表明，将人脐带来源的间充质干细胞关节腔内注射，可有效改善退行性膝骨关节炎患者的关节功能与生活质量： • 2012年1月，韩国获批的干细胞药物Cartisem（含脐带间充质干细胞与透明质酸钠），用于治疗退行性OA与软骨损伤，上市后已完成5000余例患者治疗，有效率达97.67%； • 2016年，美国FDA批准干细胞药物Maci上市，用于膝关节软骨损伤的修复治疗，截至2024年，全球已有超3万名患者接受该疗法，术后1年关节功能评分平均提升40%； 2. 海南博鳌：国内“先行先试”的重要阵地 作为我国医疗对外开放的“试验田”，海南博鳌乐城国际医疗旅游先行区已率先开展PRP+干细胞联合治疗膝骨关节炎的临床应用，为国内患者提供与国际同步的治疗方案： • 2023年6月，博鳌超级医院骨科中心启动“自体脂肪间充质干细胞+PRP联合治疗膝骨关节炎”临床项目，截至2024年底，已累计收治120余例患者，患者平均年龄58岁，多为“保守治疗无效、不愿手术置换”的中重度OA患者； • 该项目采用“微创提取+联合注射”模式：从患者腹部提取少量脂肪，分离培养间充质干细胞，与自体PRP混合后，通过关节腔注射给药，全程仅需局部麻醉，术后24小时即可下床活动； • 临床随访数据显示：术后3个月，89%的患者膝关节疼痛评分（VAS）从术前的7-8分（重度疼痛）降至2-3分（轻度疼痛），关节活动度平均增加35°；术后6个月，通过磁共振（MRI）可观察到软骨缺损区有新生软骨组织形成，其中62%的患者恢复正常行走、上下楼梯等日常活动。 2025年关键突破 一、核心机制突破：2025年《Nature Biotechnology》研究证实：PRP先释放TGF-β清除炎症、搭建血管支架，72小时内为干细胞外泌体创造“修复场”；随后外泌体携带Wnt蛋白激活细胞再生，4-8周完成功能化组织重建，协同效应较单一疗法提升2.1倍。 二、临床突破 1. 骨关节炎：PRP联合干细胞外泌体使软骨厚度恢复率达78.3%，患者疼痛指数下降67%，北京协和等5家医院已开展临床试验，AI采血、超声精准注射等技术优化治疗流程。 2. 卵巢功能衰退：西班牙IVIRMA中心研究显示，145名患者经“干细胞动员+PRP卵巢注射”后，68.3%实现卵泡再生，21.2%获得妊娠（含自然妊娠），无严重不良反应。 3. 慢性创面：Ⅲ期压疮患者经联合疗法治疗47天创面愈合，疼痛下降80%，12个月无复发，愈合速度较传统方法快2-3倍。 三、政策与落地 国家卫健委将“干细胞联合生物因子修复”纳入重点专项，聚焦骨关节炎等12类慢病；海南博鳌明确干细胞相关治疗定价，推动技术规范化落地。 关 注 泰 生 源 （ 了解更多关于细胞疗法和我们的技术 ）

Total Revenue Growth of 20% to $63.2 Million, with MACI Revenue Growth of 21% to $53.5 Million Gross Margin Increased More than 400 Basis Points to 74% Adjusted EBITDA Growth of 112% to $13.4 Million, with Adjusted EBITDA Margin Increase of More than 900 Basis Points to 21% Approximately 600 MACI Arthro Surgeons Trained to Date Received FDA IND Clearance for Phase 3 MACI Ankle Clinical Study Conference Call Today at 8:30am Eastern Time CAMBRIDGE, Mass., July 31, 2025 (GLOBE NEWSWIRE) -- Vericel Corporation (NASDAQ:VCEL), a leader in advanced therapies for the sports medicine and severe burn care markets, today reported financial results and business highlights for the second quarter ended June 30, 2025. Second Quarter 2025 Financial Highlights Total net revenue of $63.2 millionMACI® net revenue growth of 21% to $53.5 millionBurn Care net revenue of $9.8 million, consisting of $8.6 million of Epicel® revenue and $1.2 million of NexoBrid® revenueGross margin of 74%, an increase of more than 400 basis points versus the prior yearNet loss of $0.6 million, or $0.01 per diluted shareNon-GAAP adjusted EBITDA increased 112% to $13.4 million, with adjusted EBITDA margin increase of more than 900 basis points to 21%Operating cash flow of $8.2 millionAs of June 30, 2025, the Company had approximately $164 million in cash and investments, and no debt Business Highlights and Updates Record second quarter total revenue and MACI revenueSecond highest number of MACI biopsies in a quarter since launch, with second highest number of biopsies in any month in AprilApproximately 600 MACI Arthro™ surgeons trained to dateMACI implants for the treatment of small femoral condyle defects increased more than 40% in the second quarter versus prior yearMACI sales force expansion accelerated into the second half of 2025 based on MACI Arthro launch indicators and expected MACI implant growthHighest number of Epicel biopsies in a quarter since 2023, representing 38% growth versus prior year, and the highest number of Epicel biopsies in a month in JuneNexoBrid second quarter revenue increased 52% versus the prior yearHighest number of NexoBrid hospital unit orders in any month since launch in JuneReceived FDA IND clearance for MACI Ankle™ clinical study and remain on track to initiate the study in the second half of 2025 “The Company delivered another quarter of solid financial and business results in the second quarter, with significant revenue growth and even higher profitability growth and margin expansion as well as continued strength in the key performance indicators for the MACI Arthro launch,” said Nick Colangelo, President and CEO of Vericel. “Based on the positive trends across the business to start the third quarter, we expect continued strong revenue growth and profitability for the remainder of the year and beyond.” 2025 Financial Guidance Reaffirmed MACI full-year revenue growth in the low 20% rangeUpdated Burn Care revenue guidance for the second half of 2025 to be in line with recent run rate of approximately $10 million per quarterReaffirmed full-year profitability guidance of gross margin of 74% and adjusted EBITDA margin of 26% Second Quarter 2025 ResultsTotal net revenue for the quarter ended June 30, 2025 increased to $63.2 million, compared to $52.7 million in the second quarter of 2024. Total net product revenue for the quarter included $53.5 million of MACI (autologous cultured chondrocytes on porcine collagen membrane) net revenue, $8.6 million of Epicel (cultured epidermal autografts) net revenue, and $1.2 million of NexoBrid (anacaulase-bcdb) net revenue, compared to $44.1 million of MACI net revenue, $7.8 million of Epicel net revenue, and $0.8 million of NexoBrid net revenue, respectively, in the second quarter of 2024. Gross profit for the quarter ended June 30, 2025 was $46.6 million, or 74% of net revenue, compared to $36.6 million, or 70% of net revenue, for the second quarter of 2024. Total operating expenses for the quarter ended June 30, 2025 were $48.6 million, compared to $42.6 million for the same period in 2024. The increase in operating expenses was primarily due to increased headcount and related employee expenses and additional costs related to the Company’s new Burlington facility, including depreciation and MACI tech transfer activities. Net loss for the quarter ended June 30, 2025 was $0.6 million, or $0.01 per diluted share, compared to $4.7 million, or $0.10 per diluted share, for the second quarter of 2024. Non-GAAP adjusted EBITDA for the quarter ended June 30, 2025 was $13.4 million, or 21% of net revenue, compared to $6.3 million, or 12% of net revenue, for the second quarter of 2024. A table reconciling non-GAAP measures is included in this press release for reference. As of June 30, 2025, the Company had approximately $164 million in cash and investments, and no debt. Conference Call Information Today’s conference call will be available live at 8:30 a.m. Eastern Time. The live webcast can be accessed on the Investor Relations section of the Vericel website at http://investors.vcel.com/events-presentations. Presentation slides for the conference call will be available on the webcast and on the website. A replay of the webcast will be available until July 31, 2026. To participate by telephone, dial 855-303-0072 or +1 773-305-6837 if connecting from outside the U.S. When connected, please use passcode: 276790. About Vericel CorporationVericel is a leading provider of advanced therapies for the sports medicine and severe burn care markets. The Company combines innovations in biology with medical technologies, resulting in a highly differentiated portfolio of innovative cell therapies and specialty biologics that repair injuries and restore lives. Vericel markets three products in the United States. MACI (autologous cultured chondrocytes on porcine collagen membrane) is an autologous cellularized scaffold product indicated for the repair of symptomatic, single or multiple full-thickness cartilage defects of the knee with or without bone involvement in adults. Epicel (cultured epidermal autografts) is a permanent skin replacement for the treatment of patients with deep dermal or full thickness burns greater than or equal to 30% of total body surface area. Vericel also holds an exclusive license for North American rights to NexoBrid (anacaulase-bcdb), a biological orphan product containing proteolytic enzymes, which is indicated for eschar removal in adults and pediatric patients with deep partial-thickness and/or full-thickness thermal burns. For more information, please visit www.vcel.com. Epicel® and MACI® are registered trademarks of Vericel Corporation. NexoBrid® is a registered trademark of MediWound Ltd. and is used under license to Vericel Corporation. © 2025 Vericel Corporation. All rights reserved. GAAP v. Non-GAAP MeasuresVericel’s reported earnings are prepared in accordance with generally accepted accounting principles in the United States, or GAAP, and represent earnings as reported to the Securities and Exchange Commission. Vericel has provided in this release certain financial information that has not been prepared in accordance with GAAP. Vericel’s management believes that the non-GAAP adjusted EBITDA described in this release, which includes adjustments for specific items that are generally not indicative of our core operations, provides additional information that is useful to investors in understanding Vericel’s underlying performance, business and performance trends, and helps facilitate period-to-period comparisons and comparisons of its financial measures with other companies in Vericel’s industry. However, the non-GAAP financial measures that Vericel uses may differ from measures that other companies may use. Non-GAAP financial measures are not required to be uniformly applied, are not audited and should not be considered in isolation or as substitutes for results prepared in accordance with GAAP. Forward-Looking StatementsVericel cautions you that all statements other than statements of historical fact included in this press release that address activities, events or developments that we expect, believe or anticipate will or may occur in the future are forward-looking statements. Although we believe that we have a reasonable basis for the forward-looking statements contained herein, they are based on current expectations about future events affecting us and are subject to risks, assumptions, uncertainties and factors relating to our operations and business environment, all of which are difficult to predict and many of which are beyond our control. Our actual results may differ materially from those expressed or implied by the forward-looking statements in this press release. These statements are often, but are not always, made through the use of words or phrases such as “anticipates,” “intends,” “estimates,” “plans,” “expects,” “continues,” “believe,” “guidance,” “outlook,” “target,” “future,” “potential,” “goals” and similar words or phrases, or future or conditional verbs such as “will,” “would,” “should,” “could,” “may,” or similar expressions. Among the factors that could cause actual results to differ materially from those set forth in the forward-looking statements include, but are not limited to, uncertainties associated with our expectations regarding future revenue, growth in revenue, market penetration for MACI®, MACI Arthro™, Epicel®, and NexoBrid®, growth in profit, gross margins and operating margins, the ability to continue to scale our manufacturing operations to meet the demand for our cell therapy products, including the timely qualification of a new manufacturing facility in Burlington, Massachusetts, the ability to sustain profitability, contributions to adjusted EBITDA, the expected target surgeon audience, potential fluctuations in sales and volumes and our results of operations over the course of the year, timing and conduct of clinical trial and product development activities, timing and likelihood of the FDA’s potential approval of the use of MACI to treat cartilage defects in the ankle, the estimate of the commercial growth potential of our products and product candidates, competitive developments, changes in third-party coverage and reimbursement, including recent and future healthcare reform measures and private payor initiatives, surgeon adoption of MACI Arthro, physician and burn center adoption of NexoBrid, labor strikes, supply chain disruptions or other events or factors that might affect our ability to manufacture MACI or Epicel or affect MediWound’s ability to manufacture and supply sufficient quantities of NexoBrid to meet customer demand, including but not limited to the ongoing and evolving conflicts in the Middle East region involving Israel, negative impacts on the global economy and capital markets resulting from the conflict in Ukraine and the ongoing and evolving Middle East conflicts, including those associated with potential further involvement by the U.S., changes in trade policies and regulations, including the potential for increases or changes in duties, current and potentially new tariffs or quotas, lingering effects of adverse developments affecting financial institutions, companies in the financial services industry or the financial services industry generally, possible changes in governmental monetary and fiscal policies, including, but not limited to, Federal Reserve policies in connection with continued inflationary pressures, the impact from future regulatory, judicial and legislative changes to our industry or to the broader business landscape, including those included in the One Big Beautiful Bill Act, global geopolitical tensions and potential future impacts on our business or the economy generally stemming from a public health emergency. These and other significant factors are discussed in greater detail in Vericel’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the Securities and Exchange Commission (SEC) on February 27, 2025, Vericel’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2025, filed with the SEC on July 31, 2025, and in other filings with the SEC. These forward-looking statements reflect our views as of the date hereof and Vericel does not assume and specifically disclaims any obligation to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this release except as required by law. Investor Contact:Eric Burnsir@vcel.com+1 (734) 418-4411 VERICEL CORPORATIONCONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(in thousands, except per share amounts - unaudited) Three Months Ended June 30, Six Months Ended June 30, 2025 2024 2025 2024 Product sales, net $63,240 $52,662 $115,838 $103,943 Total revenue 63,240 52,662 115,838 103,943 Cost of product sales 16,627 16,061 32,952 31,988 Gross profit 46,613 36,601 82,886 71,955 Research and development 6,731 7,363 13,992 13,781 Selling, general and administrative 41,911 35,269 83,715 69,669 Total operating expenses 48,642 42,632 97,707 83,450 Loss from operations (2,029) (6,031) (14,821) (11,495)Other income (expense): Interest income 1,657 1,510 3,314 3,272 Interest expense (157) (153) (310) (306)Other income (expense) (24) (8) 18 (15)Total other income 1,476 1,349 3,022 2,951 Net loss $(553) $(4,682) $(11,799) $(8,544)Net loss per common share: Basic and diluted $(0.01) $(0.10) $(0.24) $(0.18)Weighted-average common shares outstanding: Basic and diluted 50,368 48,686 50,138 48,413 VERICEL CORPORATIONRECONCILIATION OF REPORTED NET LOSS (GAAP)TO ADJUSTED EBITDA (NON-GAAP MEASURE)(in thousands - unaudited) Three Months Ended June 30, Six Months Ended June 30, 2025 2024 2025 2024 Net loss $(553) $(4,682) $(11,799) $(8,544)Stock-based compensation expense 10,140 9,520 21,645 19,354 Depreciation and amortization 2,826 1,323 5,512 2,701 Net interest income (1,500) (1,357) (3,004) (2,966)Pre-occupancy lease expense and tech transfer 2,446 1,509 4,247 2,986 Adjusted EBITDA (Non-GAAP) $13,359 $6,313 $16,601 $13,531 VERICEL CORPORATIONCONDENSED CONSOLIDATED BALANCE SHEETS(in thousands - unaudited) June 30, December 31, 2025 2024ASSETS Current assets: Cash and cash equivalents $80,532 $74,520Restricted cash — 10,529Short-term investments 36,349 41,693Accounts receivable (net of allowance for doubtful accounts of $1 and $10, respectively) 64,290 61,375Inventory 16,831 17,373Other current assets 6,575 7,287Total current assets 204,577 212,777Property and equipment, net 109,848 103,161Intangible assets, net 5,938 6,250Right-of-use assets 67,398 70,098Long-term investments 47,400 39,880Other long-term assets 447 556Total assets $435,608 $432,722LIABILITIES AND SHAREHOLDERS’ EQUITY Current liabilities: Accounts payable $12,857 $23,848Accrued expenses 14,404 17,065Current portion of operating lease liabilities 13,753 9,257Other current liabilities 118 116Total current liabilities 41,132 50,286Operating lease liabilities 86,011 89,593Other long-term liabilities 1,656 876Total liabilities 128,799 140,755Total shareholders’ equity 306,809 291,967Total liabilities and shareholders’ equity $435,608 $432,722